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Brand Names Drove Differences in Part D Spending

Wed, 08 Feb 2012 22:00 GMT

BY MARY ANN MOON
Elsevier Global Medical News
Breaking News

Most of the wide geographic variation in Medicare spending for prescription drugs is due to the cost of the drugs selected rather than to the volume of drugs used in each region, according to a report in the Feb. 9 issue of the New England Journal of Medicine.

The choice of brand-name drugs rather than generics accounts for approximately 76% of this variation. If the geographic areas with the highest drug spending had used generics as often as those with the lowest drug spending in 2008, Medicare and its beneficiaries would have saved $4.5 billion that year, said Julie M. Donohue, Ph.D., of the University of Pittsburgh and her associates.

A considerable variation in prescription-drug spending was reported in 2010, but the reasons for that variation were not identified. Some speculated that costs were higher in regions with the most patients or the most seriously ill patients than regions with fewer patients or less seriously ill patients.

Dr. Donohue and her colleagues analyzed data on 4,666,866 Part D beneficiaries in 2008. They assessed spending for three classes of drugs commonly used by the elderly for which there are no over-the-counter substitutes and which together account for nearly one-fourth of all drug spending annually: ACE inhibitors and ARBs, statins, and newer antidepressants (SSRIs and SNRIs).

After adjustment for demographic, socioeconomic, and health-status differences among the 306 geographic regions studied, per capita prescription-drug spending varied by 25% from the area with the lowest drug spending ($2,413 per patient) to that with the highest ($3,008 per patient).

Overall, most (76%) of the regional variation was ascribed to the cost per prescription filled, and the remaining 24% was ascribed to differences in volume. However this pattern differed among the three drug categories studied, the investigators said (N. Engl. J. Med. 2012;366:530-8).

For ACE inhibitors and ARBs, 90% of the variation in costs was due to the use of brand-name ARBs, which had no generic equivalents during the study period. For statins, 56% of the variation was due to the use of brand-name rather than generic drugs.

But for antidepressants, only about 36% of the variation was due to the use of brand-name rather than generic drugs. Most of the variation instead was due to wide differences in the volume of SSRIs and SNRIs used in various areas of the country. The highest-use areas filled nearly 30% more prescriptions per capita for these antidepressants than did the lowest-use areas.

Some areas of the country consistently used a high percentage of brand-name drugs, while others consistently used a high percentage of generics. For example, in Miami, patients almost always were prescribed brand-name ACE inhibitors, ARBs, statins, SSRIs, and SNRIs, while patients in Rochester, Minn., rarely were prescribed brand-name drugs in any of these categories.

If the regions in the highest quintile of prescription-drug spending had used the same number of generics as those in the lowest quintile of spending, “we estimate that overall Part D drug spending would have been 10% lower in 2008.” This translates into a nationwide savings of $4.5 billion just for Medicare and its beneficiaries, Dr. Donohue and her associates noted.

This study was supported by the National Institute on Aging, the Agency for Healthcare Research and Quality, the National Institute of Nursing Research, the National Institute of Mental Health, the Robert Wood Johnson Foundation, and the Veterans Affairs Health Services Research and Development Service. No relevant financial conflicts of interest were reported.

Subject Codes:
top_stories; mental_health; general_primary; cardiology; gerontology;

http://www.imng.com

February 08, 2012 05:00 PM EST

Framingham Score Flags MI Risk After Stroke

Tue, 07 Feb 2012 21:18 GMT

BY MITCHEL L. ZOLER
Elsevier Global Medical News
Breaking News

NEW ORLEANS (EGMN) – An elevated Framingham Risk Score identified recent ischemic stroke patients at high risk for a myocardial infarction or vascular death over the next 2 years, in a retrospective analysis of data from more than 2,500 stroke survivors without documented coronary heart disease.

If prospective study results confirm this finding, it could establish the Framingham Risk Score (FRS) as an important prognostic assessment for patients with a recent ischemic stroke, Dr. Amytis Towfighi said at the International Stroke Conference. If used this way, the FRS could identify stroke survivors who would benefit from more intensive risk-factor modification, she said.

“Considering every stroke to be a coronary risk equivalent could expose patients with a low risk for subsequent coronary events to unnecessary treatment,” said Dr. Towfighi, a neurologist at the University of Southern California in Los Angeles and director of the acute neurology/acute stroke unit at Rancho Los Amigos National Rehabilitation Center in Downey, Calif.

“Unlike coronary atherosclerosis, there are lots of different causes of stroke, including nonatherosclerotic mechanisms.

“Many stroke survivors harbor asymptomatic coronary heart disease, and beyond the acute period they are often at higher risk for cardiac death than for recurrent cerebrovascular events,” she said. Identifying patients with high FRSs of 20% or greater could flag those who would benefit from treatment with a beta- blocker; coronary diagnostic imaging; coronary revascularization; or more intensive vascular risk reduction by reducing body mass index, lowering triglycerides, exercising tighter diabetes management, and smoking cessation.

“Today, the FRS is usually not calculated for stroke patients,” Dr. Towfighi said in an interview. “Part of the issue is that the FRS was initially developed for people who had not yet had a [cardiovascular] event, so it has not been studied in patients who had a stroke. We didn’t know going into our study whether or not a high FRS would predict a myocardial infarction or vascular death in patients who had a stroke.”

To test whether the FRS could help stratify coronary risk in stroke patients, Dr. Towfighi and her associates analyzed data collected from 3,509 patients who had a recent ischemic stroke and who participated in the Vitamin Intervention for Stroke Prevention trial during 1996-2003 (JAMA 2004;291:565-75). The analysis primarily focused on the 2,547 patients from this group who did not have documented coronary heart disease at the time of their enrollment.

Calculation of the FRS for these patients identified 933 (37%) with a score of 20% or greater, and 1,614 (63%) with a score of less than 20%.

The researchers then tallied the rates of myocardial infarction, vascular death, or stroke in these two subgroups during 2 years of follow-up, and compared the rates between the two FRS groups in a multivariate analysis that controlled for baseline differences in age, race, prior stroke, body mass index, heart failure, carotid endarterectomy, stroke severity, alcohol use, low-density lipoprotein cholesterol, triglyceride levels, mean systolic blood pressure while in the study, antidyslipidemia drug treatment, antithrombotic drug treatment.

In this analysis, patients with an FRS of 20% or greater at baseline had a 2.8-fold increased risk for a myocardial infarction during 2 years of follow-up compared with patients with a lower FRS. The risk of vascular death during follow-up was 80% higher in the high-FRS subgroup than in patients with a lower score. However, a higher FRS had no link with an increased risk for a subsequent stroke.

In addition, the FRS components most strongly linked to subsequent myocardial infarction risk were smoking, which raised the risk by 70%, and diabetes, which doubled the risk.

These findings are not conclusive because they came from a retrospective analysis and may have been influenced by unmeasured confounding. Ideally, the findings need confirmation in a prospective study, Dr. Towfighi said.

Despite this limitation, Dr. Towfighi noted that she and her associates at Rancho Los Amigos now calculate an FRS for their stroke patients “because we feel it’s useful,” she said at the meeting, which was sponsored by the American Heart Association.

Dr. Towfighi said that she had no disclosures.

Subject Codes:
cardiology; neurology;

http://www.imng.com

February 07, 2012 04:18 PM EST

Dr. Amytis Towfighi

Bread and Lunch Meats Top List of Sodium Sources

Tue, 07 Feb 2012 19:58 GMT

BY HEIDI SPLETE
Elsevier Global Medical News
Breaking News

Nearly half of Americans’ sodium consumption can be traced to 10 types of foods, according to data from the Centers for Disease Control and Prevention published Feb. 7 in the CDC’s Morbidity and Mortality Weekly Report.

The top 10 sources, which account for 44% of sodium consumption in Americans over age 2 years, are white bread and rolls; lunch meats, including deli turkey and ham; pizza (frozen or restaurant); poultry; soups; sandwiches; cheese; meat dishes; pasta dishes: and salty snack foods such as potato chips, pretzels, and popcorn.

Some 90% of Americans eat too much sodium, which increases their risk for developing high blood pressure, which in turn can increase the risk for heart disease and stroke, CDC Director Dr. Thomas R. Frieden said in a media telebriefing.

“One of the things that is driving our blood pressure up is that most of the adults in this country eat or drink twice the amount of sodium that is recommended,” Dr. Frieden said. Most of that comes from sodium already present in food, not what is added at the table, he noted.

According to the CDC report, the average American older than 2 years consumes 3,300 mg of sodium daily from food alone, not including any salt added at the table. The U.S. Dietary Guidelines recommendation is less than 2,300 mg/day, and only 1,500 mg/day for individuals at increased risk for heart disease and stroke: adults aged 51 years and older; individuals with high blood pressure, diabetes, or chronic kidney disease; and African Americans.

Foods that seem nutritious may have high levels of sodium, such as cottage cheese or turkey breast from a deli.

“Potato chips, pretzels, and popcorn only account for about 3% of sodium consumption,” Dr. Frieden said.

Overall, 65% of Americans’ sodium intake comes from food sold in grocery stores and 25% comes from restaurant foods, he said.

Cutting back on sodium is a challenge because it is present in so many processed foods and restaurant foods, said Dr. Frieden. However, the sodium content of processed foods can vary widely by brand, so simply reading the labels and comparing products is an easy way to cut down on sodium. The sodium in a single piece of pizza can vary as much as two or three times, depending on the brand, he said. Eating more fresh or frozen fruits and vegetables (without sauces) can curb sodium consumption, as can preparing more food at home instead of eating out or eating processed foods, he said.

Physicians can play an important role in helping everyone reduce their sodium intake, especially those at increased risk for heart disease and stroke.

“Physicians can work with nutritionists and other health professionals to help patients understand what the sources of sodium are in their own diets,” Dr. Frieden explained. “They may be surprised to find that their breakfast cereal contains the equivalent of 8-10 shakes of salt,” he said.

Individuals may find options for cereals, meals, and snacks that contain much less sodium and taste just as good, said Dr. Frieden. “We encourage salting to taste,” by adding minimal salt at the table rather than consuming products that are already high in salt, and by using alternatives to salt to flavor food, he said. “There are plenty of spices other than sodium that can make food taste great,” he added.

Some companies are already working to gradually reduce the salt in processed foods. A report issued last year by the Institute of Medicine recommended that food manufacturers gradually reduce the amount of sodium in their products.

This process will take time, but the goal is to improve consumer choices, said Dr. Frieden.

“The bottom line is that heart disease and stroke are leading causes of health care spending in this country, and it is possible to reduce that by reducing the sodium in our diets,” Dr. Frieden emphasized.

“We can substantially reduce sodium intake, save lives, and save money,” he said.

The data were taken from “What We Eat in America,” part of the national Health and Nutrition Examination Survey, 2007-2008.

For guidance on a low-sodium eating plan, visit the National Institutes of Health’s website for the DASH diet.

Subject Codes:
top_stories; general_primary; cardiology;

http://www.imng.com

February 07, 2012 02:58 PM EST

Thomas R. Frieden

Perspective: The Role of CABG

Tue, 07 Feb 2012 17:36 GMT

BY WILLIAM E. GOLDEN, M.D., AND ROBERT H. HOPKINS, M.D.
Elsevier Global Medical News

Background

Evolving techniques and better understanding of coronary artery disease have changed outcomes for patients with severe coronary artery disease over the last two decades. The American College of Cardiology Foundation recently published an evidence-based reassessment of the role of coronary bypass surgery to guide clinical decision making.

Conclusions

CABG is associated with substantially less need for revascularization than is percutaneous coronary intervention (PCI) during the first year after intervention (less than 5% vs. nearly 25%). This advantage persists through year 5 (10% vs. 45%). Diabetics, in particular, have better survival after CABG as compared to PCI.

While PCI reduces angina, it has not been shown to improve survival or reduce MI in patients without recent acute coronary syndromes. Meta-analyses have not shown superior survival of bare metal stent over balloon angioplasty interventions. Similarly, drug eluting stents have not resulted in superior survival over bare metal stents.

Internal mammary artery grafts have a greater than 90% patency 10 years after CABG with only 1% demonstrating significant atherosclerotic stenosis.

Bilateral internal mammary artery grafts can improve cardiovascular outcomes but are associated with higher rates of sternal wound infections in obese and diabetic patients.

Up to 25% of saphenous vein grafts occlude in the first postoperative year, and annual occlusion rates thereafter are 1%-2% until year 5 and 4%-5% from years 5-10. After 10 years, half of saphenous vein grafts are patent, of which 50% demonstrate atherosclerosis.

Radial arteries are more muscular and prone to spasm unless used for left-sided lesions with more than 70% blockage.

On-pump CABG has better 1-year patency and equivalent neuropsychiatric outcomes with similar resource use when compared with off-pump procedures.

Inhalational anesthetics improve intracardiac blood flow and are associated with quicker extubation recovery times than is a narcotic-based regimen.

The left internal mammary artery should be used to bypass the left anterior descending unless there are contraindications, such as previous radiation injury or specific limitations to blood flow.

Because lower flow rates are associated with greater graft occlusion, arterial grafts should not be used for right coronary artery bypass unless there is a critical stenosis.

Coronary stenting should not be performed in patients who cannot adhere to or tolerate dual antiplatelet therapy (DAPT) because of the high risk of rethrombosis and related mortality: At least 30 days for bare metal stents and a year for drug eluting stents.

Aspirin, 100 to 325 mg a day, should be given throughout the perioperative period to improve outcomes with a minimal risk of bleeding. Postoperative aspirin, started within 6 hours of surgery, improves saphenous vein graft patency. Doses less than 100 mg, while efficacious for patients with coronary disease, are less efficacious for sustaining saphenous vein patency.

Thienopyridines such as clopidogrel and ticagrelor should be stopped preferably 5 days before CABG, but definitely 24 hours prior to surgery to avoid risk of hemorrhage. Prasugrel should be stopped at least 7 days preoperatively.

All patients should receive statin therapy perioperatively. Patients not on statin therapy have been shown to sustain higher rates of post-CABG cardiovascular complications.

Diabetic patients should receive postoperative continuous infusion insulin to keep blood glucose under 180 mg/dL. Targeting glucose levels under 140 mg/dL has uncertain value at the present time.

Perioperative beta-blocker administration reduces the incidence and impact of CABG-related atrial fibrillation. Acute and chronic beta-blocker administration favorably affects the reduction ofon reducing ischemia and mortality.

Epiaortic ultrasound is superior to palpation or transesophageal echo to detect location and severity of ascending aorta atherosclerosis that can pose a risk for perioperative stroke in CABG patients.

CABG should not be performed on patients with sustained ventricular tachycardia associated with myocardial scars but without evidence of current ischemia.

All patients should be considered for postoperative cardiac rehabilitation. A 3-month course of rehabilitation activities three times a week starting after the first month postoperatively can increase exercise tolerance by one-third.

Reference

2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines

(Circulation 2011;124: e652-e735).

Dr. Golden is professor of medicine and public health, and Dr. Hopkins is program director for the internal medicine/pediatrics combined residency program at the University of Arkansas, Little Rock. Write to Dr. Golden and Dr. Hopkins at imnews@elsevier.com. They reported having no conflicts of interest.

This column, “The Effective Physician,” appears regularly in Internal Medicine News, a publication of Elsevier.

Subject Codes:
cardiology;

http://www.imng.com

February 07, 2012 12:36 PM EST

William E. Golden (left) and Robert H. Hopkins

Community Hospital Offers Catheter-Directed Pulmonary Thrombolysis

Mon, 06 Feb 2012 21:53 GMT

BY SHERRY BOSCHERT
Elsevier Global Medical News
Breaking News

Few, if any, vascular specialists are aggressively treating massive or submassive pulmonary embolism with catheter-directed thrombolytic therapy at community hospitals, but it is feasible and can have good outcomes with proper planning and preparation, according to Dr. Jeffrey Y. Wang.

Catheter-directed thrombolytic therapy for massive or submassive pulmonary embolism (PE) can shorten stays in the ICU and the hospital, reduce or eliminate the need for home oxygen therapy, and help restore right heart function, he said. However, catheter-directed interventions for these patients is rare outside of academic or tertiary-care settings, probably because of a lack of randomized trials, little retrospective data, and lack of expertise, he said.

For physicians considering this treatment at their own community hospitals, Dr. Wang emphasized that preparing the hospital and protocols are as important as is technical expertise in doing the procedure. The fluoroscopy suite must be available on an emergency basis, for example.

“In our institution, we use the same protocols for call-in and transport to the cath lab as for ST-elevation myocardial infarction, which allows us to get the patient up and into the fluoroscopy suite within 30 minutes,” said Dr. Wang of Shady Grove Adventist Hospital, Rockville, Md.

Before doing his first case, he made sure that protocols were in place in the emergency department, in the ICU, and with the hospitalist team for the early detection of deep vein thrombosis and PE, notification of the appropriate staff, and posttreatment care of patients.

Systemic anticoagulation has been the mainstay of treatment for PE, but the American Heart Association and the American College of Chest Physicians have recommended more aggressive therapy for massive and submassive PEs, Dr. Wang said. Up to 60% of patients with massive PE die, data suggest, with two-thirds of the deaths occurring in the first hour of embolism formation. Within 30 days of submassive PE formation, 15%-20% of patients die secondary to pulmonary hypertension and subsequent cor pulmonale.

Approximately 30% of all 500,000 symptomatic PEs diagnosed each year in the United States lead to death. Even among inpatients who are diagnosed with a PE while in the hospital, the mortality rate is approximately 10%-15%, he said.

Until recently, there was no Food and Drug Administration–approved device for catheter-directed thrombolytic therapy. “There’s also not a purpose-built device to help you with these types of procedures,” Dr. Wang said.

At the annual meeting of the Southern Association for Vascular Surgery, he described treating nine women and three men who had a total of seven massive and five submassive PEs. Catheter-directed thrombolytic therapy was offered to patients with massive or submassive PE if they were hemodynamically unstable or had right heart dysfunction, elevated troponin levels, or pulmonary artery pressures greater than 70 mm Hg, or if they were not being weaned off intubation for oxygen within 5 days, Dr. Wang said. He excluded patients who were actively bleeding or who were not able to tolerate any systemic anticoagulation – “not even aspirin,” he said.

Recent surgery was not a disqualifying factor. “Typically those patients were orthopedic in nature, with a hip or knee replacement,” Dr. Wang said. The patient would develop a big PE, and the orthopedist would give him the green light for aggressive treatment.

All procedures were technically successful. One patient developed hemodynamically significant bradycardia, but all were off supplemental oxygen within 24 hours of the procedure, and there were no bleeding events.

One patient died 14 hours after the procedure, most likely due to a paradoxical embolism to the intestine, Dr. Wang said. The 11 surviving patients were discharged to home within 48 hours of the intervention.

His technique includes accessing the internal jugular vein to get to the pulmonary artery, placing a vena cava filter, and giving tissue plasminogen activator as the lytic agent. All patients had a spiral CT scan before going to the catheterization lab, so pulmonary angiography was not routinely performed.

He reserved mechanical (catheter) thrombectomy for some patients with massive thromboembolism. Instead of being guided by angiography, he determined the duration of mechanical thrombectomy by the patient’s blood pressure, pulse, and oxygen saturation.

“I discontinued mechanical thrombectomy once oxygen saturation was above 95%, they’re weaning off their inotropes, and the pulse rate was trending toward normal,” he said.

For some patients who developed nonsinus arrhythmias due to the wire manipulations within the heart and pulmonary arteries, he removed the wire device, waited for it to resolve, and continued. A minority of patients whose arrhythmias continued to occur during the intervention received calcium blockade or beta blockade.

Patients who received mechanical thrombectomy developed dark or bloody urine that resolved within 48 hours with hydration.

Follow-up at 2 weeks assessed general function and access sites, and patients had a repeat echocardiogram at 1 month. If they were doing well functionally and pulmonary hypertension had resolved, Dr. Wang offered to remove the vena cava filter. All but one patient accepted. All were to remain on systemic anticoagulation for 6-12 months, and patients with massive PE underwent hematologic workups.

More Studies Underway of Promising Therapy

“It amazes me that over many decades, the treatment of pulmonary embolism has remained stagnant. There have been no significant changes in the way we treat these patients. Most are treated with systemic anticoagulation and prolonged warfarin therapy,” said discussant Dr. Juan Ayerdi.

“There are many limitations to the use of systemic thrombolysis. The most important one is a high incidence of bleeding complications, about 20%-40%. Surgical thrombectomy also has limitations and is performed in a very limited number of centers, with mortality rates of about 10%-20%,” said Dr. Ayerdi of the Medical Center of Central Georgia, Macon.

“There is no question in my mind that there is a large potential benefit in treating patients with catheter-directed thrombolysis, particularly patients with massive pulmonary embolism. There’s also a potential benefit from catheter-directed thrombolysis in a large subgroup of patients with submassive pulmonary embolism. Those patients may benefit the most in terms of prevention of pulmonary hypertension,” he said.

“Many of these questions are being investigated now in a European prospective, randomized trial comparing catheter-guided pulmonary thrombolysis to chemical thrombolysis. In the Unites States, there are a couple of registries for these patients, and a randomized trial is expected to start in the near future. I encourage vascular specialists to enroll patients in these,” said Dr. Ayerdi.

Dr. Wang and Dr. Ayerdi reported having no financial disclosures.

Subject Codes:
cardiology; surgery;

http://www.imng.com

February 06, 2012 04:53 PM EST

Dr. Jeffrey Y. Wang

Solitaire Trumped Merci in Stroke Clot Retrieval Trial

Sat, 04 Feb 2012 00:13 GMT

BY MICHELE G. SULLIVAN
Elsevier Global Medical News
Breaking News

NEW ORLEANS (EGMN) –An investigational clot-retrieval device completely recanalized blocked cerebral arteries, improved neurologic outcomes, and significantly reduced mortality from acute ischemic stroke more often than did the widely used Merci device in a randomized, open-label trial.

The SWIFT (SOLITAIRE-FR With the Intention for Thrombectomy) study intended to randomize 200 patients with ischemic stroke to treatment with either of the devices, but after 18 months, the trial’s data safety monitoring board stopped the study with 144 patients treated, citing “an overwhelming benefit” of the Solitaire-Flow Restoration device over the Merci device, Dr. Jeffrey Saver said at the International Stroke Conference.

“With these results, we see for the first time a highly effective cerebral recanalization procedure for ischemic stroke,” said Dr. Saver, director of the stroke unit at the University of California, Los Angeles, in an interview. “[Tissue plasminogen activator] opens the arteries partially 40% of the time and completely just 5% of the time. This device opens them completely 60% of the time. It’s a dramatic step forward and a device that will probably be a game-changer for our systems, once it becomes available.”

Solitaire is a columnar metal cage which, when expanded, engages the clot at multiple points, facilitating extraction and decreasing the chance of symptomatic intracranial bleeding. The Merci device, a corkscrew-like coil, does release pressure on the atrial wall, “but has a tendency to uncoil and fail to engage the clot,” he said.

The patients’ average age was 67 years; most (68%) were male. The median pre-stroke modified Rankin Scale score was 0.5. Time to first angiogram was 4-5 hours.

The primary end point – successful recanalization without symptomatic intracranial hemorrhage – occurred in 61% of the Solitaire group and 24% of the Merci group. This was a highly significant difference with a P value of .0001 in both noninferiority and superiority analyses.

The trial’s secondary end points also indicated the superiority and noninferiority of Solitaire in comparison with Merci:

• Use of rescue therapy (21% vs. 44%).

• Symptomatic intracranial hemorrhage (2% vs. 11%).

• All intracranial hemorrhage (17% vs. 38%).

• Good 90-day neurologic outcome (58% vs. 33%).

• 90-day mortality (17% vs. 38%).

The investigators defined a good neurologic outcome as a modified Rankin Scale score of 0-2 if a patient came in at that level, if the patient returned to their baseline score after coming in with a worse score, or for patients who achieved at least a 10-point increase in their National Institutes of Health Stroke Scale score also were assessed as having a good outcome.

The results demonstrate an excellent number-needed-to-treat analysis, Dr. Saver said.

“For every 2.7 patients treated, 1 additional patient had a successful recanalization with no brain bleed. For every five patients treated, one patient was saved from death. And for every four patients treated, there was one more with a good neurologic outcome.”

Device fracture occurred in two instances with Solitaire but in no cases with Merci. There were two instances with each device in which the device could not be delivered appropriately. Air embolism occurred in one patient with each device. Vasospasms occurred in eight cases with Solitaire and six cases with Merci. Two patients undergoing interventions with the Merci device had vessel perforations, compared with none who were treated with the Solitaire device. Distal emboli occurred with Solitaire in two patients and with Merci in three patients.

The study design included a “roll-in” period in which the investigators learned how to perform the interventions; 31 patients were treated during this time, while the remaining 113 were randomized to treatment with the Merci device (55) or the Solitaire (58). All of the patients either were ineligible for tissue plasminogen activator or had failed a treatment.

Each patient received up to three passes of the assigned device. A separate lab, blinded to treatment arms, reviewed scans of the treated arteries. If the clot remained, physicians could try other appropriate treatments.

While SWIFT decisively proved Solitaire’s capability as a clot retriever, it didn’t have the chance to explore the device’s other possible indication as a stent, Dr. Saver added.

‘This device is designed to pull the clot out or, if that fails, you can detach the stent portion and leave it in place. But what we experienced in this study was that it was getting the clot out so often, we weren’t able to test it as a stenting device.”

In fact, for some patients, Solitaire may be more suited as a stent than as a retrieval device. “I think that for a patient who has plaques in the intracranial arteries and a little bit of clot on top of the plaque, retrieval is not the best strategy. The devices tend to snag on the hard edges of the plaque. Those patients are best treated with a stenting approach, which may possible with his device.”

Solitaire has already been approved in Europe. These new data should help propel it to a U.S. approval, he said.

“The data from this trial have been submitted to the Food and Drug Administration, and we are hopeful that within a few weeks or months these results will allow the FDA to approve it in the U.S.”

“This trial brings us into the third generation of new and potentially better devices to open blocked arteries in acute ischemic stroke. Solitaire showed pretty impressive recanalization rates, compared with Merci, and improved clinical and functional outcomes,” according to Dr. Ralph L. Sacco.

“This device also looks at little easier to deploy than Merci, and it seems to be somewhat more practical and better designed,” said Dr. Sacco, immediate past president of the American Heart Association and chairman of neurology at the University of Miami.

“I think the SWIFT trial will bring very important information to the FDA review, and hopefully we will have another device entering the market to help us treat acute stroke.

“But even after interventionists get the Solitaire device, they must be well trained before they start using it. Additionally, devices like this are primarily used in comprehensive stroke centers. To increase the number of patients who might benefit from it, we need to increase the numbers of our comprehensive stroke centers,” Dr. Sacco said.

Ev3, the company that makes Solitaire, funded the SWIFT trial. Dr. Saver disclosed that he is on the company’s speakers advisory board. Dr. Sacco said he had no relevant disclosures.

Subject Codes:
cardiology; neurology;

http://www.imng.com

February 03, 2012 07:13 PM EST

Ralph L. Sacco

Aspirin, Warfarin Show Equal Heart Failure Efficacy

Fri, 03 Feb 2012 21:58 GMT

BY MITCHEL L. ZOLER
Elsevier Global Medical News
Breaking News

NEW ORLEANS (EGMN) – The largest, best controlled comparison of aspirin and warfarin ever done in patients with heart failure showed no overall difference between the two drugs for preventing thromboembolic events that cause death or stroke.

As a consequence, for the time being physicians should feel comfortable prescribing either drug to patients with a left ventricular ejection fraction of 35% or less and in sinus rhythm, Dr. Shunichi Homma reported at the International Stroke Conference. “Most heart failure patients are put on aspirin or warfarin” to deal with their elevated risk for thromboembolic events, said Dr. Homma, a cardiologist and professor of medicine at Columbia University in New York, and until now it’s remained an open question whether one drug surpassed the other. The study compared a daily 325-mg aspirin dosage with a warfarin regimen targeted to maintain patients at a target international normalized ratio (INR) of 2.75.

“Overall, there was no benefit of one over the other” for the study’s primary end point of the combined rate of death, ischemic stroke, or intracerebral hemorrhage, he said in an interview. Aspirin is more convenient and cheaper than a warfarin regimen that requires regular INR monitoring, and the results also showed that aspirin led to significantly fewer hemorrhagic events. In addition, total major hemorrhagic events, including intracranial, intracerebral, and gastrointestinal bleeding, ran 0.9% in the aspirin patients and 1.8% in the warfarin patients, a statistically significant difference.

But findings from the Warfarin Versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) Trial also showed advantages for warfarin. While the primary, combined end point showed a virtual dead heat of a 6.6% event rate with warfarin and a 6.5% rate with aspirin, warfarin treatment showed a statistically significant edge over aspirin for preventing ischemic strokes. This end point occurred in 0.7% of the warfarin patients and in 1.4% of those on aspirin, a significant difference.

In addition, warfarin treatment produced a hard-to-explain advantage for the study’s primary end point that appeared once patients were followed for more than 3 years. Although average follow-up for all 2,305 patients in the study was 3.5 years, follow-up for more than 1,000 of the enrollees extended to 4 years, and nearly 700 patients had a follow-up of 5 years. After 4 years, warfarin produced a statistically significant, roughly 25% reduction in the study’s primary end point compared with aspirin, an advantage maintained through 5 years and then out to 6 years.

Because this separate analysis of the study results after prolonged follow-up was a prespecified end point, it represented a major finding of the trial, although its full interpretation will need additional analysis and its clinical implications are not yet clear, Dr. Homma said.

“While there was no overall difference in the outcomes, there is a group of patients, those followed for 4 or more years, who benefited from warfarin. We don’t know who they are or why this happens. It’s important to find out, before we decide to [routinely use] warfarin,” he said. “Also, in years 1-3 there was no significant difference between the two drugs, and given the bleeding risk with warfarin we need to clarify the characteristics of the patients who might benefit from one medication or the other.”

For the time, being, until a better understanding of the long-term warfarin effect is available, “I think the results of our study will tip physicians toward using aspirin over warfarin,” he said.

“We suspected, based on prior results, that there might be a change in the effect [of warfarin] over time,” said J.L.P. Thompson, Ph.D., professor of clinical biostatistics and clinical neurology at Columbia and co-principal investigator on the study. “The benefit from warfarin is modest, but it is there. It does not lead to a clinical recommendation at the moment, but it is an unexpected finding and the clinical investigators want to look at it further,” he said in an interview.

An additional, important observation was that daily aspirin treatment led to a strong trend toward a reduced rate of heart failure hospitalizations compared with the warfarin arm. Results from a prior study that compared aspirin and warfarin in heart failure patients, the Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) Trial, had indicated that aspirin boosted the rate of heart failure hospitalizations for acute exacerbations, and at the least the new findings “show that aspirin certainly did not make hospitalization any worse,” and may possibly have even reduced the heart-failure hospitalization rate, Dr. Homma said.

“It is a very important finding. Aspirin use in heart failure was a concern, but we didn’t see that,” he said at the meeting, which was sponsored by the American Heart Association.

WARCEF enrolled patients at 176 centers in 11 countries between 2002 and January 2010, with more than a third of the patients enrolled in the United States. The study was funded by the National Institute of Neurological Disorders and Stroke.

The study also featured an unusual design, in that it was completely double-blinded even though half the patients received warfarin and half did not. To maintain the blind, all patients regularly went to warfarin clinics where their blood was drawn and INR reports generated that their physicians then used to adjust their warfarin dosages, even for the patients who received dummy warfarin pills.

“Neither patients nor their physicians knew who was on warfarin and who was on aspirin, so this gives us great confidence about the study results. It removes the possibility that one group received more intensive care,” Dr. Thompson said.

WARCEF was sponsored by the National Institute of Neurological Disorders and Stroke. Dr. Homma and Dr. Thompson said that they had no disclosures.

Subject Codes:
cardiology; neurology;

http://www.imng.com

February 03, 2012 04:58 PM EST

Dr. Shunichi Homma

Medicare Proposes TAVR Coverage Criteria

Fri, 03 Feb 2012 19:53 GMT

BY NASEEM S. MILLER
Elsevier Global Medical News
Breaking News

Medicare officials have released a coverage proposal for transcatheter aortic valve replacement 3 months after the procedure was approved in the United States.

The Centers for Medicare and Medicaid Services’ proposal restricts the procedure’s coverage where all of the following five criteria are met:

• The procedure meets Food and Drug Administration–approved criteria, and an FDA-approved device is used.

• Two cardiac surgeons evaluate the patient’s suitability for open valve replacement surgery.

• The procedure is performed in a facility that meets a certain level of experience. The document breaks down the criteria by centers with or without previous transcatheter aortic valve replacement (TAVR) clinical trial experience. All centers are required to participate in a prospective national TAVR study, and be committed to the Heart Team concept.

• The cardiac surgeon and interventionalist meet certain qualifications and levels of experience.

• The patient is enrolled in the prospective national registry for TAVR. The treating physician team also needs to be participating in the national registry.

The memo arrived ahead of its March 28 due date.

It also comes just days after four leading cardiovascular societies issued a document providing detailed guidance on TAVR implementation in centers across the United States.

Heart Teams, a national registry, and careful evaluation and selection of patients are also among the societies’ consensus document highlights.

In the United States, the first valve to be used for TAVR (the Edwards Lifesciences Sapien valve) was approved in November 2011. The valve is currently approved for use in inoperable patients with severe aortic stenosis. Other use of the Sapien valve is limited to clinical trials. Medtronic’s CoreValve is also in being studied in large U.S. trials.

CMS opened the national coverage determination analysis in September, before Sapien was even approved, in response to a request from the American College of Cardiology and the Society for Thoracic Surgeons to establish the criteria for national Medicare coverage of the minimally invasive valve procedure.

The CMS proposal is a step in the national coverage analysis process, in which the agency decides whether an item or service is covered by Medicare.

The CMS coverage proposal is open for comment until March 3. The agency is expected to make a final decision by May of this year.

Subject Codes:
cardiology; surgery;

http://www.imng.com

February 03, 2012 02:53 PM EST

Anemia Triples Post-Stroke Mortality Risk

Fri, 03 Feb 2012 15:04 GMT

BY ALICIA AULT
Elsevier Global Medical News
Breaking News

NEW ORLEANS (EGMN) – Patients with a very low or a very high hematocrit are at higher risk for death after a stroke, and anemic patients are at greatest risk, according to a study presented at the International Stroke Conference sponsored by the American Heart Association on Feb. 2.

Previous studies have shown that extremes of hematocrit increase mortality after myocardial infarction, congestive heart failure, and kidney disease. Dr. Jason J. Sico of the VA Connecticut Healthcare System and researchers from the Department of Veterans Affairs medical system explored whether there was a similar association in stroke. Previous stroke studies had not adjusted for stroke severity or a large number of comorbidities.

They found that “among stroke patients, severe anemia is a potent predictor of dying throughout the first year after a stroke,” said Dr. Sico, who is also an assistant professor of neurology at Yale University, New Haven, Conn.

The researchers abstracted medical records for a sample from 131 Veterans Health Administration (VHA) hospitals of 3,965 patients admitted for a confirmed diagnosis of ischemic stroke in fiscal 2007. Patients with unavailable hematocrits, those who received thrombolytics, or those whose charts had inconsistent death dates were also excluded.

The hematocrit, taken from 24 hours of admission, was divided into six tiers: less than or equal to 27% (defined as severe anemia); 28%-32% (moderate anemia); 33%-37% (mild anemia); 38%-42% (normal); 43%-47% (normal); and greater than or equal to 48% (polycythemia).

Researchers adjusted for age, National Institutes of Health Stroke Scale (NIHSS) score, comorbidities (including pneumonia, hypertension, hypercholesterolemia, diabetes, and history of cancer and heart disease), and Acute Physiology and Chronic Health Evaluation (APACHE)-III scores.

A total of 2% of the 3,750 patients analyzed had severe anemia, 6.2% had moderate anemia, and 17.9% had mild anemia. About 64% were in the normal categories. A total of 9% had a high hematocrit of greater than or equal to 48%.

People with lower hematocrits tended to be older and have higher APACHE scores, a higher Charlson index, a history of heart disease, and were more likely to have diabetes.

The risk of death was 2.5 to 3.5 times higher for patients with severe anemia (P = .013 for in-hospital and 30-day mortality; P = .002 at 6 months and P = .001 at 1 year). A high hematocrit was independently associated only with in-hospital mortality (OR 2.9, P = .004).

The study showed that having a history of severe anemia put stroke patients at a higher risk of death than having a history of other conditions, including cancer and heart disease, said Dr. Sico.

There are several potential mechanisms to explain why anemia might increase the risk of death, he said in an interview. With lower hematocrits, less blood and less oxygen circulate to various parts of the body. Long-term anemia also impairs the ability of the brain’s blood vessels to respond appropriately to a stroke.

A higher hematocrit also decreases blood flow to brain, said Dr. Sico. It causes a more turbulent blood flow to the brain, which could predispose the stroke patient to having a bad outcome.

Dr. Sico said that the study’s findings were limited to men because no women had been analyzed.

But he concluded that stroke patients with low or high hematocrits should be evaluated for potentially reversible causes, and that they should also be closely monitored during the post-stroke period.

Dr. Sico reported having no financial disclosures. The study was funded by the VA Health Services Research and Development Quality Enhancement Research Initiative.

Subject Codes:
top_stories; cardiology; neurology;

http://www.imng.com

February 03, 2012 10:04 AM EST

Intracranial Bleed Risk Higher in Warfarin Than Rivaroxaban Users

Fri, 03 Feb 2012 01:10 GMT

BY MICHELE G. SULLIVAN
Elsevier Global Medical News
Breaking News

NEW ORLEANS (EGMN)– Compared with warfarin, the new-generation anticoagulant rivaroxaban was associated with a 40% lower risk of intracranial hemorrhage in patients with atrial fibrillation who were taking the agents to prevent stroke.

Since its approval by the Food and Drug Administration last fall, rivaroxaban has been deemed an alternative to warfarin, especially among those patients who have trouble maintaining a stable international normalized ratio, who have warfarin side effects, or who find the constant warfarin monitoring untenable, Dr. Graeme Hankey said at an international stroke conference.

Rivaroxaban also doesn’t involve the medication and food interactions that can make warfarin problematic, said Dr. Hankey, head of the stroke unit at Royal Perth Hospital, Western Australia.

“Many patients don’t want to take warfarin for these reasons,” he said in an interview. “Rivaroxaban doesn’t have these interactions. It has a stable, predictable effect with once-a-day dosing and doesn’t require this constant monitoring.”

Dr. Hankey’s subanalysis of the pivotal ROCKET-AF study, which compared rivaroxaban with warfarin, also determined that some patients had up to a 4-fold increased risk of an intracranial bleed while taking either of the anticoagulants.

The initial study – Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation or ROCKET AF – included 14,264 patients with atrial fibrillation; a history of stroke, TIAs, or systemic embolism; and at least two of the following stroke risk factors: heart failure or a left ventricular ejection fraction of 35% or less; hypertension; an age of 75 years or more; or the presence of diabetes mellitus. Patients were randomized to receive dose-adjusted warfarin or rivaroxaban. Those with normal creatinine clearance received 20 mg daily of the study drug; those with a decreased clearance received 15 mg rivaroxaban daily.

The study’s main end point – a combination of stroke or systemic embolism – was similar in both groups (about 2% per year). The rates of myocardial infarction, and major bleeding also were not significantly different. Vascular mortality and all-cause mortality were nearly identical. However, there was a significant difference in intracranial hemorrhage, favoring rivaroxaban (0.8%; 55 vs. 1.2%; 84). (N. Engl. J. Med 2011;365:883-91). Fatal bleeding occurred in less than 1% of each group.

Dr. Hankey’s subanalysis examined the drug’s effect on intracranial hemorrhage, “probably the most-feared complication of anticoagulation,” according to the investigator. It also examined independent risk factors for intracranial hemorrhage regardless of which drug the study patients took.

He and his colleagues found 172 intracranial hemorrhages in ROCKET-AF – a rate of about 7% per year. Of these bleeds, 128 were intracerebral, 5 subarachnoid, 38 subdural, and 1 extradural. Patients taking rivaroxaban were 40% less likely to have an intracranial hemorrhage than were those taking warfarin.

The subanalysis identified factors that significantly increased the risk of an intracranial bleed. The largest by far were race and concomitant use of clopidogrel. Compared with whites, blacks were more than 400% more likely to have a brain bleed (odds ratio, 4.2), while Asians were 200% more likely. Those taking clopidogrel plus either warfarin or rivaroxaban were 250% more likely to have a bleed than were those not taking an additional anticoagulant (OR, 2.50).

Other significant associations with brain bleeds were as follows:

• High diastolic blood pressure – 21% increased risk for every 10 mm/Hg above normal.

• Poor kidney function – 10% increased risk for every 10 mL/min decrease in creatinine clearance.

• History of stroke or transient ischemic attack – 55% increased risk.

• Low platelets – 8% increased risk;

• Low albumin – 37% increased risk.

The FDA approved rivaroxaban in 2011, to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation.

Dr. José Biller, chairman of neurology at Loyola University, Maywood, Ill., said that although rivaroxaban is another tool in the armamentarium for patients at risk of stroke, he thinks it’s premature to make a paradigm shift away from warfarin.

“Clearly, ROCKET-AF showed us that rivaroxaban was noninferior to warfarin,” said Dr. Biller, the lead author on a recently published review of the new-generation anticoagulation drugs (Expert Rev. Neurother. 2012;12:179-90). “This subanalysis showed that rivaroxaban also had a decreased rate of intracranial hemorrhage, compared with warfarin, but we must keep in mind that the drug did not affect the ROCKET-AF trial’s primary end points of stroke or systemic embolism, nor did it decrease mortality, compared with warfarin.

“One of the biggest concerns about rivaroxaban and some of the other new antithrombotic agents is that we have no established protocol to deal with bleeding, should it occur, as we do with warfarin. At this point, we really don’t know the best way to deal with a bleed. This is something we will learn only with more time,” he said. And compared with the other new-generation anticoagulants apixaban and dabigatran, rivaroxaban seems to have a few more side effects, such as nausea and increased liver enzymes.

“Rivaroxaban and these other drugs do have benefit of being fixed-dose medications taken once or twice a day, and which don’t require the monitoring that warfarin does. But they are going to be more expensive.

“If a patient is under treatment with warfarin and is stable, and if the monitoring schedule is acceptable and there are no major INR fluctuations, I don’t think there is any indication to shift treatment. If the patient has difficulty maintaining a therapeutic INR or if the monitoring is inconvenient, then I suspect patients might welcome the use of one of these fixed-dose agents,” Dr. Biller said.

ROCKET-AF was supported by Johnson & Johnson Pharmaceutical Researchand Development and by Bayer HealthCare. Dr. Hankey was an investigator on the trial and has received honoraria for speaking on the study drug. He is also a consultant for Boehringer Ingelheim and Bayer, which make dabigatran and rivaroxaban, respectively.

Dr. Biller had no disclosures.

Subject Codes:
top_stories; new_drugs; general_primary; cardiology; neurology;

http://www.imng.com

February 02, 2012 08:10 PM EST

Longer Monitoring Needed to Detect Cause of Cryptogenic Stroke

Thu, 02 Feb 2012 22:06 GMT

BY ALICIA AULT
Elsevier Global Medical News
Breaking News

NEW ORLEANS (EGMN) – Continuous cardiac outpatient telemetry monitoring for at least 21 days may be necessary to accurately identify atrial fibrillation as the cause of cryptogenic stroke, according to the results of a single-center, retrospective study.

Identifying these patients is important because many could be treated with anticoagulants that would reduce their stroke risk, said Dr. Daniel J. Miller, a neurologist at Henry Ford Hospital, Detroit.

About a third of all strokes are of unknown etiology. Paroxysmal atrial fibrillation (AF) is a potential cause of cryptogenic stroke and transient ischemic attacks (TIAs), and carries a high risk of future strokes, Dr. Miller said during a press briefing at the International Stroke Conference.

Physicians have not been sure about the best way to monitor these patients or how long to monitor them.

He and his colleagues followed-up on two small studies: one conducted by Dr. Ashis H. Tayal and colleagues (Neurology 2008;71:1696-1701) and another by Dr. Archit Bhatt and associates (Stroke Res. Treat. 2011 [doi:10.4061/2011/172074]). The Tayal study showed a 23% AF detection rate in cryptogenic stroke patients monitored for longer than 21 days. The Bhatt study found a similar AF rate in cryptogenic stroke.

Dr. Miller and his coinvestigators reviewed the records of 156 Henry Ford Hospital patients who’d had a cryptogenic stroke or TIA and had undergone monitoring with the Cardionet Mobile Cardiac Outpatient Telemetry (MCOT) device, which is commonly used at Henry Ford

The patients had a mean age of 68 years and half were women. The vast majority (97%) were not taking an anticoagulant. Hypertension was common, present in 87% of the patients. They had a fairly low mean score of 3 on the National Institutes of Health Stroke Scale (NIHSS), indicating that the stroke had not been severe.

After monitoring, 27 (17.3%) of the 156 patients had paroxysmal AF. The AF events lasted less than 30 seconds in two-thirds of the patients and longer than 30 seconds in 26%. The remaining 8% had persistently occurring AF. This finding was not surprising and was consistent with the Tayal report, Dr. Miller said in an interview. The monitors are very sensitive, in particular for those events longer than 30 seconds, but they might miss some episodes of less than 30 seconds, he said.

The review showed that the rate of AF detection rose with increased duration of monitoring. The detection rate on a Kaplan-Meier curve was estimated to be 4% at 48 hours, 9% at 7 days, 14% at 14 days, and 20% by 21 days. “Our study does show that in order to capture all these events you should continue to monitor for at least 21 days,” Dr. Miller said.

A multivariate Cox regression analysis showed that for all patients, female gender (P = .002), premature atrial complexes (PAC) on electrocardiogram (P = .001), a 1-cm increase in the diameter of the left atrium (P = .033), and a 10% decline in left ventricular ejection fraction (P = .008) all were associated with increased risk of AF. For stroke patients, female gender, PAC, and increasing stroke severity on the NIHSS were all associated with increased risk.

PAC, a premature beat from the atrium, has been shown to be associated with AF. It was an especially strong predictor of AF in this study, Dr. Miller said.

He urged further study to determine optimal monitoring beyond 21 days for patients with cryptogenic stroke or TIA.

Subject Codes:
top_stories; cardiology; neurology;

http://www.imng.com

February 02, 2012 05:06 PM EST

New EVAR Devices for Abdominal Aortic Aneurysm Evolving

Thu, 02 Feb 2012 16:40 GMT

BY MITCHEL L. ZOLER
Elsevier Global Medical News

MIAMI BEACH (EGMN)–Devices for endovascular repair of abdominal aortic aneurysms are evolving, with new sizing or other innovations either recently on the market or in studies.

The new products expand the scope of patients who are candidates for endovascular aneurysm repair (EVAR), and in one case bring a new approach to EVAR into the clinic.

During a session at ISET 2012, an international symposium on endovascular therapy, seven experts gave the following quick updates on what’s new in EVAR for 2012:

•Making devices smaller. Downsizing constitutes a major trend for several new EVAR devices. The Endurant device helped blaze the lower-profile path, introducing a device delivered in an 18-Fr catheter for 23- to 25-mm diameter aortic stent grafts. Endurant received Food and Drug Administration marketing approval in 2010, and results from the U.S. pivotal trial for this device appeared last year (J. Vasc. Surg. 2011;54:601-8). In the pivotal trial, the major adverse event rate after 30 days was 4%; after 1 year, the patency rate was 97%, no patients had type I endoleaks, and the rate of secondary procedures was 5%, said Dr. Dittmar Böckler, professor and medical director of vascular surgery at the University of Heidelberg (Germany). An even smaller version of the same device, Endurant II, places a 28-mm bifurcated segment of an aortic stent graft into an 18-Fr delivery catheter – reduced from 20 Fr in the existing Endurant device – and has longer limbs to maximize coverage, changes that will further “expand options” for this device, he said.

Other EVAR devices take the downsizing trend even further. The Ovation Abdominal Stent Graft System, which received FDA marketing approval last November, has a 14-Fr outer diameter. For the time being, Ovation “is the lowest-profile commercially available device, expanding the population that is suitable for EVAR,” said Dr. Horst Sievert, director of the cardiovascular center at Sankt Katharinen Hospital in Frankfurt, Germany. The FDA also made Ovation the first EVAR to be approved as a humanitarian use device (defined as an instrument aimed at a U.S. patient population that grows by fewer than 4,000 new cases annually). Ovation is approved for use in patients with iliac or femoral artery access that is less than 7 mm in diameter, and for treating an aorta with an inner neck diameter of 15.5-17.4 mm. The clinical trial results for Ovation showed “excellent short-term results,” Dr. Sievert said. In the U.S. pivotal trial with 161 patients, the major adverse event rate after 1 month was 2.5%, he noted.

The Zenith Low Profile, a third low-profile EVAR device delivered in a 16-Fr sheath, is nearing marketing approval. The FDA already has data from a U.S. pivotal trial with 120 patients, and a decision on marketing approval should come sometime this year, said Dr. Roy K. Greenberg, a vascular surgeon at the Cleveland Clinic. Although he voiced enthusiasm for lower-profile devices that allow EVAR in patients who would not be able to accommodate larger devices, he also cautioned that “as we get lower-profile devices, we need to pay more attention to iliac disease. Postimplantation residual stenosis is critical for patients with [calcified] iliac disease.”

Another issue with new devices is establishing their long-term performance. “New devices aren’t necessarily better; they’re just different. I think there are some advantages to new devices, but we don’t have a track record with respect to their long-term behavior,” Dr. Greenberg said.

Finally, the INCRAFT low-profile EVAR device starts testing in a pivotal U.S. trial in February. INCRAFT matches Ovation with a 14-F outer-diameter delivery sheath, said Dr. Robert M. Bersin, medical director of endovascular services at Swedish Medical Center in Seattle. Its track record so far comes from the first 60 patients who received the device, at six centers in Germany and Italy, he added.

•High aortic neck angles. Aside from size, the aortic-neck angle provides another opportunity to broaden the EVAR device market. The Aorfix EVAR device is highly flexible and designed to deal with aortic neck angles of 60 degrees or greater. The stent has a “unique design, because a 60-degree angle is typically an exclusion for most [EVAR] devices,” said Dr. William A. Gray, director of endovascular services at Columbia University in New York.

He reviewed the roll-in phase data from the PYTHAGORAS trial, which enrolled 62 patients with aortic neck angles smaller than 60 degrees; two-thirds of these first-phase patients had necks angled at more than 45 degrees. In the roll-in phase, “the Aorflex device has given excellent results in patients with typical anatomy,” and the results serve “as a good prelude to the high-angle cases,” he said.

The main phase of the trial, which planned to enroll up to 150 patients with high-angle aortic necks, has also finished, but those data are not yet publicly available. Lombard Medical, the company developing this device, submitted the main-phase data to the FDA, and should make the results public in the next 6 months, he said.

•Prefenestrations.Perhaps one of the more exciting new devices is the Ventana fenestrated system, an “off-the-shelf” device that comes with prefenestrations for the renal arteries that precludes the need for a custom-made device.

A current “unmet clinical need” for EVAR is a device to address patients with a short or nonexistent infrarenal neck, something that occurs in about a quarter of abdominal aortic aneurysm patients, said Dr. Daniel Clair, professor and chairman of vascular surgery at the Cleveland Clinic.

The system can potentially treat even aneurysms that include the renal arteries. The material used in the device is a multilayer polytetrafluoroethylene that forms small branches at the fenestrations that reach out into the renal arteries, and the device is delivered in a 22-Fr sheath.

Pilot studies used this system successfully on 15 patients outside the United States last year, and in February the next phase starts with another 30-50 patients scheduled for treatment both in and outside the United States, he said.

The pivotal U.S. trial (with 122 patients scheduled for treatment) also starts this year, with Dr. Clair as the principal investigator.

•Aneurysm sealing. Also in development is an EVAR-like device that’s not a stent. The Nellix system seals an aneurysm endovascularly, by deploying bags that fill with a liquid polymer that quickly solidifies to seal an aneurysm sac around a pair of stents. The system delivers the polymer at greater than blood pressure to extrude all blood from the aneurysm sac, said Dr. Lindsay Machan, a vascular surgeon at the University of British Columbia in Vancouver. This facilitates treatment of aortas with short or severely angulated necks. “The polymer anchors the devise at the bifurcation,” Dr. Machan said, producing “remarkable” stability, better than devices that rely on barbs for anchoring.

So far, operators have used the Nellix system in 47 patients in New Zealand and Latvia, the first 31 with a first-generation device and, more recently, the remaining 16 patients with a second-generation version. More than 1 year of follow-up exists for 34 patients. These cases had 100% technical success with no ruptures, no conversions to open repair, and no endoleaks (either persistent or type II), he said. Two patients needed a secondary procedure, one for renal insufficiency, the other for a type I endoleak after 15 months.

The pivotal U.S. trial is planned to start later this year. “This ‘out-of-the-box’ technology addresses many shortcomings of EVAR, and uses a simple insertion procedure that takes 20-30 minutes,” Dr. Machan said.

Dr. Böckler said that he has financial relationships with W.L. Gore, Medtronic, VASCOPS, and Siemens. Dr. Sievert said that he has financial relationships with TriVascular, W.L. Gore, and 55 other device companies. Dr. Greenberg said that he has an ownership interest in Cook Medical. Dr. Bersin said that he has financial relationships with Cordis Endovascular, W.L. Gore, Cook, and Bard. Dr. Gray said that he is a consultant to Cordis. Dr. Clair said that he has financial relationships with Endologix, ev3, Medtronic, Boston Scientific, and Covidien. Dr. Machan said that he has financial relationships with Boston Scientific, Cook, Calgary Scientific, Endologix, and Ikomed.

Subject Codes:
cardiology; surgery;

http://www.imng.com

February 02, 2012 11:40 AM EST

Horst Sievert

Pregnancy Does Not Preclude Safe DVT Treatment

Wed, 01 Feb 2012 22:24 GMT

BY MITCHEL L. ZOLER
Elsevier Global Medical News
Breaking News

MIAMI BEACH (EGMN)–Women who develop a deep vein thrombosis while pregnant can safely undergo removal of the clot without jeopardizing their pregnancy, based on a recent experience with 11 cases at one U.S. center.

“Not many vascular surgeons are willing to perform thrombectomy in pregnant women, and most physicians fear thrombolytic therapy in pregnant patients,” Dr. Anthony J. Comerota said at ISET 2012, an international symposium on endovascular therapy.

But in reality, there is no evidence that thrombolysis poses any special risk during pregnancy, in part because the drugs that are usually used – urokinase, streptokinase, or tissue plasminogen activator (TPA) – do not cross the placenta, and therefore do not exert any fibrinolytic effect on a fetus, he said. In addition, the relatively recent introduction of pharmacomechanical methods for thrombolysis have “accelerated our enthusiasm and strengthened our confidence that this is an effective and safe strategy for treating extensive DVT [deep vein thrombosis] during pregnancy,” said Dr. Comerota, a vascular surgeon and director of the Jobst Vascular Institute in Toledo, Ohio.

“Pregnancy need not be a major contraindication for successful management of extensive DVT. We need to minimize radiation, monitor the fetus, and control uterine contractions, but we should treat healthy, pregnant women [who have] a DVT the same way we treat healthy nonpregnant women” who have a DVT, he said in an interview. “The extraordinary concern for risk to the pregnancy [from clot removal] seems substantially overstated.”

Because pregnancy produces a prothrombotic state, the risk that a healthy, pregnant woman has for DVT is about sixfold higher than her risk when not pregnant. Until now, most physicians deferred endovascular or surgical management of women who develop a DVT during pregnancy, and have relied exclusively on medical treatment with heparin or low-molecular-weight heparin, a strategy that is often ineffective. “What pushed me to treat women earlier during their pregnancy was that I saw patients who did not receive therapy until after delivery, and by then the clot became more organized – a mix of collagen and scar inside the vein – -and caused severe postthrombotic disability,” Dr. Comerota said.

Recently, he treated 11 pregnant women (10 with an iliofemoral thrombosis and 1 with the clot in her superior vena cava). One woman was in the first trimester, two were in the second, and eight were in the third trimester. Three patients underwent clot removal by open surgery, with the other eight treated by endovascular methods, including six who were treated with catheter-delivered TPA and one who received urokinase via catheter. Other endovascular tools that were used as needed included ultrasound clot treatment and rheolytic thrombectomy. In all cases, these treatments successfully removed the clot. One women developed hematuria and required a transfusion following her clot removal, and another patient developed a popliteal artery pseudoaneurysm. None of the patients had a recurrent DVT; two developed mild postthrombotic symptoms.

In one case, the fetus spontaneously aborted 5 days after the procedure secondary to antiphospholipid antibody syndrome, which had also triggered the thrombosis. The other 10 cases resulted in successful pregnancies and live deliveries, one surgically and the other nine vaginally. Three of the women had successful subsequent pregnancies, Dr. Comerota said.

Dr. Comerota said that he has been a speaker for and a consultant to Covidien, a company that makes some of the devices used in these procedures.

Subject Codes:
womens_health; cardiology; surgery;

http://www.imng.com

February 01, 2012 05:24 PM EST

Anthony J. Comerota

Most New ADHD Patients Don’t Need Cardiac Testing

Wed, 01 Feb 2012 21:16 GMT

BY MICHELE G. SULLIVAN
Elsevier Global Medical News
Breaking News

NEW YORK (EGMN) – An electroencephalogram probably isn’t necessary for most youngsters starting a medication for attention-deficit/hyperactivity disorder.

Some easy screening questions should be enough to identify any children who have cardiovascular risks that a stimulant could exacerbate, Dr. James J. McGough said at a psychopharmacology update sponsored by the American Academy of Child and Adolescent Psychiatry.

“I am going to suggest that we end this neurosis” about cardiovascular risks during ADHD treatment. “The questions to ask before starting a kid out on any psychotropic medication are the same you would ask any child who is getting a sports physical,” said Dr. McGough, chief of staff of the Resnick Neuropsychiatric Hospital at the University of California, Los Angeles.

The biggest fear is sudden cardiovascular death – an event usually associated with sport. “I don’t think a month goes by that I don’t hear about a soccer player, cheerleader, or basketball player who has had a sudden death. It’s tragic, but it happens. The bottom line is that there is a three times greater risk of sudden death associated with sports than with being on a stimulant.”

In light of this statistic, he said: “There would be more sense in doing an EKG on every high school athlete, but no one is calling for that.”

The key questions that should be in every ADHD assessment focus on family and personal history:

• Have you ever fainted while exercising?

• Is there a family history of sudden cardiac death?

�� Is there any cardiac abnormality or a heart murmur?

If the answer to any of these is “yes,” the patient should see a pediatric cardiologist before starting a stimulant medication. Otherwise, Dr. McGough said, “The benefit of an EKG is really not worth the cost.”

The American Heart Association raised concerns about cardiac death and ADHD medications in 2008, when it recommended that every child have an EKG read by a pediatric cardiologist before beginning stimulant medication. However, the group noted, although the test was preferred, it should not be mandatory (Circ. 2008;117:2407-23).

A 2009 postmortem case-control study seemed to bolster the recommendation (Am. J. Psychiatry 2009;166:992-1001).

The authors examined amphetamine exposure among 1,128 children aged 7-19 years, half of whom had a sudden unexplained death and half of whom died in motor vehicle accidents. Ten of those in the sudden death group had amphetamine exposure compared to two in the accident group – a significant difference. The authors concluded that amphetamines could increase the risk of sudden death.

Despite this study, the Food and Drug Administration decided not to require cardiac testing for every ADHD start, Dr. McGough said. More recent studies suggest that the risk is very small or absent.

“There are about a half dozen papers on this now,” including one published recently and two large retrospective cohort studies published last year.

The current study examined the risk of cardiovascular events in a database of 171,126 youngsters aged 6-21 years. There were three new cardiac symptoms and less than one cardiac event per 1 million days of current stimulant use. Compared to the reference group, the adjusted odds ratio of cardiac events during current use was 1.18, and with past use, 0.93 (J. Am. Acad. Child Adolesc. Psychiatry 2012;51:147-56).

Last November, the New England Journal of Medicine published a cohort study of 1.2 million children and young adults, 373,667 of whom were currently using ADHD medications. There were 81 serious cardiovascular events, a rate of 3 per 100,000 person-years (N. Engl. J. Med. 2011;365:1896-904).

Another study appeared in Pediatrics. The cohort consisted of 241,417 ADHD medication users. No significant associations were found with sudden death, ventricular arrhythmia, or all-cause mortality. None of the strokes identified during exposed time to ADHD agents were validated (Pediatrics 2011;127:1102-10).

“I think it’s time we put an end to this brouhaha,” Dr. McGough said.

Dr. McGough disclosed that he is on the advisory boards of NextWave Pharmaceuticals, Noven Pharmaceuticals, Shiongi, Shire Pharmaceuticals, and Supernus Pharmaceuticals. He also is a consultant for Alexa Pharmaceuticals and MedImmune.

Subject Codes:
sports; mental_health; pediatrics; cardiology;

http://www.imng.com

February 01, 2012 04:16 PM EST

Two Stents Show Peripheral Artery Efficacy

Wed, 01 Feb 2012 20:46 GMT

BY MITCHEL L. ZOLER
Elsevier Global Medical News
Breaking News

MIAMI BEACH (EGMN)–Two different self-expandable nitinol stents showed efficacy for treating peripheral arterial stenoses, according to results from two separate, pivotal trials. The Food and Drug Administration is reviewing data from both studies, with the agency’s decisions expected later this year, researchers said at ISET 2012, an international symposium on endovascular therapy.

The EverFlex stent underwent testing in femoropopliteal arteries in 287 patients with peripheral artery disease at 44 centers in the United States and Europe. The trial enrolled patients with Rutherford-Becker clinical categories of 2, 3, or 4, and at least a 50% stenosis. The average age of the patients enrolled was 68 years, two-thirds were men, 43% had diabetes, 88% had hypertension, 40% had Rutherford category 2 disease, and 56% had category 3 disease. The average lesion length was 9 cm, with 29% of patients having a lesion that was 20 cm long.

One of the study’s major goals was testing a single-stent strategy, and 95% of enrolled patients received a single stent, said Dr. Jon S. Matsumura, the trial’s principal investigator. Using single stents for long lesions may reduce the risk of stent fracture.

The primary efficacy end point of DURABILITY II (Safety and Effectiveness Study of EverFlex Stent to Treat Symptomatic Femoral-Popliteal Atherosclerosis) was primary patency in the treated vessel 1 year after stent placement. Study results from 226 patients with follow-up data showed primary patency in 77% after 1 year in an actuarial analysis. This level of success exceeded the 33% performance goal, set on the basis of literature controls using angioplasty interventions, said Dr. Matsumura, professor and chairman of the division of vascular surgery at the University of Wisconsin in Madison.

The study’s primary safety end point was the combined rate of major adverse effects after 30 days. The results showed no such events within that period, with no deaths, no amputations of treated limbs, and no instances of clinically driven target vessel revascularizations.

At 1 year after treatment, a single episode of stent fracture – a class V fracture in the stent’s transaxial spiral configuration – had occurred.

Also at 1 year, 84% of patients had at least a single-level improvement, compared with their baseline Rutherford clinical category, with 65% of patients improving by two or more categories. The researchers collected data on the baseline and 1-year follow-up treadmill walking tests in 29 patients, and 69% of these patients showed improvements in walking distance, with an average increase of about 420 feet per patient.

ORION (A Boston Scientific Trial of the Epic Nitinol Stent in the Treatment of Atherosclerotic Lesions in Iliac Arteries) enrolled 125 patients with a new or restenotic lesion in the common or external iliac artery, or in both, and with a Rutherford-Becker clinical category of 1, 2, 3, or 4. Lesions had to be no longer than 13 cm, with a reference vessel diameter of 5-11 mm. The study enrolled patients at 28 U.S. centers during May 2009–December 2010.

The study population had an average age of 61 years, two-thirds were men, a third of the patients had diabetes, and 76% had hypertension. The average lesion length was just over 3 cm, and the average vessel diameter was just under 8 mm. The operators in the study placed a total of 187 stents into 166 lesions in the enrolled patients.

This study’s primary end point was the combined rate of major adverse events after 9 months of follow-up. These events occurred in four of the 117 patients who were followed for 9 months, a 3.4% rate that consisted entirely of target vessel revascularizations; in three cases, these revascularizations occurred because of stent thrombosis episodes, said Dr. Daniel G. Clair, principal investigator for the study and chairman of vascular surgery at the Cleveland Clinic. The study patients had no other events that made up the major adverse event composite: no deaths within 30 days, no MIs during hospitalization, and no amputations of the index limb during 9 months of follow-up.

The 3.4% observed major adverse event rate ran significantly below the study’s prespecified performance goal of 17%. The 17% goal derived from an expected 8% rate based on the historical literature, plus an added margin of 9%. The actual rate “was much lower than predicted by the literature,” based on how iliac artery stents performed in prior studies, Dr. Clair said.

The percentage of patients with a Rutherford-Becker clinical category of 2-4 dropped from 93% at baseline to 18% at 9 months. Average ankle brachial index increased from an average of 0.79 at baseline to 0.97 at 9 months. The primary patency rate at 9 months was 96%.

The results “support the safety and efficacy of the stent in iliac arteries,” Dr. Clair concluded.

The DURABILITY II trial was sponsored by Covidien, the company developing the EverFlex stent. The ORION trial was sponsored by Boston Scientific, the company developing the Epic stent. Dr. Matsumura said that he has received research grants from Covidien and from Abbott, Cook, Endologix, and W.L. Gore. Dr. Clair said that he has been a consultant to Boston Scientific, and also to Covidien, Endologix, ev3, and Medtronic.

Subject Codes:
cardiology;

http://www.imng.com

February 01, 2012 03:46 PM EST

Daniel Clair

Updated Criteria Revisit PCI Appropriateness Scenarios

Wed, 01 Feb 2012 17:14 GMT

BY DIANA MAHONEY
Elsevier Global Medical News
Breaking News

Percutaneous coronary intervention is an appropriate procedure for patients with two-vessel coronary artery disease with proximal left anterior descending artery and for those who have three-vessel disease with a low coronary artery disease burden, but it may not be reasonable for patients with three-vessel disease and intermediate-to-high CAD burden.

That’s according to new appropriate use criteria for coronary revascularization released Jan. 30 by the American College of Cardiology Foundation and key specialty and subspecialty societies.

In the new document – the first focused update to the original Appropriate Use Criteria (AUC) for Coronary Revascularization published in 2009 – the latter scenario is graded as “uncertain,” as is percutaneous coronary intervention (PCI) for patients with isolated left main stenosis and those with left main stenosis and additional CAD with low CAD burden. Further, the procedure is inappropriate for patients with left main stenosis and additional CAD with intermediate to high CAD burden, Dr. Manesh Patel of Duke University, Durham, N.C., and colleagues on the Appropriate Use Criteria Task Force reported (J. Am. Coll. Cardiol. 2012 Jan. 30 [doi: 10.1016/j.jacc.2011.12.001]). In the previous appropriate use document, PCI was deemed inappropriate for low burden left main disease and uncertain for low-burden three-vessel disease, they stated. Coronary artery bypass grafting (CABG), on the other hand, maintained its 2009 rating of appropriate for all six clinical scenarios, the authors wrote.

In addition to the changes to the PCI appropriateness ratings above, the updated ratings indicate that coronary revascularization of the presumed culprit artery is appropriate for acute coronary syndrome patients with unstable angina/non–ST-segment elevation MI (UA/NSTEMI) with intermediate risk features – defined as a thrombolysis in myocardial infarction (TIMI) score of 3-4 – for short-term risk of death or nonfatal MI, while it is uncertain for UA/NSTEMI patients with low-risk features (TIMI score of 2 or less) for short-term risk of death or non-fatal MI. Among asymptomatic patients without prior bypass surgery, revascularization is inappropriate for those with one or two-vessel CAD with no proximal left anterior descending artery involvement and no history of invasive testing.

The updated criteria are intended to fill in the gaps identified in the prior criteria and to take into account results of clinical trials that have been reported since the initial publication, including the Synergy Between PCI With TAXUS and Cardiac Surgery (SYNTAX) trial comparing the two revascularization procedures in patients with left main or triple-vessel CAD, the authors wrote.

For the 2009 criteria, the writing group identified 180 clinical scenarios reflecting common patient presentations in everyday cardiology practice which were then rated by an expert panel comprising interventional and noninterventional cardiologists, surgeons, internal medicine physicians, and health outcomes researchers using a modified Delphi exercise to assess whether an invasive revascularization procedure would be appropriate, inappropriate, or uncertain based on symptom status, extent of medical therapy, risk level, and coronary anatomy (J. Am. Coll. Cardiol. 2009;53:530-53).

For the updated document, the writing group reassessed the clinical scenarios and identified those warranting reevaluation, expansion, or consolidation, the authors explained. In this regard, they identified and reexamined four indications possibly affected by the results of the SYNTAX trial, splitting two of them to represent levels of disease burden, as noted above. They also identified a gap in the clinical scenarios related to lower-risk UA/NSTEMI patients and asymptomatic patients with one- or two-vessel CAD not involving the proximal left anterior descending artery in whom no noninvasive testing had been performed, and developed indications to address the omissions.

Basing appropriate use criteria on current understanding of the technical capabilities and potential patient benefits, the technical panel scored each indication on a scale from 1-9. A given procedure was considered appropriate for an indication if the median score was 7-9; uncertain if the median scores was 4-6; and inappropriate if the median score was 1-3.

Clinicians can use the updated criteria as decision support or educational tools when considering the need for revascularization, the authors wrote. “Moreover, these criteria can be used to facilitate discussion with patients and/or referring physicians about revascularization,” they stated, noting also that “facilities and payers may choose to use these criteria either prospectively in the design of protocols or pre-authorization procedures, or retrospectively for quality reports.”

Importantly, the appropriate use criteria “are intended to evaluate overall patterns of care regarding revascularization rather than adjudicating specific cases,” the authors wrote. While the criteria reflect a general assessment of when revascularization may or may not be useful for specific patient populations, “physicians and other stakeholders should continue to acknowledge the pivotal role of clinical judgment in determining whether revascularization is indicated for an individual patient.”

Dr. Patel reported having no financial disclosures. Relationships with industry of all the writing committee members are included in the AUC document.

Subject Codes:
cardiology; surgery;

http://www.imng.com

February 01, 2012 12:14 PM EST

Manesh Patel

LVAD Support Optimal During Bridge to Transplant

Tue, 31 Jan 2012 21:00 GMT

BY MARK S. LESNEY
Elsevier Global Medical News
Breaking News

FT. LAUDERDALE, FLA. (EGMN) – Left ventricular assist devices were associated with a significant survival advantage compared with all other support pathways implemented before heart transplant in an analysis of more than 13,000 patients.

There are a variety of support pathways available to eventual heart transplant recipients, but there is little information concerning comparative outcomes of patients bridged with the various treatments. Such information could provide valuable insight for clinical decision making and organ allocation policy, according to Dr. Tara Karamlou.

A large database study was conducted using the United Network Organ Sharing Dataset to track outcomes of status 1 heart transplant recipients from 2000 to 2010. Dr. Karamlou of Seattle Children’s Hospital, and her colleagues, grouped transplant recipients based on the use of support pathways prior to transplant, including patients transitioning from one support pathway to another.

Dr. Karamlou reported her group’s results using Kaplan-Meir plots to compare time-related mortality among the different support-pathway groups. The study sought to uncover multivariable factors for time-related death using hazard regression models, she said at the annual meeting of the Society of Thoracic Surgeons.

There were six initial support pathways used in the 13,250 status 1 heart transplant patients identified in the database. These comprised inotropes (7,607); left ventricular assist devices (LVAD, 4,034); intra-aortic balloon pump (IABP, 729); biventricular assist devices (BIVAD, 521); extracorporeal circulation membrane oxygenation (ECMO, 316); and right ventricular assist devices (RVAD, 43).

“Multivariable analysis showed that LVAD use conferred a significant survival advantage compared with all other support pathways [hazard ratio, 0.71; P greater than .001],” said Dr. Karamlou. All other support treatments showed significantly increased risk of posttransplant death compared with LVAD treatment, including inotropes (HR, 1.1); RVAD (HR, 1.9); and ECMO (HR, 2.2).

There were 2,175 patients in the analysis who transitioned (either escalation or reduction) from one support pathway to another: no support to LVAD; LVAD to BIVAD; inotropes to LVAD; LVAD to inotropes; BIVAD to LVAD; and ECMO to LVAD. Among these patients, those who began with ECMO or BIVAD support followed by LVAD had improved posttransplant survival comparable to that of patients who began on LVAD and continued it throughout their course of pretransplant support.

LVAD support, especially in the setting of bridge to transplant, has clearly undergone several modifications that have made it safer and easier to implant and maintain, she added. Implantation of an LVAD in the current era, based on these findings, has survival superior to all other mechanical circulatory support pathways, and is equivalent to inotropic therapy. Additionally, in patients who are able to be weaned from biventricular support (ECMO and BIVAD therapy), LVAD implantation allows recovery of posttransplant survival to levels equivalent to primary LVAD–only therapy. This finding gives surgeons and cardiologists critical prognostic information regarding triage to pretransplant support pathways.

“Several key issues remain unresolved and, based on our results, will require further investigation. For example, the timing and clinical status of the patient surrounding both initial support and transition (either escalation or de-escalation) could not be determined from our data. In my mind, this is a crucial issue because delayed institution of mechanical support can have serious repercussions and, given the significantly increased risk of death with ECMO and BIVAD, a delay in de-escalation of therapy to LVAD could also confer an important survival disadvantage,” she said.

“Organ allocation policy development and clinical decision making might benefit by considering these results in order to maximize the societal benefits of heart transplants,” Dr. Karamlou concluded.

Dr. Karamlou reported having no financial disclosures.

Subject Codes:
cardiology; surgery;

http://www.imng.com

January 31, 2012 04:00 PM EST

Dr. Tara Karamlou

TAVR Gets a Detailed Road Map

Tue, 31 Jan 2012 19:23 GMT

BY NASEEM S. MILLER
Elsevier Global Medical News
Breaking News

To ensure appropriate implementation and use of transcatheter aortic valve replacement in medical centers across the United States, four leading cardiovascular organizations have pooled their knowledge and issued a consensus document.

The document comes 2 months after the Food and Drug Administration approved the first minimally invasive transcatheter aortic valve replacement (TAVR) system (J. Am. Coll. Cardiol. 2012 Jan. 31; doi:10.1016/j.jacc.2012.001).

The document reviews in detail several aspects of the procedure, including the current state of evidence, patient selection, management of complications and steps to integrating TAVR into practice.

“Our goal in crafting this expert consensus document is to provide a clear road map for the use of TAVR as it reaches patients across the United States,” Dr. Michael J. Mack, medical director of cardiovascular surgery at Baylor Health Care System, Heart Hospital Baylor Plano (Tex.), president of the Society of Thoracic Surgeons, and vice chair of the writing committee, said in a statement.

The report also recommends establishment of a national registry by cardiovascular organizations and not the industry, to create standard definitions and data specifications and to avoid the potential for conflict of interest.

In the expert consensus, the organizations also stress that the procedure’s rollout is a “key issue” in the United States. “The rollout is influenced by the societal beliefs in a free market, convenient and timely access to medical care, patient and physician expectations, as well as return on investment by companies and institutions alike,” according to the report.

What complicates the rollout, they added, is the proliferation of advanced cardiovascular facilities.

Take, for instance, Los Angeles County, which has 33 cardiovascular surgical and primary ST-elevation myocardial infarction centers. If all these centers were to offer TAVR, the result would be “the dilution of concentrated experience,” the report stated.

So, establishment of specialized centers of excellence should be a top priority, the report advised.

“As this technology is introduced into practice, detailed and agreed upon protocols are needed to ensure we achieve optimal clinical results,” Dr. David R. Holmes, professor of medicine at Mayo Clinic in Rochester, Minn., president of the American College of Cardiology, and chair of the writing committee, said in a statement.

Nearly 45,000 patients have received TAVR around the world, but the experience with the procedure in the United States lags far behind that in Europe. Five different valves are currently in widespread use across Europe. In the United States, the first valve, Edwards Sapien, was approved in 2011 for use in inoperable patients with severe aortic stenosis. Other use of the Sapien valve is limited to clinical trials. Medtronic’s CoreValve is also in being studied in large U.S. trials. The report lists several next-generation devices under investigation.

“TAVR innovation is a major advance in treating aortic stenosis and sick, elderly patients should have access to this new treatment so they can resume normal, active lives,” Dr. Mack said in a statement. “These guidelines are a coordinated effort from the cardiovascular community to help ensure the appropriate use of TAVR therapy for optimum patient safety.”

The American College of Cardiology Foundation, the American Association for Thoracic Surgery, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons were the main authors of the consensus document. Eight other medical and consumer groups were involved in the writing and endorsement of the document.

Dr. Mack and Dr. Holmes reported no relevant disclosures.

Subject Codes:
top_stories; cardiology; surgery;

http://www.imng.com

January 31, 2012 02:23 PM EST

The hybrid elements of transcatheter aortic valve replacement should feel the benefit of this consensus document on proper TAVR procedure.

Whistleblower Alleges Fraudulent Stent Use

Tue, 31 Jan 2012 15:38 GMT

BY ALICIA AULT
Elsevier Global Medical News
Breaking News

In another example of the continuing scrutiny being given to cardiac procedures, a cardiologist has filed a whistleblower suit against former colleagues, alleging that they knowingly bilked federal health programs over a 4-year period, from 2001-2005.

The suit was filed by Dr. Tullio Emanuele in the U.S. District Court for the Western District of Pennsylvania. It was under seal until Oct. 2011, and was served on the defendants on Jan. 17. The defendants have 20 days to respond.

Dr. Emanuele is now based in Kentucky, but had worked in an Erie-based practice, Medicor Associates. In his suit, he claims that his former colleagues at Medicor and at Flagship Cardiac, Vascular, and Thoracic Surgery of Erie – along with the UPMC Hamot Medical Center of Erie – engaged in billing practices that defrauded Medicare, Medicaid, and Tricare, among other insurers.

Carly Manino, manager of media relations at UPMC Hamot, said that the hospital would not comment. “It’s our policy not to comment on pending litigation,” she said.

Whistleblower or “qui tam” suits are filed under the False Claims Act. Such suits allow private citizens with knowledge of false claims against the government to bring a lawsuit on behalf of the United States and to share in any recovery, according to the U.S. Department of Justice.

So far, the federal government has declined to intervene in the case, but the suit can be advanced by private litigators, according to Andy Stone, cocounsel on the Emanuele suit. The government may intervene at a later point, said Mr. Stone, whose practice is in Pittsburgh. The government can seek triple the amount of damages determined by the courts. Mr. Stone said that it’s not clear how much might be at stake in the case before discovery, but that given the potential number of claims, it could be millions of dollars.

The Pennsylvania suit also accuses the cardiologists and the hospital of violating the antikickback statutes that prohibit improper patient referrals.

In addition, the suit alleges that the named physicians performed unnecessary medical procedures, including cardiac catheterizations and vascular surgeries.

Mr. Stone said that he believes that cases alleging overuse of stents or other percutaneous interventions may be brought more often.

“These are important cases because the dollar amounts are big. The incentives are there – and substantial patient risk. You put those two things together and that makes for a real serious abuse situation,” he said.

Indeed, the Emanuele suit seems to be the latest in a high-profile battle over the appropriateness of cardiac procedures, particularly stent placement. Last spring, Greensburg, Pa.–based Excela Health said that it had found that stents had been unnecessarily placed in almost 200 patients. In a turnaround, that health system has just won accreditation under the Accreditation for Cardiovascular Excellence (ACE) program that is sponsored by the Society for Cardiovascular Angiography and Interventions and the American College of Cardiology Foundation.

Those two organizations, along with the Maryland Chapter of the ACC, have been working to head off regulation of stent procedures, according to an editorial in the Journal of the American College of Cardiology. Instead, they are hoping to convince the state to require all Maryland hospitals to submit to a mandatory accrediting process through the groups’ ACE program.

The state of Maryland began looking into stenting as the result of another qui tam suit filed by three cardiologists against St. Joseph Medical Center in Towson, Md. The hospital settled for $22 million. The suit alleged that St. Joseph paid kickbacks in return for referrals from MidAtlantic Cardiovascular Associates.

St. Joseph also settled charges that cardiologist Mark Midei performed unnecessary stent procedures.

Subject Codes:
cardiology;

http://www.imng.com

January 31, 2012 10:38 AM EST

Metformin May Lower Pancreatic Cancer Risk in Women

Tue, 31 Jan 2012 13:00 GMT

BY SHARON WORCESTER
Elsevier Global Medical News
Breaking News

Metformin use was associated with a decreased risk of pancreatic cancer in women, but not in men, in a large case-control study involving more than 19,300 U.K. primary care patients.

Additionally, use of insulin and sulfonylureas was found in the study to be associated with increased risk of pancreatic cancer in both men and women, Dr. Michael Bodmer of the University of Basel, Switzerland, and his colleagues reported online in the Jan. 31 issue of the American Journal of Gastroenterology.

Overall, metformin use was not found to be associated with pancreatic cancer in 2,763 patients with a first-time diagnosis of pancreatic cancer, compared with 16,578 matched controls with no such diagnosis – all from the U.K.-based General Practice Research Database, which includes data on more than 8 million individuals (adjusted odds ratios, 1.01, 0.92, and 0.87 for those who received 1-9, 10-29, and 30 or more metformin prescriptions, respectively), the investigators said.

The findings were similar when analysis was restricted to cases with pancreatic surgery, radio/chemotherapy, or with a specific oncology code, and also when analysis was restricted to diabetic patients. However, in an analysis by gender, long-term metformin use was associated with a decreased risk of pancreatic cancer in women (adjusted OR, 0.43), but not in men (adjusted OR, 1.59), they found (Am. J. Gastroenterol. 2012 Jan. 31 [doi10.1038/ajg.2011.483]).

As for long-term use of sulfonylureas and insulin, the overall analysis demonstrated a “materially increased risk of pancreatic cancer (adjusted OR, 1.90 and 2.29, respectively), and as with metformin, the findings were closely similar in those with pancreatic surgery, radio/chemotherapy, or an oncology code, while in the analysis restricted to patients with diabetes, the adjusted odds ratios for long-term use of sulfonylureas and insulin were 1.59 and 1.69, respectively.

In contrast with the findings regarding metformin, the increased risk of pancreatic cancer among long-term users of sulfonylureas was mainly restricted to women (adjusted OR, 3.05), the investigators said.

Cases in this study were individuals with a first-time diagnosis of pancreatic cancer before the age of 90 years between 1995 and 2009. Controls had no diagnosis of pancreatic cancer and were matched based on calendar time, age, sex, general practice, and number of years of active history in the database before the index date. The average age was 70 years, and 46% were men.

The analyses were conducted using the index date shifted back in time by 2 years to account for cancer latency, the investigators explained.

Using that same shifted index date, the investigators also looked for a link between diabetes history and the risk of pancreatic cancer, and found one. “Overall, the adjusted odds ratio of pancreatic cancer associated with a recorded diagnosis of diabetes mellitus was 1.22. When we stratified the risk of pancreatic cancer by diabetes duration, the odds ratio decreased with increasing duration of diabetes; the odds ratios for a diabetes history of less than 2, 2-5, 5-10, or greater than 10 years were 1.71, 1.21, 0.94, and 0.71, respectively,” they said.

In the analysis using the recorded index date, rather than the shifted date, the overall odds ratio for pancreatic cancer in diabetic patients compared with nondiabetic patients was 1.60, and for those with disease duration of less than 2 years, 2-5 years, 5-10 years, and greater than 10 years were 3.30, 1.13, 0.72, and 0.56, respectively.

The finding of an effect modification by gender for the use of metformin was “somewhat unexpected and could not be explained by confounding by use of estrogens,” the investigators said, noting that the finding should be interpreted with caution since it is based on a limited number of exposed cases and controls, and since there is no obvious pathophysiologic explanation.

Also, the findings regarding metformin differed somewhat from those of prior smaller studies showing an overall decrease in pancreatic cancer with long-term metformin use.

The findings regarding sulfonylureas and insulin, however, support those of prior studies, and as with metformin, effect modification by gender seemed to have a role: The increased risk with long-term use of sulfonylureas was mainly seen in women, and the increased risk with insulin was mainly seen in men.

“Of importance, in our study, neither short-term use of metformin or sulfonylureas, nor insulin was associated with altered relative risk estimates for pancreatic cancer, indicating that our study design effectively eliminated detection bias and/or bias by intensification of antidiabetic therapy due to undiagnosed pancreatic cancer,” they said.

Also the finding of a link between diabetes mellitus and increased risk for pancreatic cancer, which was restricted to those with newly diagnosed diabetes, strongly supports the hypothesis suggested by other authors that short-term diabetes mellitus is likely caused by pancreatic cancer.

“Although uncontrolled confounding by dietary habits or physical activity may be of importance, these findings do not support a causative role for diabetes mellitus for development of pancreatic cancer,” they noted.

This study was partially funded by the Swiss Cancer League and the Research Fund of the University of Basel, Switzerland. None of the authors had relevant disclosures.

Subject Codes:
top_stories; gastroenterology; diabetes; general_primary; endocrinology; womens_health; cardiology;

http://www.imng.com

January 31, 2012 08:00 AM EST

Neurologic Improvements Possible in Neonatal ASO

Tue, 31 Jan 2012 02:05 GMT

BY MARK S. LESNEY
Elsevier Global Medical News
Breaking News

FT. LAUDERDALE, FLA.(EGMN) –The use of full-flow cardiopulmonary bypass, coupled with neurological monitoring, improved cognitive and motor outcomes in a prospective neurologic outcome study of 97 neonates with transposition of the great arteries (both single- and two-ventricle lesions) who underwent an arterial switch operation.

The cohort study, conducted by Dr. Dean B. Andropoulos and his colleagues at the Texas Children’s Hospital in Houston, examined early MRI changes and longer-term neurodevelopmental outcomes after the arterial switch operation (ASO) was performed using a cardiopulmonary bypass (CPB) protocol that avoided deep hypothermic circulatory arrest (DHCA) and low-flow CPB.

The ASO was performed by using CPB with 150-mL/kg per min flows with no low-flow CPB or DHCA; pH stat management; hematocrit 30% or higher; and hypothermia to 24° -28° C. Regional oxygen saturation greater than 50% was maintained by using near infrared spectroscopic monitoring.

Neurologic assessment was performed using brain MRI performed immediately before the operation and 7 days postoperatively. The Bayley Scales of Infant and Toddler Development, Third Edition were used at 12 and 36 months (mean score of 100).

Dextrotransposition of the great arteries was present in 31 of the 97 enrolled patients. Ten of these 31 (32%) had preoperative MRI change, and 19 of 31 (61%) showed new postoperative MRI change, with 75% showing minimal new white matter injury, he said at the annual meeting of the Society of Thoracic Surgeons.

At 2 months, Bayley Scales were performed on 17 of the patients. Their mean cognitive score was 106.5, mean motor score was 90.4, and mean language score was 89.4. Twelve patients had Bayley III testing at 36 months, with a cognitive score of 106.5, motor score of 107.4, and language score of 98.2.

“Our series demonstrates a significant incidence of pre-existing MRI changes, and 61% have new postoperative changes, but all changes in this series were mild,” said Dr. Andropoulos.

“At 12 months, the cognitive score of these children was above the population mean, but their motor and language performance was lower. By 36 months, language and motor scores had improved significantly. Thus, full-flow CPB coupled to cerebral monitoring may improve neurological outcomes.”

Because of these results, “future studies of ASO patients should include short- and long-term neurodevelopmental studies,” he said.

With greatly improved 30-day neonatal arterial switch operation mortality rates (for example, at the Texas Children’s Hospital in Houston there were no 30-day hospital mortalities for 175 ASOs since 2000), there are increasing expectations for better neurologic outcomes, according to Dr. Andropoulos, and such considerations are increasingly important.

Dr. Andropoulos reported having no financial conflicts.

Subject Codes:
cardiology; surgery;

http://www.imng.com

January 30, 2012 09:05 PM EST

Dean B. Andropoulos

Perspective - A Promising Therapy for a Vexing Problem

Mon, 30 Jan 2012 20:42 GMT

BY JOHN M. FLACK, M.D., M.P.H.
Elsevier Global Medical News

Renal sympathetic denervation is a promising new therapy that – at least over the short term – has proved to be an effective, device-based approach to the treatment of severe resistant hypertension.

Resistant hypertension is a significant, vexing problem for the clinical community. However, the true number of individuals with resistant hypertension in the United States is probably higher than the recent NHANES (National Health and Nutrition Examination Survey) data reporting that more than 9 million (28%) of the roughly 33 million uncontrolled hypertensives had apparent treatment-resistant hypertension, defined as having a blood pressure greater than 140/90 mm Hg despite taking at least three antihypertensive medications of different classes (Circulation 2011;124:1046-58).

Our contemporary experience in referral hypertension clinics suggests that this estimate may be a tip of the iceberg, as some patients treated with one to two distinct antihypertensive drug classes will ultimately meet diagnostic criteria for apparent treatment-resistant hypertension after intensification of their antihypertensive drug therapy.

Resistant hypertension is important for several reasons.

First, despite the availability of more than 100 Food and Drug Administration–approved antihypertensive drugs, only one-half of all hypertensives have attained control of blood pressure to below target levels. Inadequate BP control leaves these patients at an avoidably high risk for pressure-related complications such as stroke, heart failure, retinopathy, and possibly chronic kidney disease and end-stage renal disease.

Second, the more antihypertensive drugs a patient is prescribed, the greater the likelihood of therapeutic noncompliance; the diagnosis of resistant hypertension requires prescription of at least three antihypertensive drugs. Polypharmacy in resistant hypertension increases the risk of drug-specific and/or dose-related side effects, and adds to the complexity of the antihypertensive regimen, all of which increase the likelihood of therapeutic noncompliance.

Finally, although lifestyle modifications such as dietary sodium restriction, weight loss, aerobic activity, and moderation of alcohol intake, alone or in combination, effectively lower BP, these interventions are mostly adjunctive therapy to pharmacologic therapies during hypertension treatment.

Thus, there is a compelling unmet need for therapeutic advances leading to the availability of novel, effective, safe, well tolerated, and well accepted antihypertensive therapeutic strategies.

Renal sympathetic denervation is a very promising therapy that merits more rigorous evaluation over the long term to more precisely estimate the durability of its blood pressure–lowering efficacy and safety. The current intervention strategy with Medtronic’s Symplicity catheter system is a one-time radiofrequency ablation of renal sympathetic nerves. Very importantly, the reduction in renal sympathetic nerve traffic of about 50%, although significant, is only partial.

Several aspects of this intervention, as currently performed, are attractive. The intervention depends on the cannulation and insertion of the specialized catheter into the renal arteries. In contemporary clinical practice, renal artery catheterization is performed routinely by a range of operators.

In addition, the intervention, as far as is known today, needs to be performed only once. Also, there is no internal hardware left inside the patient. Importantly, the observed BP lowering does not appear to be dependent on any specific type of antihypertensive drug therapy. Finally, this therapy does not depend on long-term adherence to daily drug therapy, which arguably increases its value to patients unwilling to adhere to medication consistently over the long term.

SYMPLICITY HTN-3 is a pivotal randomized, placebo-controlled trial for the Symplicity catheter system that will enroll over 530 patients with resistant hypertension and a systolic BP greater than 160 mm Hg despite full doses of three different antihypertensive drugs, one of which must be a diuretic. The BP-lowering efficacy will be more precisely quantified because approximately one-third of randomized participants will be in a sham intervention (placebo) group and – for the first time, longitudinal blood pressure changes will be assessed in a blinded fashion. Also, it is a 2:1 study, meaning two thirds of those randomized will receive renal artery radiofrequency ablation, providing a relatively large sample of treated individuals to be closely observed for an extended period of time.

The emergence of device-based strategies for the control of severe resistant hypertension represents a potentially landmark advance in hypertension therapeutics. Although device-based therapies are unlikely to fully supplant pharmacologic approaches, they do appear to work well with existing drug therapies to lower blood pressure, and may even lower oral medication requirements needed to control blood pressure.

These are exciting times in the field of hypertension therapeutics.

This column, “Heart of the Matter,” regularly appears in Cardiology News, an Elsevier publication. Dr. Flack is professor of medicine and physiology, chairman of the department of internal medicine at Wayne State University, Detroit, and a member of the Cardiology News Editorial Advisory Board. He consults for Medtronic as a member of the SYMPLICITY HTN-3 trial steering committee, and has received grants and research support from and/or has been a consultant for other companies including Merck, Novartis, Pfizer, GlaxoSmithKline, AstraZeneca, Mannheim, Bristol-Myers Squibb, and Backbeat Medical.

Subject Codes:
cardiology;

http://www.imng.com

January 30, 2012 03:42 PM EST

Poorer Outcomes Associated With Earlier VSD Repair

Mon, 30 Jan 2012 19:57 GMT

BY MARK S. LESNEY
Elsevier Global Medical News
Breaking News

FT. LAUDERDALE, FLA (EGMN) – Early repair – within one week – of acquired ventral septal defect in patients with myocardial infarction was associated with a significantly higher mortality rate than was later repair in a retrospective review.

Acquired ventral septal defect (VSD), a relatively rare but devastating complication of myocardial infarction, frequently leads to cardiogenic shock and death. Surgical repair is generally required, although there is a high mortality.

To identify risk factors for poor patient outcomes, a study of the Society for Thoracic Surgeons National Database was performed to characterize patients undergoing post-MI VSD surgical repair, Dr. George J. Arnaoutakis said at the annual meeting of the Society of Thoracic Surgeons.

This retrospective review identified all adults (patients greater than 18 years of age) who underwent post-MI VSD repair between 1999 and 2010. The primary outcome measure was operative mortality and patients with congenital VSD were excluded.

“This largest to date study examining post-MI VSD repair was done in part to provide a surgical benchmark for future comparisons as percutaneous closure devices emerge to treat this condition,” noted Dr. Arnaoutakis of the division of cardiac surgery at Johns Hopkins University, Baltimore.

The demographics of the 2,876 patients included in the study were a mean age of 68 years; 56.5% of the patients were men; and 7.5% of patients had prior coronary artery bypass grafting (CABG) surgery. Operative characteristics included preoperative support with an intraaortic balloon pump (65%); urgent status (35%); emergent status (49.7%); and concomitant CABG (63.9%).

Timing of surgery was found to be an important predictor of risk, with 54% mortality occurring in patients who had repair less than 7 days after MI, and 18% mortality in those patients who had their surgery greater than 7 days after MI. Multivariate analysis also showed that the timing of MI with relation to VSD repair was independently associated with operative mortality.

Overall, major morbidity and mortality was high, at nearly 77%. Other surgical characteristics significantly associated with higher mortality included longer cardiopulmonary bypass time, preoperative dialysis, emergent surgery, and shock.

“Ventricular septal rupture remains a devastating complication after myocardial infarction,” he said, with a shorter time interval between MI and surgical repair of the VSD, being highly associated with operative mortality, Dr Arnaoutakis summarized.

He did point out that one flaw in this study based on the STS Database was that it could not account for patients who died while waiting for VSD repair, which might influence the results. In addition the overall incidence of acquired VSD was too low to determine the effect of individual surgeon or center volume on mortality rates.

Dr. Arnaoutakis agreed with audience suggestions that given the high overall mortality rate of surgical VSD closure, perhaps consideration of the new percutaneous closure devices and the possibility of ventricular assist device support might be reasonable options.

Dr. Arnaoutakis reported having no financial conflicts. Another researcher on the project reported research support from HeartWare International Inc. and Thoratec Corp.

Subject Codes:
cardiology;

http://www.imng.com

January 30, 2012 02:57 PM EST

Dr. George J. Arnaoutakis

Blood Pressure Differences Between Arms Flags Vascular Disease

Mon, 30 Jan 2012 17:43 GMT

BY MARY ANN MOON
Elsevier Global Medical News
Breaking News

A difference of 15 mm Hg or more in systolic blood pressure between a patient’s arms may signal the presence of asymptomatic peripheral vascular disease, according to a meta-analysis published online Jan. 30 in the Lancet.

Patients with this finding on physical examination might benefit from further assessment for peripheral vascular disease, much as those found to have reduced ankle-brachial pressure do. But simultaneous measurement of systolic BP in both arms is more easily done in the primary care setting, since such measurement in one arm is already routine and doesn’t require the time, experience, and training necessary for ankle-brachial pressure assessment, said Dr. Christopher E. Clark of the institute of health services research, University of Exeter (England), and his associates.

The most recent National Institute for Health and Clinical Excellence (NICE) guideline for hypertension states that a difference of 20 mm Hg or more between the arms is “unusual” and is often associated with underlying vascular disease, but doesn’t address smaller differences. The guideline also has advised routinely checking BP in both arms for several years, but most primary care physicians in the United Kingdom do not follow that advice, Dr. Clark and his colleagues said.

To establish whether small differences (10-15 mm Hg) in systolic blood pressure between the arms is associated with peripheral or cardiovascular disease, they performed a meta-analysis of 20 studies addressing the issue.

The investigators found that a difference of 10-15 mm Hg occurred in 12%-15% of the study subjects and was associated with peripheral vascular disease, with a low sensitivity but a very high specificity. This overall prevalence corresponds to published estimates in community studies, implying that findings of the meta-analysis are generalizable, they noted.

In particular, five studies that correlated systolic BP with findings on invasive angiography showed that a difference of 10 mm Hg or more was strongly associated with subclavian stenosis on the side with the lowest pressure (Lancet 2012 Jan. 30 [doi:10.1016/S0140-6736(11)61710-8]).

In pooled findings from studies with noninvasive assessments of vascular disease, a difference of 15 mm Hg or more was associated with not only peripheral vascular disease (sensitivity of 15% and specificity of 96%), but also with cerebrovascular disease (sensitivity of 8% and specificity of 93%) as well as increased cardiovascular and all-cause mortality.

In five studies, a difference as low as 10 mm Hg was associated with peripheral vascular disease (sensitivity of 32% and specificity of 91%).

These findings remained consistent across studies that used different methods of measuring BP, regardless of whether the cohorts comprised high-risk hospital-recruited patients or average-risk people living in the community.

Because this study was a misanalysis rather than a randomized clinical trial, “what constitutes a clinically important difference in systolic BP between arms is [still] unclear. However, we have associated a difference with an increased likelihood of peripheral vascular disease and with prospective differences in survival. Further research is needed to establish the upper limit of normal between-arm differences,” Dr. Clark and his associates wrote.

In an editorial accompanying this report, Dr. Richard J. McManus and Dr. Jonathan Mant wrote: “The high specificity (96%) of the association between a difference in systolic BP between arms of more than 15 mm Hg and peripheral vascular disease justifies the use of this measure as a sign of disease” (Lancet 2012 Jan. 30 [doi:10.1016/S0140-6736(11)61926-0]).

Ascertaining such differences should become part of routine care, “as opposed to a guideline recommendation that is mostly ignored,” said Dr. McManus of the department of primary care health sciences at the University of Oxford (England) and Dr. Mant of the department of public health and primary care at the University of Cambridge (England).

However, “the low sensitivity (15%) shows that measurement of differences is of little value as a screening test for peripheral vascular disease, and ankle-brachial pressure indices will still be necessary for diagnosis,” they noted.

Neither Dr. McManus nor Dr. Mant reported having any relevant financial disclosures.

This study was funded by the Royal College of General Practitioners, the South West GP Trust, and the Peninsula Collaboration for Leadership in Applied Health Research and Care. The investigators reported that they had no relevant financial disclosures.

Subject Codes:
top_stories; general_primary; cardiology;

http://www.imng.com

January 30, 2012 12:43 PM EST

A meta-analysis showed that systolic blood pressure difference between a patient’s arm could mean there is asymptomatic peripheral vascular disease.

Lifestyle Changes Cut Heart and Cancer Risks

Mon, 30 Jan 2012 15:16 GMT

BY BRUCE JANCIN
Elsevier Global Medical News
Breaking News

Meeting a greater number of the American Heart Association’s seven ideal cardiovascular health components is a twofer: not only is it associated with a reduced incidence of cardiovascular disease, but with a lower incidence of several major types of cancer as well.

By the same token, a separate study, this one in the cancer literature, has recently documented that individuals who adhere more faithfully to the American Cancer Society’s recommended lifestyle behaviors have sharply reduced mortality from cardiovascular disease as well as a lower risk of death due to cancer during long-term followup.

The two groups’ health promotion recommendations share many similarities. Both emphasize the importance of normal body weight, physical activity, and a healthy diet.

The new data documenting crossover benefits from the health promotion guidelines put forth by two major organizations focused on separate diseases are expected to bring renewed energy to collaborative AHA/ACS public health efforts.

“These findings can be used to simplify public health messages by emphasizing a core set of risk factors for prevention of multiple chronic diseases,” said Christina M. Shay, Ph.D., of the University of Oklahoma in Oklahoma City.

Such a stripped-down core message ought to help quell public frustration with often-conflicting health advice and contradictory medical recommendations, she added.

In 2004 the AHA, ACS, and American Diabetes Association formed the Preventive Health Partnership, an ongoing joint effort to reduce the burden of cardiovascular disease, stroke, cancer, and diabetes. The partnership has led to public health campaigns, public service announcements, and advocacy efforts.

Dr. Shay and coworkers recently examined the anticancer impact of adherence to the AHA’s seven ideal cardiovascular health components using the Atherosclerosis In Communities (ARIC) study cohort. ARIC is a prospective, multicenter, population-based study involving roughly 16,000 middle-aged white and African American men and women who have been reexamined at 3-year intervals. ARIC is rare among cardiovascular studies in that it has prospectively collected reliable data on cancer incidence.

The AHA’s seven ideal cardiovascular health components are a body mass index less than 25 kg/m², nonsmoking for at least the last 12 months, an untreated total cholesterol below 200 mg/dL, untreated blood pressure below 120/80 mm Hg, untreated fasting blood glucose of less than 100 mg/dL, at least 150 minutes per week of moderate or 75 minutes of vigorous physical activity, and a healthy diet score.

The healthy diet score requires meeting four out of the following five criteria: consumption of at least 4.5 cups of fruits and vegetables daily, eating two or more servings of fish per week, sodium intake of less than 1,500 mg per day, not more than 36 ounces of sugar-sweetened beverages per week, and at least three servings of whole grains daily.

This ARIC analysis involved 13,253 subjects with a mean baseline age of 54.1 years. The incidence of four major cancers – breast, prostate, lung, and colon – was monitored for 1978-2006. The risk of incident cancer dropped in stepwise fashion as a greater number of the ideal cardiovascular health components were met, such that individuals with five to seven of the components had an adjusted risk that was 38% less than that of individuals with none of the ideal health components (see graphic).

The inverse relationship between the number of ideal cardiovascular health components met and cancer risk was strongest for lung cancer. It was also significant for prostate and colon cancer, but not breast cancer.

Dr. Donald M. Lloyd-Jones calls the new findings “incredibly important.”

“What I think is really exciting and striking is the whole concept of trying to get everybody to just take one step forward. But that first step looks to be really key. Going from zero to one cardiovascular health component brings the biggest drop in risk, and that’s true both for cardiovascular disease and cancer. Maybe it’s because in just doing that one thing you actually pull a lot of other components from poor up to intermediate in a way that can’t be detected by this type of analysis,” observed Dr. Lloyd-Jones, chair of the department of preventive medicine at Northwestern University, Chicago.

The seven ideal cardiovascular health components were developed in conjunction with an AHA campaign to improve the cardiovascular health of Americans by 20% by the year 2020.

In another recent ARIC analysis, a separate group of investigators showed the 20-year incidence of cardiovascular disease was only one-tenth as high in subjects with six of the ideal cardiovascular health components as it was in those with none. As was the case in the cancer study by Dr. Shay and colleagues, the incidence of cardiovascular disease also decreased in stepwise fashion with an increasing number of cardiovascular health components being met (J. Am. Coll. Cardiol. 2011;57:1690-6).

Meanwhile, investigators at the American Cancer Society recently showed that a high level of adherence to cancer prevention recommendations regarding obesity, diet, physical activity, and alcohol consumption was associated with a 48% reduction in cardiovascular mortality in men and a 58% reduction in women. A high degree of adherence was also associated with a 30% reduction in cancer mortality in men and a 24% decrease in women (Cancer Epidemiol. Biomarkers Prev. 2011;20:1089-97).

The study involved 14 years of follow-up of 111,966 nonsmoking participants in the Cancer Prevention Study-II Nutrition Cohort.

Dr. Shay noted that because the relationship with alcohol intake appears to be different for cancer and cardiovascular disease, what to recommend regarding alcohol consumption will be an important topic of discussion in drawing up any new joint AHA/ACS health promotion message.

Comments for this article by Dr. Shay and Dr. Lloyd-Jones were made at the annual scientific sessions of the American Heart Association in Atlanta. Dr. Shay and Dr. Lloyd-Jones declared having no financial conflicts.

Subject Codes:
diabetes; general_primary; oncology; endocrinology; cardiology;

http://www.imng.com

January 30, 2012 10:16 AM EST

Adhering to the American Heart Association’s healthy diet score, which includes at least 4.5 cups of fruits and vegetables daily, can lower the risk of both cardiovascular disease and cancer.

CORRECTION: PCI Trial Halted After FFR’s Benefit Shown

Fri, 27 Jan 2012 21:24 GMT

Elsevier Global Medical News

A story titled “PCI Trial Halted After FFR’s Benefit Shown,” published January 24, 2012, misstated the primary end point for the ISCHEMIA trial. The primary end point will be time to cardiovascular death or nonfatal MI.

Subject Codes:
cardiology;

http://www.imng.com

January 27, 2012 04:24 PM EST

Carotid Endarterectomy More Cost-Effective Than Stenting

Fri, 27 Jan 2012 19:03 GMT

BY SHERRY BOSCHERT
Elsevier Global Medical News
Breaking News

SCOTTSDALE, ARIZ. (EGMN) – The cost of materials makes carotid artery stenting 40% more expensive than carotid endarterectomy with no relative clinical advantage, a retrospective study of 306 cases found.

Coronary artery stenting is not cost-effective in the routine management of carotid disease, Dr. Gregory D. Crenshaw and his associates reported at the annual meeting of the Southern Association for Vascular Surgery. The study won an award as the best study presented at the meeting.

The investigators compared 30-day clinical outcomes and hospital costs for 174 patients who underwent carotid endarterectomy (CEA) and 132 who underwent carotid artery stenting (CAS) with embolic protection at a single tertiary-care institution during January 2008–September 2010. Nine other patients who underwent CAS during that time were excluded because they had additional procedures that could bias the economic analysis.

Hospital costs in 2010 dollars averaged $9,426 for CAS, 40% higher than the mean $6,734 cost of CEA, said Dr. Crenshaw, a vascular and endovascular surgery fellow at the Ochsner Clinic Foundation, New Orleans.

Supply costs drove most of the difference, with supplies for CAS procedures averaging $3,667 more than for CEA. In 2010 terms, a carotid stent in the study cost $2,100-$2,495 and an embolic protection device cost $1,594-$1,695, compared with a cost of $90-$100 for a synthetic carotid patch used with endarterectomy.

Rates of adverse events did not differ significantly between groups. Stroke, MI, or death occurred in 2.3% of patients undergoing CEA and 3.8% of patients undergoing CAS.

Analyses of subgroups found the same trends in all subgroups – higher cost but no clinical advantage with carotid artery stenting, compared with carotid endarterectomy.

The investigators assessed hospital costs (not charges) by creating relative value units (RVUs) for expenses in the categories of labor, supplies, facility or equipment, and miscellaneous. The RVUs in the study were not related to Medicare work RVU valuations. The analysis did not include professional fees. Total expenses were normalized to 2010 costs based on the medical consumer price index.

The findings support previous studies suggesting similar clinical results from the two treatments but higher costs with carotid artery stenting.

The 2,502-patient Carotid Revascularization Endarterectomy Versus Stenting (CREST) trial found rates of 6.8% for CEA and 7.2% for CAS for a composite end point of periprocedural stroke, MI, death, or an ipsilateral stroke within 4 years (N. Engl. J. Med. 2010;363:11-23). In six studies between 1998 and 2010, the cost of carotid artery stenting exceeded that of carotid endarterectomy by 5%-118%, Dr. Crenshaw said.

When there is “clinical equipoise” between two therapies, costs become increasingly important, especially in the current era of rising health care costs and the need for efficient use of health care dollars, he said.

In Dr. Crenshaw’s study, the CEA group had a higher proportion of symptomatic patients (44%) and urgent cases (13%), compared with the CAS group (34% and 10%, respectively), but these differences did not achieve statistical significance. Compared with the endarterectomy group, the stenting group had significantly higher prevalences of coronary artery disease (61% vs. 37%) and congestive heart failure (18% vs. 5%).

Hospital costs were significantly higher with carotid artery stenting than with carotid endarterectomy for symptomatic or asymptomatic patients and for elective surgeries. Higher hospital costs for urgent cases treated by stenting compared with endarterectomy did not reach statistical significance.

Higher costs for symptomatic patients compared with asymptomatic patients in each subgroup were due to longer stays in the hospital and possibly due in part to extra costs for diagnostic imaging, he said. Overall, length of hospitalization was similar between the endarterectomy and stenting groups, a mean of 2 days in each.

Although the study was limited by not including professional fees in the analysis, including professional fees likely would not have changed the conclusions, he said. Medicare reimbursement for carotid artery stenting and for carotid endarterectomy is identical (averaging $1,167 in 2011). The average Medicare reimbursement for anesthesia for carotid endarterectomy is $350-$425, which also would not have changed the results significantly.

Dr. Crenshaw said he has no relevant conflicts of interest.

Subject Codes:
cardiology; surgery;

http://www.imng.com

January 27, 2012 02:03 PM EST

Gregory D. Crenshaw

Experts Can’t Pin Down Best Carotid Atherosclerosis Treatments

Fri, 27 Jan 2012 15:41 GMT

BY KERRI WACHTER
Elsevier Global Medical News
Breaking News

There are still no clear answers about the best treatments to use to prevent stroke in patients with carotid artery stenosis, even with the input of a Medicare advisory panel of experts.

The Medicare Evidence Development and Coverage Advisory Committee (MEDCAC) voted yesterday that they are only moderately confident that there is adequate evidence to determine which interventions – carotid artery endarterectomy (CEA), carotid artery stenting (CAS), or best medical treatment (BMT) – to use for different patient populations within the overall Medicare population. There’s unlikely to be any consensus in the near future as patient populations, detection, and treatments evolve.

“If there was ever a moving target problem in assessing health care interventions, this was one. The epidemiology is changing, the patient population is changing accordingly, [and] all of the interventions continue to change. We’ve not been keeping up in our data collection for the safety and effectiveness of these interventions as they continue to evolve,” commented committee chair, Clifford Goodman, Ph.D. “This means that to the extent that CMS is going to revisit its coverage decision making over time, this is an ongoing data collection issue. You’re not done collecting these data; you may not ever be done collecting these data as long as the patient population continues to change and as long as we have very innovative people improving these interventions.”

The panel was asked to vote on several questions regarding their confidence level that there is adequate evidence to identify specific patient populations and in some cases to select the best treatment option. Most scenarios garnered an “intermediate” confidence level. Confidence ran high only for the lowest-risk patients.

The panel voted that they had moderate confidence that the evidence is adequate to determine whether:

• Patients who are asymptomatic for carotid atherosclerosis can be identified as being at high risk for stroke in either cerebral hemisphere.

• Patients who are considering carotid revascularization can be identified as being at high risk for adverse events from CEA.

• Either CAS or CEA is the favored treatment strategy compared to BMT alone in patients with symptomatic carotid atherosclerosis and narrowing (at least 50% by angiography or at least 70% by ultrasound) who are not generally at high risk for adverse events from CEA.

• CAS, CEA, or BMT is the favored treatment strategy to decrease stroke or death for patients with asymptomatic carotid atherosclerosis.

In addition, for patients with symptomatic carotid atherosclerosis, who are not generally at high risk for adverse events from CEA, the panel had intermediate confidence that CEA is the favored treatment strategy to decrease stroke and death. For patients with asymptomatic carotid atherosclerosis, the panel had intermediate to high confidence that BMT is the favored treatment strategy to decrease stroke and death.

However, the panel was less confident that for patients with asymptomatic carotid atherosclerosis but with carotid narrowing – who are not generally considered at high risk for adverse events from CEA – that there is adequate evidence to determine whether or not either CAS or CEA is the favored strategy compared to BMT alone to decrease stroke or death in the Medicare population. The panel had very low confidence that there is adequate evidence to determine whether carotid artery screening of asymptomatic people decreases stroke or death.

The panel primarily based its decisions on the results of a handful of randomized, controlled trials with different patient populations, at different time periods, using different criteria to assess efficacy and safety. The results of the most recent of these – the CREST trial (Carotid Revascularization Endarterectomy vs. Stenting Trial) – were announced in 2010. The overall safety and efficacy of the CAS and CEA at 4 years were considered equivocal in terms of benefits for both men and for women, for patients who had previously had a stroke, and for those who had not (N. Engl. J. Med. 2010;363:11-23).

However, differences were seen between the two procedures for heart attacks and strokes. More heart attacks occurred with CEA – 2.3% vs. 1.1% – than for CAS, while more strokes occurred in the stenting group – 4.1% vs. 2.3% –than for CEA in the weeks following the procedure. There was also a difference in outcomes based on patient age. At approximately age 69 and younger, stenting results were slightly better, with CAS benefits increasing for decreasing patient age. Conversely, for patients older than 70, CEA results were slightly superior to stenting, with larger benefits for surgery with older patient age.

Instead of answering the question of which technique has better outcomes and safety, the trial left proponents of each technique still arguing.

In addition, BMT has not been assessed in clinical trials for many years and has evolved substantially since that time with the development and growing use of statins, antiplatelet medications, beta-blockers, ACE inhibitors, calcium channel blockers, and others.

What is lacking is a randomized, controlled trial pitting all three treatments against one another in a head-to-head comparison of the most current techniques, the panel noted repeatedly.

“I think that drawing conclusions from indirect comparisons of things that were done in the past is incredibly hazardous and we need to have a contemporary direct comparison to know what the right thing to do is,” argued panel member Dr. Larry B. Goldstein, who is a professor of neurology and director of the Duke Stroke Center in Chapel Hill, N.C.

Both surgery and CAS received a class I recommendation in guidelines published by the American Heart Association and other organizations in 2011 (J. Am. Coll. Cardiol. 2011;57:1002-44), but the level of evidence was stronger for CEA (level A) than for CAS (level B).

Planning is in the works for a possible CREST II trial in asymptomatic patients intended to compare intervention (with either CEA or CAS) vs. medical treatment alone. Many panel members expressed the need for this trial to proceed.

Twelve members of the panel reported that they did not have any relevant financial relationships. Dr. Spence reported receiving speaking fees from several pharmaceutical companies, Dr. Curtis reported that he owns stock in Medtronic and receives grant support from Boston Scientific, industry representative Dr. Peter Juhn works for Medco Health Solutions, and committee chair Dr. Clifford Goodman is the senior vice president at the Lewin Group, which has ties to both government and industry.

Subject Codes:
cardiology;

http://www.imng.com

January 27, 2012 10:41 AM EST

Feds Bar Generic Drug Maker Ranbaxy

Thu, 26 Jan 2012 18:48 GMT

BY BRENDA SANDBURG
“The Pink Sheet”
Breaking News

Generic drug manufacturer Ranbaxy Laboratories Ltd. will have to withdraw all drug applications that contain data generated at one of its facilities in India and relinquish 180-day marketing exclusivity for three pending abbreviated New Drug Applications under a consent decree for permanent injunction filed Jan. 25 by the U.S. Department of Justice.

The decree follows a lengthy investigation by the DOJ and the U.S. Food and Drug Administration that found numerous problems at three Ranbaxy facilities in India and one facility in Gloversville, N.Y.

According to the DOJ, the problems with Ranbaxy’s drug manufacturing and testing include failure to keep records showing that drugs had been manufactured properly; failure to investigate evidence indicating that drugs did not meet their specifications; failure to adequately separate the manufacture of penicillin drugs from nonpenicillin drugs in order to prevent cross-contamination; lack of adequate procedures to prevent contamination of sterile drugs; and inadequate testing of drug to ensure that they maintained strength and effectiveness until their expiration date.

The government also said that Ranbaxy submitted false data in drug applications, including backdating tests and submitting test data for which no test samples existed.

The consent decree is unprecedented in its scope, according to DOJ officials.

“This action against Ranbaxy is groundbreaking in its international reach – it requires the company to make fundamental changes to its plants in both the United States and India,” Assistant Attorney General Tony West said in a statement. “Submitting false data to the FDA in drug applications will not be tolerated.”

Ranbaxy said in a statement that the consent decree would not affect the company’s recently launched generic atorvastatin, because it is not manufactured in the facilities cited in the decree.

“Today’s announcement is the next step in the process of finalizing our agreement with the FDA to resolve this legacy issue,” according to Arun Sawhney, managing director of Ranbaxy Laboratories. “We are pleased with the progress we have made in upgrading and enhancing the quality of our business and manufacturing processes and remain committed to ensuring that all of our facilities and products meet the high standards that patients, prescribers and the public have come to expect from Ranbaxy.”

Ranbaxy announced earlier that it had entered into the consent decree with the FDA and had set aside $500 million to settle the related DOJ investigation. The consent decree itself does not mention the size of the settlement, although it does note that “if defendants fail to comply with any provision of the law or this decree at any covered facility and/or with respect to any affected application, then [they] ... shall pay to the United States of America $15,000 in liquidated damages for each day such violation continues.”

The company also agreed to relinquish the 180-day marketing exclusivity that it might have for three pending generic applications, but did not specify which drugs would be affected. The company also agreed to relinquish any 180-day marketing exclusivity that it may have for several additional generic applications if it fails to meet certain decree requirements by specified dates.

The manufacturing plants cited in the consent decree are the Paonta Sahib, Batamandi, and Dewas facilities, all in India, and the now-closed facility of Ranbaxy’s Ohm Laboratories subsidiary in Gloversville, N.Y. Import alerts for more than 30 products manufactured at the Paonta Sahib and Dewas sites have been in place since September 2008.

The consent decree also prevents Ranbaxy from manufacturing drugs for introduction to the U.S. market and for the President’s Emergency Plan for AIDS Relief Program at the four facilities.

Brenda Sandburg is a reporter for “The Pink Sheet.” This news organization and “The Pink Sheet” are owned by Elsevier.

Subject Codes:
top_stories; dermatology; cardiology;

http://www.imng.com

January 26, 2012 01:48 PM EST

New Oral Anticoagulants Troublesome in the Trauma Setting

Thu, 26 Jan 2012 14:40 GMT

BY PATRICE WENDLING
Elsevier Global Medical News
Breaking News

LAKE BUENA VISTA, FLA. (EGMN) – Patients on one of the powerful new oral anticoagulants are left without a good antidote for bleeding if they experience a traumatic injury.

The use of these agents is climbing as baby boomers age and the number of patients with atrial fibrillation continues its steady rise from 2.0 million in 1995 to a projected 4.34 million by 2030.

“If you think it’s an epidemic now, it will become even more so in the coming years,” Dr. Mark Cipolle, medical director of trauma and neurocritical care at Christiana Care Health System in Wilmington, Del., said at the annual meeting of the Eastern Association for the Surgery of Trauma.

Currently, no specific antidote is available for dabigatran (Pradaxa) or the factor Xa inhibitor rivaroxaban (Xarelto), both of which are approved for stroke prevention in nonvalvular atrial fibrillation and for deep vein thrombosis following hip or knee replacement surgery.

The oral Xa inhibitor apixaban (Eliquis) is under priority review for stroke and DVT prevention in atrial fibrillation and will likely move, sans antidote, into the marketplace later this year based on robust results from the recent ARISTOTLE trial.

Vitamin K and protamine sulfate are not expected to affect the anticoagulant activity of the new oral anticoagulants. Some centers have had anectodal success in reversing dabigatran with activated prothrombin complex concentrates (aPCCs), but this has not been widely adopted, according to Dr. Cipolle.

“Some of my colleagues in pharmacy think this may be the drug to help us reverse dabigatran ... but our blood bank hematologists aren’t thrilled about going to this because of the development of antibodies for the new agents,” he said.

The two aPCCs available in the United States are factor eight inhibitor binding activity (FEIBA) and anti-inhibitor coagulant complex, heat treated (Autoplex T); both are indicated for bypass therapy in patients with acquired inhibitors and contain the coagulation factors II, VII, IX, and X.

One of the first randomized trials to look at a specific PCC (Cofact) showed that a single bolus immediately and completely reversed the anticoagulation effect of rivaroxaban in 12 healthy volunteers who were taking 20 mg twice daily, but the PCC had no influence on the effect of dabigatran 150 mg twice daily (Circulation 2011;124:1573-9), said copanelist John Gallagher, clinical nurse specialist for the surgical/trauma ICU at the Hospital of the University of Pennsylvania in Philadelphia.

Recombinant activated factor VIIa has been widely studied in trauma, but not for this specific indication. Early research on antibody monoclonal development is showing promise, Dr. Cipolle said. A recent study described a monoclonal mouse antibody with a high and specific affinity to inhibit dabigatran in both human plasma and whole blood and in a rat in vivo model (J. Am. Coll. Cardiol. 2011;57:E1130).

The package insert for dabigatran recommends emergency dialysis as a reversal strategy, stating that about 60% of dabigatran is removed over 2-3 hours. “This [strategy] may work,” said Dr. Cipolle, observing that about 80% of dabigatran is renally excreted, compared with 66% of rivaroxaban and only 25% of apixaban.

Although not trivial, the half-lives of dabigatran (14-17 hours), rivaroxaban (9 hours), and apixaban (9-14 hours) are shorter than that of warfarin (40 hours), which means that “if you can wait and just not give them the drug, you are probably going to be okay,” he said.

Dr. Cipolle cautioned, however, that reversal of labs may not indicate loss of anticoagulant effects. Also, clotting factors and continued prolongation of anticoagulation assays do not indicate lack of effect.

“The drug industry has spent years developing a drug that we could take orally that you don’t have to measure, and all we want to do is measure it,” he said. “We would like to know just how much anticoagulant effect is present, and if our reversal strategies are working.

“A normal PTT [partial thromboplastin time] is very helpful, but other than that, the classic anticoagulation studies aren’t terribly helpful.”

This point was also referenced in a recent letter to the New England Journal of Medicine penned by two trauma surgeons and an emergency physician who treated several injured patients on dabigatran, all of whom had poor outcomes (N. Engl. J. Med. 2011;365:2039-40). Although their values for activated clotting time on rapid thromboelastography (rTEG) were grossly abnormal at the time of admission, all of the patients had normal results on conventional anticoagulation studies.

“Unfortunately, even with the aid of rTEG, supportive care is all that is available in the emergency setting,” wrote the authors, who strongly urged that hemorrhagic complications and death resulting from trauma be included as part of routine surveillance of all newly approved oral anticoagulants. The authors also argued that “the ability to perform rapid dialysis in patients with bleeding whose condition is unstable or in those with large intracranial hemorrhages will present an incredible challenge, even at level 1 trauma centers.”

Both Dr. Cipolle and Mr. Gallagher emphasized that institutions should have a protocol in place for anticoagulant reversal. The protocol should be based on evidence and practice guidelines, be transparent and modifiable, and identify specific anticoagulant agents, triggers for reversal such as intracranial hemorrhage or solid organ injury, and reversal strategies and methods for monitoring both the use of anticoagulants and reversal strategies, Mr. Gallagher said.

During a discussion of the study, attendees asked how to address anticoagulation at discharge in, for example, a 72-year-old man with early Alzheimer’s disease and a fourth admission for a fall. Dr. Cipolle replied that a recommendation would be placed in his chart based on his initial risk and that a hospitalist or cardiologist would also be called in. He observed that trauma surgeons typically overestimate the fall risk, compared with the stroke risk, and often feel that making such a recommendation may be out of their purview.

Audience member Dr. Ronald Gross, chief of trauma and emergency surgery at Baystate Medical Center in Springfield, Mass., said trauma surgeons need to play a more active role in anticoagulation. He added that physicians at his center have a conversation prior to discharge with every single fall patient about the risks and benefits of anticoagulation, and also contact their prescribing physicians.

Session moderator Dr. Lewis Kaplan, a trauma and critical care surgeon at Yale University, New Haven, Conn., said the nurse practitioners at his center call primary care physicians when trauma patients are admitted and make a follow-up call upon discharge. The trauma surgeon makes an anticoagulation recommendation at discharge, although half the time, despite the conversation, patients are back on their anticoagulants in a matter of weeks, Dr. Kaplan said.

Dr. Cipolle and Mr. Gallagher reported no conflicts of interest. Dr. Lewis serves as a consultant to Pfizer.

Subject Codes:
cardiology; surgery; emergency_trauma; gerontology;

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January 26, 2012 09:40 AM EST

Dr. Lewis Kaplan

Risk Factor Burden Characterizes Lifetime Cardiovascular Risks

Wed, 25 Jan 2012 22:00 GMT

BY SHARON WORCESTER
Elsevier Global Medical News
Breaking News

Adults with an optimal cardiovascular risk profile at age 55 have a substantially lower risk of death from cardiovascular disease through age 80 years, and a lower lifetime risk of fatal coronary heart disease, nonfatal myocardial infarction, and stroke, compared with those who have two or more major risk factors, according to a meta-analysis of 18 studies involving more than 257,000 adults.

The findings, which have important disease prevention and public health implications, were consistent across race and diverse birth cohorts, Dr. Jarett D. Berry of the University of Texas Southwestern Medical Center, Dallas and his colleagues report in the Jan. 26 issue of The New England Journal of Medicine.

The investigators conducted their meta-analysis at the individual level using data from studies that included black men and women and white men and women who were assessed for cardiovascular risk factors at ages 45, 55, 65, and 75 years. Patients were stratified into five mutually exclusive risk categories based on blood pressure, cholesterol level, smoking status, and diabetes status; only about 5% of participants comprised the optimal risk category, and about two-thirds comprised the two highest-risk groups.

The risk of cardiovascular disease-related death through age 80 years was 4.7% and 6.4% in men and women, respectively, who were nonsmokers without diabetes, and who had a total cholesterol level of less than 80 mg/dL, and blood pressure less than 120 mm Hg systolic and 80 mm Hg diastolic at age 55 years. The risk was 30% and 21% in men and women, respectively, with two or more major risk factors at that age, they said (N. Engl. J. Med. 2012;366:321-9).

The risk of fatal coronary heart disease or nonfatal MI was 3.6% and less than 1% in men and women, respectively, with the optimal risk factor profile, compared with 37.5% and 18.3% in men and women, respectively, with two or more major risk factors. The risk of fatal or nonfatal stroke was 2.3% and 5.3% in men and women with the optimal profile, compared with 8.3% and 10.7% in those with at least two major risk factors.

Similar patterns were seen based on assessments at other ages.

Significant, but expected, differences in the burden of risk factors were seen between older and younger birth cohorts, such as a higher prevalence of diabetes, a lower prevalence of smoking, and lower mean total cholesterol and systolic blood pressure in 55-year-old men born after 1920, compared with those born before 1920. Also, the burden of risk factors was higher among blacks than among whites, when participants were stratified according to race.

This approach to characterizing the lifetime risk of cardiovascular disease provides a more comprehensive assessment of overall disease burden in the general population than does the more common approach that calculates global, 10-year risk estimates, the investigators said, explaining that the majority of adults in the U.S. who are considered to be at low risk in the short-term, are actually at high risk across their lifespan.

It is an approach applauded by Dr. Paul D. Thompson, director of cardiology at Hartford Hospital, who said in an interview that many in the field have been troubled by the tendency to use 10-year risk estimates.

“Nobody wants to live just 10 years,” he said, adding that it’s important to be able to provide younger patients with a broader picture of lifetime risk.

“This study does not give us the ability to calculate 20- and 30-year risk, but it does introduce that concept,” he said.

It also introduces the intriguing and somewhat novel concept of primordial prevention, he said.

According to the investigators, the findings “strongly reinforce the influence of traditional risk factors on the lifetime risk of cardiovascular disease” and despite the development of notable secular trends in the prevalence of risk factors over the past 4 decades, the effect of those risk factors remained remarkably consistent across birth cohorts, they said.

In fact, they concluded that it is the presence or absence of traditional risk factors, rather than race or birth cohort, that appears to be the most consistent determinant of long-term cardiovascular disease risk – a conclusion based in part on a finding that despite an overall higher prevalence of risk factors in black than in whites, the lifetime risks of end points related to cardiovascular disease were similar in blacks and whites when risk factor profiles were similar.

This is not a surprising finding, Dr. Thompson said, noting that the study emphasizes “the classic risk factor model we’ve talked about all along,” and debunks some myths about age, race, and other factors.

“I think that’s a useful message,” he said.

The findings, according to the investigators, have important implications for clinical disease prevention and public health practice.

“First, the effect of untreated risk factors has been fairly constant for decades. Therefore, the present estimates of lifetime risk, made on the basis of current or projected risk-factor levels, may be important in estimating the future burden of cardiovascular disease in the general population. Second, efforts to lower the burden of cardiovascular disease will require prevention of the development of risk factors (primordial prevention) rather than the sole reliance on the treatment of existing risk factors (primary prevention),” they wrote.

Also, the findings are consistent with prior observations that the decline in cardiovascular event rates in the general population reflect changes in risk factor prevalence as opposed to treatment effects alone.

“For example, 44.3% of the overall decline in the U.S rates of death from coronary heart disease in 1980 and 2000 was attributed to population changes in levels of serum total cholesterol (24.2%) and systolic blood pressure (20.1%). The effects of clinical treatment on these risk factors were more modest, with statin and antihypertensive therapy accounting for 4.9% and 7.0% of the decline, respectively.”

“These observations were extended to long-term risk estimates, showing that changes in the prevalence of risk factor profiles strongly influence lifetime risk estimates in the general population,” the authors wrote.

Although the concept of primordial prevention is intriguing, the findings don’t obviate the need for maintaining a focus on primary prevention. The treatment effects mentioned by the investigators are small, but given the number of patients who get heart disease, they represent an enormous effect, Dr. Thompson said.

This study was supported by grants from the National Heart, Lung, and Blood Institute and the American Heart Association, and by funding from the Dedman Family Scholar in Clinical Care endowment at the University of Texas Southwestern Medical Center. Dr. Thompson is a consultant, has done research, or has received speaking honoraria numerous manufacturers of lipid-lowering drugs, including GlaxoSmithKline, Merck, Pfizer, and AstraZeneca. Individual author disclosures are available with the full text of the article at NEJM.org.

Subject Codes:
top_stories; diabetes; general_primary; cardiology; gerontology;

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January 25, 2012 05:00 PM EST

Medicare, Medicaid, Tort Reform in Play in Florida Primary

Wed, 25 Jan 2012 20:19 GMT

BY ALICIA AULT
Elsevier Global Medical News
Breaking News

Although the Republican primaries this year have been anything but predictable, one thing is fairly certain: Health care issues will play a more prominent role in the Florida primary on Jan. 31 than they have so far.

Florida is a coveted win for the GOP contenders in part because 50 delegates are at stake, but also because the state is more diverse – racially, ethnically, and politically – than Iowa, New Hampshire, and South Carolina, where primaries have already been held. As such, it’s considered a better reflection of the general election.

With its large elderly population and hard-hit economy, social welfare programs like Social Security, Medicare, and Medicaid are very important to Florida voters.

“Medicare is certainly the third rail in Florida among the sizeable senior population, but so too is Medicaid,” said Daniel A. Smith, Ph.D., professor of political science at the University of Florida, Gainesville.

Many seniors depend on both Medicare and Medicaid for their health care needs: Medicare for basic doctor and hospital care and Medicaid for long-term care, Dr. Smith pointed out.

That means Republican candidates should consider treading lightly when they talk about Social Security, Medicare, or Medicaid, he said, noting that in 1992, Ross Perot’s presidential bid was derailed in Florida after he said he would favor having wealthier Americans pay more for Social Security and Medicare.

“Retirees aren’t interested in dismantling the welfare state,” Mr. Smith said. “Even those Floridians of means are not interested in having their benefits cut.”

Health Care Platforms

At the Republican debate in Tampa on Jan. 23, Rick Santorum went after putative front-runner Mitt Romney for creating what he called a “government-run” health care plan when Mr. Romney was governor of Massachusetts. Mr. Santorum, a former senator from Pennsylvania, called that plan “RomneyCare,” a play on the dismissive “Obamacare” moniker that Republicans have given to the Affordable Care Act.

In the past, Mr. Santorum, who at press time was polling a distant third in Florida, has supported a plan by Rep. Paul Ryan (R-Wisc.) to essentially privatize Medicare. On his official campaign website, he says his first priority as President would be to repeal the Affordable Care Act. He also has said he would encourage the purchase of health insurance across state lines, push for block grants to states for Medicaid, and bolster health savings accounts. Mr. Santorum also backs medical liability reform.

Like Mr. Santorum, Newt Gingrich is calling for more competition in health care, block grants for Medicaid, and a repeal of the ACA. But the former Speaker of the House presents a more detailed plan for health care that includes reforming the Food and Drug Administration, investing more in health research, and putting a premium on quality of care.

Mr. Gingrich and Mr. Romney have traded the lead in Florida for the last several months, with Mr. Romney leading fairly broadly before the South Carolina primary on Jan. 21. Then, just as Mr. Romney won New Hampshire, Mr. Santorum was belatedly declared the winner in Iowa. Mr. Gingrich handily beat Mr. Romney in South Carolina, 40% to 28%.

According to the University of Florida’s Dr. Smith, Mr. Romney has actively courted health care executives in Florida. But it may not be enough to fend off continued brickbats thrown at him for the Massachusetts plan. He has repeatedly disavowed the notion that the plan was the model for the Affordable Care Act. On his website he says his first priority will be a repeal of Obamacare. Mr. Romney, like the other candidates, says he supports less regulation, more competition, and medical liability reform.

Although his platform makes no overt mention of Medicare, analysis by the Center on Budget and Policy Priorities noted that, if enacted, Mr. Romney’s proposal to cap total spending and balance the budget would lead to a 17%-24% cut to Medicare by 2016.

Interestingly, the American Federation of State, County and Municipal Employees has purchased air time in Florida to attack Mr. Romney for what it calls “Medicare fraud.”

The 30-second spot says that, while Mr. Romney worked for the Damon Corp., the company defrauded Medicare. The spot then goes on to morph Mr. Romney’s face into that of Florida Governor Rick Scott’s, with the tag line, “Sound familiar?”

Gov. Scott, a Republican, was the CEO of HCA (then called Columbia/HCA) during a period when the company was found guilty of defrauding Medicare. He was forced to resign and the company paid a record fine to the government. Gov. Scott has seen his approval ratings in Florida bottom out, in part because he proposed to finance public education through reductions in Medicaid payments to hospitals.

Gov. Scott has not endorsed any of the GOP candidates. “He knows that his poll numbers are quite toxic. As a result I don’t think his endorsement behooves anyone right now,” Dr. Smith said.

The Doctors Stand Clear

Several major physicians’ organizations have so far demurred on endorsing any of the candidates. A spokesperson said that the Florida Medical Association did not feel it was appropriate to even comment on a potential endorsement, given that its membership holds a variety of views.

Dr. John A. Gross, a member of the board of the Florida Academy of Family Physicians (that state’s chapter of the American Academy of Family Physicians), said that the FAFP would not be endorsing any candidates at this time either.

The FAFP is “looking for candidates that are willing to stand up for the patient,” said Dr. Gross, who chairs the group’s government relations committee. Family physicians would be interested in candidates who support the patient-centered medical home and new models that provide high quality care.

Tort reform also is a huge issue for Florida physicians, Dr. Gross noted. In a recent poll, physicians in the state estimated that 1 of every 3 health care dollars in Florida is spent on so-called defensive medical costs. The poll was conducted by Patients for Fair Compensation, a nonprofit established by the for-profit physician staffing company Jackson Healthcare.

Dr. Gross said that medical liability reform is a priority issue for the FAFP every year.

The latest bill to address tort reform was introduced in mid-January in the Florida House and Senate.

Abortion is also a hot-button issue in Florida. The state is regarded as anti-choice by NARAL Pro-Choice America.

Mr. Santorum describes himself as strongly pro-life. Mr. Gingrich has said he supports ending federal subsidies for abortion and defunding Planned Parenthood. Mr. Romney had a much-publicized change in position, seemingly going from supporting a woman’s right to choose to being against abortion. He does not have an official stance listed on his campaign website.

This is the first in a series of articles looking at the Republican presidential primaries through the eyes of physicians. Next up: The race moves on to Minnesota and Colorado, which hold their primaries Feb. 7.

Subject Codes:
nephrology_urology; infectious; top_stories; sports; ophthalmology; gastroenterology; mental_health; diabetes; dermatology; orthopaedics; pediatrics; general_primary; oncology; endocrinology; womens_health; pain; allergy; pulmonology; cardiology; rheumatology; surgery; otolaryngology; neurology; emergency_trauma; gerontology;

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January 25, 2012 03:19 PM EST

With Florida’s large elderly population and hard-hit economy, health care issues should play a prominent role in the Republican primary on Jan. 31.

Perspective - Clopidogrel Pharmacogenetics in the Clinic

Wed, 25 Jan 2012 15:19 GMT

BY HOWARD P. LEVY, M.D., PH.D.
Elsevier Global Medical News

As has been discussed previously in this column, the Food and Drug Administration label for clopidogrel now carries a black box warning about reduced efficacy in patients with diminished activity of the CYP450 enzyme 2C19.

Clopidogrel is a prodrug that needs to be converted to an active metabolite in order to inhibit platelet function. CYP2C19 is involved in a principal step in that activation process, and poor metabolizers who are treated with standard doses of clopidogrel tend to have increased rates of adverse cardiovascular events, compared with normal metabolizers. The label suggests that alternative treatment strategies for poor metabolizers should be considered, but there is still debate over exactly how to manage such patients. Furthermore, controversy exists regarding both the degree to which 2C19 variants explain the overall variation in clinical response to clopidogrel, and the role of genetic and functional testing in the use of clopidogrel.

While we await better scientific data to inform clinical decision making, we must do our best to determine practical applications of pharmacogenetics for our patients today.

The following are a few recent cases from my practice:

• Case 1. A 72-year-old man has vascular dementia resulting from recurrent strokes and small vessel cerebral ischemia. Clopidogrel (75 mg daily) was added to his daily aspirin for stroke prophylaxis 2 years ago. Unfortunately, his dementia progressed and cerebral MRI showed additional infarcts and progression of small vessel ischemic changes. His wife has been assisting with his medications, and he is not believed to be missing any doses. He used to take omeprazole, but that was stopped within a few months after the initiation of clopidogrel, and he is not currently taking any proton pump inhibitors (PPIs). He was started on fluoxetine for severe depression and anxiety about a year prior to starting clopidogrel, and the dose was gradually increased to 40 mg daily over the past few years. His depression is currently under good control.

The clopidogrel label includes a warning that PPIs reduce its pharmacologic activity by inhibiting 2C19 activity. Omeprazole is probably the most significant of the PPIs in this respect, but pantoprazole and lansoprazole have been reported to have some inhibitory effect on 2C19 activity, thus potentially limiting clopidogrel’s activation and efficacy. In addition to the PPIs, there are several other important 2C19 inhibitors, including fluoxetine, fluvoxamine and ketoconazole. A list of other substrates and inhibitors of 2C19 – as well as other CYP450 enzymes – is available.

In this case, two possible explanations for the failure of clopidogrel to prevent further cerebrovascular events are that he has a 2C19 genetic variant causing the poor metabolizer phenotype, and/or fluoxetine is inhibiting 2C19 and mimicking the poor metabolizer phenotype. However, his depression is doing well on fluoxetine, and he’d prefer not to change to a different antidepressant.

We therefore agreed to start by testing for a 2C19 variant.

If he is a poor metabolizer, then he is unlikely to respond to clopidogrel, regardless of the inhibitory effects of fluoxetine. In that scenario, the fluoxetine can be continued and a different drug – perhaps prasugrel – can be substituted for clopidogrel. On the other hand, if he has normal predicted 2C19 function, then it makes sense to change his antidepressant medication and continue clopidogrel.

• Case 2. A 71-year-old man is in good health, other than having gastroesophageal reflux, for which he takes omeprazole. He developed angina and was found to have single-vessel coronary artery stenosis. He received a drug-eluting stent, was taken off omeprazole, and was started on clopidogrel. The following day, a VerifyNow P2Y12 assay showed that his platelet function was adequately inhibited. CYP2C19 testing was not performed.

The FDA label suggests consideration of testing in association with clopidogrel therapy, but doesn’t make any specific recommendations. In situations in which it is pursued, this case presents an opportunity to examine the differences between a functional test and a DNA test.

Functional tests measure an actual biological end point, such as platelet inhibition. The Accumetrics VerifyNow test is one of several options that have been shown to correlate to some extent with treatment failure and cardiovascular events. They vary in cost, availability, standardization, simplicity, sensitivity, and specificity, and there is not yet agreement on the threshold for a suboptimal response.

Notwithstanding those limitations, their primary benefit is that they may provide a timely answer to the clinically relevant question of whether or not the drug is having the desired effect.

However, functional tests typically don’t identify the cause of the observed effect, which may be important if the desired outcome is not achieved. For clopidogrel failure, this could include 2C19 genetic variation, 2C19 inhibition from a PPI or other drug, missed doses, concurrent illness, or a variety of other genetic and environmental factors affecting absorption, distribution, metabolism, and elimination of the drug. Without this information, it can be difficult to determine how to improve therapy.

DNA tests typically identify risk for a clinical outcome, but often do not correlate 100% with that outcome. Identification of the most common 2C19 variants does correlate with likely failure of standard clopidogrel dosing, and some preliminary evidence-based treatment guidelines have been developed. However, the clinical importance of some of the rarer variants is not well enough understood.

Furthermore, a normal 2C19 result doesn’t guarantee adequate response to clopidogrel. The test could miss a rare but significant variant, or any of several other factors listed above could contribute to treatment failure.

The primary benefit of 2C19 testing is that it can help guide specific medication choices, not only for platelet inhibition, but also for any of the other drugs metabolized by this enzyme.

The benefits and limitations of functional vs. DNA tests are not limited to platelet function and clopidogrel metabolism. The same principles apply to most genetic questions.

For example, transferrin saturation is the best test to identify iron overload, but as a functional test it cannot distinguish secondary iron overload from hereditary hemochromatosis, nor identify which of several genes might be causing hemochromatosis in that particular patient. Genetic testing of the most common human hemochromatosis (HFE) gene can identify mutations that increase the risk of hemochromatosis, but most patients with mutations in this gene never develop clinical iron overload and don’t require any medical intervention.

Similarly, testing of the apo E gene can identify variants associated with increased risk of Alzheimer disease, but it takes functional neuropsychiatric testing to diagnose dementia, plus additional testing to differentiate the various causes of dementia.

In general, functional tests are good for initial diagnostic evaluation. When results fall within the normal (or desired) range, typically no further investigation is necessary, unless there is a genetic reason to suspect future disease, or something changes that might alter the clinical characteristic of interest. DNA tests offer predictive value, and can be helpful in elucidating the differential diagnosis when a functional test is abnormal.

This column, “Genetics in Your Practice,” appears regularly in Internal Medicine News, an Elsevier publication. Dr. Levy is at the division of general internal medicine and the McKusick-Nathans Institute of Genetic Medicine of Johns Hopkins University, Baltimore. He reports having no conflicts of interest.

Subject Codes:
cardiology;

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January 25, 2012 10:19 AM EST

©dra_schwartz/iStockphoto.com

PCI Trial Halted After FFR’s Benefit Shown

Tue, 24 Jan 2012 21:34 GMT

BY CATHERINE HACKETT
Elsevier Global Medical News
Breaking News

A large trial in the use of fractional flow reserve to guide percutaneous coronary intervention in patients with stable coronary disease has been halted because of the benefit shown in the patients who received the intervention.

The data safety and monitoring board of the FAME II trial recommended stopping the study early based on the positive results of an interim analysis. The board found a highly statistically significant reduction in hospital readmission and urgent revascularization in stable coronary disease patients who received a stent based on fractional flow reserve (FFR) assessment, compared with those treated with optimal drug therapy, and determined it would be unethical to continue to randomize patients to optimal medical therapy (OMT) based on the results so far, St. Jude Medical announced Jan. 18 in a statement.

The coordinating clinical investigator for the trial, Dr. Bernard De Bruyne, considered this a practice-changing step. The results show FFR “should be considered the standard of care for patients with coronary artery disease.”

“What we observed to date regarding urgent revascularizations validates the profound role that FFR-guided therapy has in improving patient outcomes,” Dr. De Bruyne, coordinating clinical investigator for the trial and a cardiologist at Onze-Lieve-Vrouw Clinic, Aalst, Belgium, said in St. Jude’s statement.

But such sweeping statements are premature, according to Dr. Eric Bates, professor of internal medicine at the University of Michigan Health System in Ann Arbor. “The data need to be reviewed by the scientific community.”

In FAME II, just over 1,200 patients had been randomized to either FFR-guided percutaneous coronary intervention or OMT in the trial, originally designed for 1,600 patients. Investigators will continue to follow enrolled patients, but no new patients will be added to the trial.

The devices used in the trial, the PressureWire Aeris and PressureWire Certus, combine measurements of pressure and temperature, enabling calculations of fractional flow reserve, coronary flow reserve, and an index of microcirculatory resistance.

The original FAME (Fractional Flow Reserve vs. Angiography for Guiding PCI in Patients with Multivessel Coronary Artery Disease) trial studied the procedure in patients who had already been selected for PCI. In that, patients whose PCI was guided by FFR had significantly reduced rates of the composite end point of death, nonfatal myocardial infarction, and repeat revascularization at 1 year, compared with those guided by angiography alone (N. Engl. J. Med. 2009;360:213-24). But the FAME II study, begun in 2010, is evaluating use of the tool for improving the benefits of stenting in the first place as an alternative to noninvasive medical therapy.

The latest PCI guidelines from the American College of Cardiology Foundation and the American Heart Association give FFR a tepid class IIa recommendation, saying it is reasonable for assessing angiographic intermediate coronary lesions (50%-70% diameter stenosis) and for guiding revascularization decisions in patients with stable ischemic heart disease (J. Am. Coll. Cardiol. 2011;58 [doi:10.1016/j.jacc.2011.08.007]). According to Dr. Bates, who was vice chair of the writing committee, fewer than 10% of PCI patients undergo FFR.

“Interestingly, there was no difference in death or MI rates” in St. Jude’s statement, “and no mention that the registered primary end point in clinicaltrials.org was the composite of death, MI, and unplanned hospitalization leading to urgent revascularization,” he said in an interview. Without the data to examine, the conclusions that it is “unethical to randomize patients to OMT alone” and that FFR has a “profound role” are at the very least hyperbole. “Moreover, the mechanism for decreasing hospital readmission and urgent revascularization rates needs to be explained to me,” he added.

“Adding a functional assessment to anatomic data makes great sense and is clinically encouraged.” To that end, the ISCHEMIA trial will soon start randomizing 8,000 patients with a LVEF of 35% or more and at least 10% cardiac ischemia. They will undergo blinded computed tomographic angiography to rule out high-risk left main disease or normal coronary arteries, and then will be randomized to catheterization and revascularization plus OMT or to optimal medical management alone, with revascularization reserved for worsening symptoms. The primary composite end point is cardiovascular death, MI, or adjudicated hospitalization for unstable angina, heart failure, or cardiac arrest. Secondary end points will include cost effectiveness and quality of life measures.

Dr. Bates had no relevant disclosures.

David Filmore of “The Gray Sheet” contributed to this report. Cardiology News and “The Gray Sheet” are both owned by Elsevier.

Subject Codes:
cardiology;

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January 24, 2012 04:34 PM EST

Aortic Regurgitation After TAVR Poses Threat

Mon, 23 Jan 2012 19:54 GMT

BY MITCHEL L. ZOLER
Elsevier Global Medical News
Breaking News

MIAMI BEACH (EGMN) – Now that transcatheter aortic valve replacement is available for routine U.S. use, interventionalists have focused on making the procedure better and safer, such as cutting the incidence of significant regurgitation through the replacement aortic valve.

Toward that end, researchers have developed a way to quickly and objectively assess the risk for aortic valve regurgitation based on the measurement of aortic blood pressures immediately after transcatheter valve replacement (TAVR). This new measure, the “aortic regurgitation index,” showed significant correlation with periprocedural aortic regurgitation as well as with patients’ 1-year survival following their procedure, Dr. Eberhard Grube said at ISET 2012, an international symposium on endovascular therapy.

Until now, “there has been no way to quantify aortic regurgitation; it’s subjective,” said Dr. Grube, professor and chief of cardiology and angiology at the Helios Heart Centre in Siegburg, Germany. The aortic regurgitation index (ARI) allows physicians “to quantify aortic regurgitation periprocedurally by objectively looking at the patient’s hemodynamics, regardless of the subjective evaluation of aortic insufficiency by angiography or by echo,” he said. “We can see the ARI and know what we need to do for postdeployment treatment.”

Dr. Grube and his associates set the ARI as equal to the patient’s diastolic aortic pressure minus the left ventricular end diastolic pressure, then divided by the aortic systolic pressure, and multiplied by 100.

For example, a patient with mild periprocedural aortic regurgitation might have an aortic diastolic pressure of 60 mm Hg, a left ventricular end diastolic pressure of 15 mm Hg, and an aortic systolic pressure of 150 mm Hg, which would produce an ARI of 30, showing that the patient had a low risk for dying during the subsequent year. In contrast, a patient with moderate or severe periprocedural aortic regurgitation could have an aortic diastolic pressure of 40 mm Hg, a left ventricular end diastolic pressure of 20 mm Hg, and an aortic systolic pressure of 120 mm Hg, which would produce an ARI of 16.7, flagging a higher mortality risk during the following year.

His group assessed the prognostic ability of the ARI in a series of 146 patients who underwent TAVR. The group included 124 patients with no or mild aortic regurgitation following TAVR and 22 who showed moderate or severe regurgitation. During 1-year follow-up, the 96 patients with a periprocedural ARI of 25 or greater had an 83% survival rate; the 50 patients with a periprocedural ARI of less than 25 had a survival rate of 54%, a statistically significant difference. The analysis also showed a significant correlation between the ARI and the severity of aortic regurgitation. Among patients with no discernible regurgitation, the average ARI was about 30, in those with mild regurgitation the average ARI was about 25, in patients with moderate regurgitation the average was about 18, and in patients with severe regurgitation the ARI averaged about 10.

One recently identified key to limiting aortic regurgitation following TAVR is proper valve sizing relative to the patient’s aortic annulus. “Appropriate valve sizing is likely the most important factor that will influence both the degree of perivalvular regurgitation and pacemaker need after TAVR,” said Dr. Jeffrey J. Popma in a separate talk at the meeting.

Until recently, many operators used transthoracic echocardiography for annulus sizing, but recently published evidence showed that imaging by CT or by MRI provide superior information, said Dr. Popma, director of interventional cardiology at Beth Israel Deaconess Medical Center in Boston. He cited a British report published last November that compared transthoracic echo, CT, and MRI in 202 patients who underwent TAVR, which found both CT and MRI superior to echo for annulus measurement prior to TAVR (J. Am. Coll. Cardiol. 2011;58:2165-73).

Dr. Grube said that he has financial relationships with Direct Flow, Claret, Biosensors, Medtronic, Mitralign, Boston Scientific, Cordis, Abbott Vascular, and InSeal. Dr. Popma said that he has financial relationships with Abbott, Boston Scientific, ev3 (Covidien), Medtronic, and Cordis.

Subject Codes:
cardiology;

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January 23, 2012 02:54 PM EST

Jeffrey J. Popma

Odds of Referral Nearly Doubled Over Decade

Mon, 23 Jan 2012 21:00 GMT

BY JANE ANDERSON
Elsevier Global Medical News
Breaking News

The odds that a patient visiting a physician would be referred to another physician – usually a specialist – rose by 94% between 1999 and 2009, while the absolute number of physician visits that resulted in a referral increased 159% during the same time frame, reflecting the rise in overall ambulatory visits during that decade.

The biggest increases were noted in referral rates from primary care physicians for patients with the following types of symptoms: cardiovascular (a referral rate of 8.5% in 1999-2002, increasing to 14.9% in 2006-2009), gastrointestinal (12.3% to 17.7%), orthopedic (12.4% to 16.5%), dermatologic (10.1% to 15.4%), and ear/nose/throat (4.5% to 8.5%), according to a study published Jan. 23 in the Archives of Internal Medicine.

Only physicians with ownership interests in their practices or those who obtained most of their income from managed care contracts had slower growth in referral rates.

The authors analyzed nearly 850,000 ambulatory patient visits in the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey, focusing on the decade 1999-2009.

It’s not entirely clear why referral rates are rising, according to Dr. Michael L. Barnett and his colleagues from Harvard Medical School, Boston.

“One possibility is that care is becoming increasingly complex, thereby requiring ever more care by specialized physicians,” Dr. Barnett said. Evidence for this theory includes the fact that physicians increased referrals for patients with cardiovascular or dermatologic symptoms, but not for those who presented with more general symptoms, such as those associated with viral illnesses.

“Likewise, chief concerns outside the traditional spectrum of primary care, such as ocular or gynecologic/breast symptoms, had a consistently high likelihood of referral from [primary care physicians] but had no significant change in referral rate,” they said (Arch. Intern. Med. 2012;172:163-170). “This suggests that some areas, such as cardiovascular and ear/nose/throat symptoms, may be increasingly outside the expertise or clinical portfolio of PCPs [primary care physicians] to manage alone. Other areas, such as gastrointestinal and orthopedic symptoms, had consistently increasing referral rates for PCPs and specialists, which may reflect increasing influence of those specialties in health care markets.”

Another possibility is that PCPs simply have too much to accomplish during limited visits, with increasing screening and preventive recommendations, the authors noted.

While appointment duration has not changed significantly in more than 20 years, “patients require more medications and frequently have one or more chronic medical conditions,” they said. “As a result... physicians, and in particular PCPs, may not have enough time to address each patient issue, resulting in increased rates of referrals.”

Finally, growing numbers of specialists – plus better availability of specialist physicians in many parts of the country – may influence referral rates, the authors said.

It’s not clear whether the increase in referrals overall reflects any kind of an increase in inappropriate referrals, Dr. Barnett said, adding that little literature exists on how to define appropriate referrals. “The complexity of referral appropriateness is compounded by the multiple roles that specialists can play in the care of a patient, ranging from consultative to procedural to co-managing a complex condition.”

The increase in referrals between 1999 and 2009 has implications for health care policy and health care spending in the United States, Dr. Barnett and his colleagues noted. “As federal and state policy makers consider policies for reforming the health care system, developing methods to measure referral appropriateness and using these to promote appropriate referrals may be an important strategy for controlling growth in health care spending.”

Coordinated Care Requires Payment Reform

Data showing a huge increase in the probability that an ambulatory visit will result in a referral are troubling, according to Dr. Mitchell H. Katz in remarks taken from his editorial that accompanied Dr. Barnett’s report (Arch. Intern. Med. 2012;172:100).

The study raises concerns about rising health care costs and fragmented care, Dr. Katz said. “But the real problem is that we have no idea what the data really mean.” The increase could stem from more complex caseloads, time-limited primary care appointments, demands from patients, or even malpractice concerns.

Dr. Katz, director of the Los Angeles County Department of Health Services, noted that e-referrals, in which primary care physicians and specialists communicate via shared electronic platforms supported by electronic health records, show some promise in helping eliminate costly visits and better coordinate care for patients by ensuring only necessary specialist visits occur.

Still, “for this new vision of patient referral to be fully realized, we will need financing reform,” Dr. Katz said. “As long as visits are reimbursed but electronic communication and cognitive time are not, referral visits will only grow. If, instead, payments for groups of patients are bundled, then generalists and specialists can organize their services in the most cost-effective way.”

The authors reported they had no conflicts of interest. Dr. Barnett reported no conflicts of interest.

Subject Codes:
gastroenterology; diabetes; general_primary; cardiology; otolaryngology;

http://www.imng.com

January 23, 2012 04:00 PM EST

Excitement Builds for Renal Denervation in Hypertension

Mon, 23 Jan 2012 19:05 GMT

BY MITCHEL L. ZOLER
Elsevier Global Medical News
Breaking News

MIAMI BEACH (EGMN) – The U.S. pivotal trial assessing renal denervation for blood pressure reduction began in October and a report on its final results won’t appear until next year, but excitement based on earlier study findings and the European clinical experience is already running high for this new approach to treating drug-resistant hypertension.

“Resistant hypertension is common, and is becoming more common despite a huge armamentarium of pharmacologic agents. The early literature [on renal denervation] is very impressive” for safety and efficacy, and the approach is plausibly “based on physiology,” Dr. Michael R. Jaff said at ISET 2012, an international symposium on endovascular therapy. Moreover, on top of the expected antihypertensive effect of renal denervation, recent results from a pilot, randomized controlled study with 50 hypertensive patients suggested that the intervention could also help normalize glucose metabolism and reverse type 2 diabetes in some patients.

Renal denervation “could arguably be the most exciting advance in interventional vascular medicine,” said Dr. Jaff, medical director of the vascular center at Massachusetts General Hospital in Boston. “People’s imaginations are running wild about the potential implications of this type of therapy for a whole host of patients. In the near term I’m incredibly bullish [about this treatment] and in the far term I’m even more enthusiastic.”

In addition to the clinical efficacy that renal denervation so far has shown, it has the pluses of being relatively simple and easy to do, easy to learn, and fairly quick; the procedure involves modestly priced equipment and appears very safe as well, noted Dr. Horst Sievert, an interventional cardiologist who collaborated on one of the efficacy trials and now routinely performs renal denervations at the cardiovascular center of Saint Katharinen Hospital in Frankfurt, Germany.

The Symplicity Renal Denervation System, developed by Ardian, which is now owned by Medtronic, has been available for routine use in Europe and Australia since 2010. The U.S. pivotal trial, Symplicity HTN-3 (Renal Denervation in Patients With Uncontrolled Hypertension), plans to enroll 530 patients at 60 U.S. centers and should be completed by March of next year.

The procedure, which requires just a flexible catheter and radiofrequency generator, delivers four to eight low-power treatments along the length of both main renal arteries using a 6F sheath, targeting the renal nerves in the adventitia of the renal arteries and producing reduced sympathetic activity and renin release. According to Dr. Sievert, the typical procedure takes 45-60 minutes, and is successful in significantly reducing systolic and diastolic pressure in 75%-80% of drug-refractory patients. The worldwide case experience so far has led to few complications, no reported thrombus formations, no detrimental effects on renal blood flow or function, and no reported cases of severe hypotension following treatment, he said.

“I believe that renal denervation will become as important as PCI [percutaneous coronary intervention] or PTA [percutaneous transluminal angioplasty],” said Dr. Sievert, director of the cardiovascular center and also on the faculty of the University of Frankfurt.

“The risks are so few and the complication rate so low that it’s not worth figuring out which patients will respond and who won’t. I would just do the treatment and see if the patient responds,” Dr. Sievert said at the meeting. No explanation exists as to why some patients don’t respond, and no marker exists to distinguish patients who will respond and those who won’t.

The largest systematic assessment of the antihypertensive impact of renal denervation came in a randomized trial, Symplicity HTN-2, with 106 patients, which was sponsored by Ardian and published in 2010. All patients had an entry systolic pressure of at least 160 mm Hg (or at least 150 mm Hg if they also had type 2 diabetes) despite current treatment with at least three antihypertensive medications. At 6 months after treatment, the 52 patients treated with denervation had an average blood pressure reduction of 32/12 mm Hg, compared with an average systolic pressure rise of 1 mm Hg and no average diastolic change in the 54 control patients (Lancet 2010;376:1903-9).

In the denervation group, 84% of patients had at least a 10-mm Hg drop in their systolic pressure 6 months after treatment compared with 35% of the control patients having this response, and 39% of the denervation patients had their systolic pressure fall below 140 mm Hg at 6 months compared with 6% of control patients. A subsequent report on a total of 153 patients treated with renal denervation documented that the blood pressure reductions seen at 6 months persisted out to 2 years (Hypertension 2011;57:911-7).

Striking as this effect was, perhaps even more notable was a report last year from a separate pilot study that randomized 50 patients who met the same definition of refractory hypertension. In addition to showing similar blood pressure results in the denervated patients, the researchers on this study also looked at several measures of glucose metabolism. At 3 months after intervention, the 37 denervated patients had an average 9% cut in their fasting blood glucose level and an average 12% drop in their average fasting blood insulin levels, both statistically significant changes from baseline, compared with no significant change in the 13 control patients. The percent of patients with normal glucose tolerance rose by 11% in the denervated group, and dropped by 7% in the control group. The authors of the report concluded that renal sympathetic activity plays a role in insulin resistance (Circulation 2011;123:1940-6).

Future studies will likely examine the possible impact of renal denervation on heart failure and on obstructive sleep apnea, noted Dr. Jaff.

Dr. Jaff said that he has financial relationships with several cardiovascular device companies including Medtronic Hansen Medical and Medtronic Vascular. Dr. Sievert said that he has financial relationships with several cardiovascular device and pharmaceutical companies including Ardian and Medtronic.

Subject Codes:
nephrology_urology; cardiology;

http://www.imng.com

January 23, 2012 02:05 PM EST

Anticipation is building for the final results of a pivotal trial on renal denervation for blood pressure reduction.

EMA to Review Fingolimod Following Deaths

Fri, 20 Jan 2012 15:51 GMT

BY JENNIE SMITH
Elsevier Global Medical News
Breaking News

The European Medicines Agency said Jan. 20 that it has begun a review of fingolimod, a drug used to treat multiple sclerosis.

The review was initiated, the EMA said, over patient reports of cardiac problems and one unexplained death of a U.S. patient following initiation of fingolimod treatment. The agency said that six other unexplained deaths (including three cases of sudden death) have been reported following initial treatment, and that additional reports include three deaths due to heart attack and one due to disruption of the heart rhythm.

Fingolimod (Gilenya, Novartis) has had marketing authorization in the European Union since March 2011, and was approved by the Food and Drug Administration in September 2010 as the first oral agent to reduce relapses of MS. Fingolimod is administered in 0.5-mg capsules, taken once daily.

Some 30,000 patients have received fingolimod worldwide, the EMA said. The drug works by targeting blood cells in lymph nodes, reducing their migration to the brain and spinal cord.

That the drug carries bradycardia risks is known, and current labeling advises in-clinic monitoring for 6 hours following the first dose. However, the EMA is now advising physicians to intensify their monitoring of patients by initiating electrocardiogram monitoring before treatment, and then every hour for 6 hours after the first dose, while measuring blood pressure and heart rate every hour.

“After 6 hours, any patients with clinically important heart-related effects, such as bradycardia ... or atrioventricular block ... should continue to be managed and monitored until their condition has improved,” the EMA said in a written statement Jan. 20.

Fingolimod’s manufacturer has agreed to supply the EMA with results of ongoing investigations into the drug’s cardiovascular risks, the EMA said. The agency said it expects to finalize its review in March.

Subject Codes:
cardiology; neurology;

http://www.imng.com

January 20, 2012 10:51 AM EST

First U.S. Fibromuscular Dysplasia Registry Yields New Clues

Wed, 18 Jan 2012 16:03 GMT

BY MITCHEL L. ZOLER
Elsevier Global Medical News
Breaking News

MIAMI BEACH (EGMN) – The mystery shrouding fibromuscular dysplasia, a clinically important and surprisingly prevalent vascular disease of unknown etiology, began to lift with initial findings from 339 patients enrolled in the first U.S. registry for the disease.

Baseline observations from the U.S. Registry for Fibromuscular Dysplasia (FMD), which enrolled its first patient in 2008 and currently has women as 91% of enrolled patients, show that the disease first occurs across a broad swath of age groups, with an age at first diagnosis ranging from 5 to 83 years old. In addition to the distinctive “string of beads” arterial fibrosis appearance that defines the disease and is apparent on imaging, and which usually occurs in the renal or carotid artery, or both, 19% of patients also had a dissection in an artery somewhere in their body (14% with a dissection in a carotid artery) and 17% had an arterial aneurysm somewhere (5% with a renal artery aneurysm and 4% with a carotid aneurysm).

These dissection and aneurysm prevalence rates had not previously been appreciated to run so high in FMD patients. “It suggests a diffuse arteriopathy that can present in several different ways,” Dr. Jeffrey W. Olin said at ISET 2012, an international symposium on endovascular therapy.

Another notable finding was that, besides hypertension, which was the most common presenting manifestation of FMD (seen in 66% of the registry patients at initial diagnosis), other common presenting symptoms included significant, often migraine-like headache in 53%, pulsatile tinnitus (a whooshing sound patients hear) in 30%, and dizziness in 28%. The high prevalence of headache in FMD had been “first reported 30 years ago, but sort of got lost,” Dr. Olin said in an interview.

“A patient can have normal blood pressure and normal-appearing carotid and renal arteries but have terrible headaches and have FMD. Why? We don’t know. We have no idea what causes the headaches,” said Dr. Olin, a cardiologist who is professor of medicine and director of vascular medicine at Mount Sinai Medical Center in New York. Four percent of the registry patients had no symptoms on presentation; physicians found their FMD incidentally during imaging examinations for other reasons.

Other flags to trigger suspicion of FMD include hypertension that begins before age 35 (although it can also start later in life), treatment-resistant hypertension, epigastric bruit and hypertension, renal infarction, cervical bruit in a patient less than 60 years old, transient ischemic attack or stroke in a patient less than 60 years old, or an aortic aneurysm in a patient less than 60 years old.

Perhaps the most surprising new finding so far from the registry is evidence for a strong family history of cardiovascular disease, with 81% of first- or second-degree relatives of FMD patients having hypertension, 59% with hyperlipidemia, 53% with a history of a stroke, 22% with an aneurysm, and 21% with a history of sudden death. The prevalence of a first- or second-degree relative also having a diagnosis of FMD was 7%, not much higher than the currently estimated 4% prevalence of FMD in the general population.

Dr. Olin and his associates from the registry hypothesize that patients who develop FMD have an as-yet unidentified genetic predisposition that interacts with an environmental trigger. His hope is that, by continuing to expand the registry and by receiving substantially more research support than FMD now gets, a more concerted research effort can address the genetic questions raised by the family-history findings.

Current treatment of FMD is symptom driven and usually focuses on trying to resolve patients’ hypertension, which is often treatment resistant.

“FMD is potentially treatable for hypertension,” with endovascular treatment of affected renal arteries the standard intervention for patients with resistant hypertension, Dr. Robert A. Lookstein said in a separate talk at the meeting. Hypertension cure rates from balloon angioplasty, however, are “surprisingly low” – 45% in one meta-analysis – probably because of suboptimal interventional treatment, said Dr. Lookstein, chief of the division of interventional radiology at Mount Sinai.

Assessing a patient’s renal arteries before and during treatment using intravascular ultrasound (IVUS) and a pressure wire provides the key to successful resolution of hypertension by renal-artery angioplasty in FMD patients, he said.

These two techniques, especially pressure-wire measurements, allow the operator to assess the patient’s renal arteries before and during treatment to determine whether the intervention is having a meaningful effect. “You can’t tell [whether the angioplasty produced benefit] by the angiography appearance alone,” he cautioned. “You need to be compulsive with IVUS and measuring pressure gradients to determine where to start treatment and when to stop.”

The U. S. Registry for FMD began with seven U.S. centers enrolling patients and now involves 10 centers and has enrolled more than 500 patients. The first 339 enrollees included 44% who were patients at the Cleveland Clinic and 20% who were patients at Mount Sinai.

The average age of the enrolled patients at first symptom appearance was 47 years old; first diagnosis did not occur until an average of more than 4 years later, at an average age of 52 years old.

Vascular bed involvement among the first registry patients included one or both renal arteries in 69%, at least one extracranial carotid in 62%, vertebral arteries in 19%, and mesenteric arteries in 12%. At the time of enrollment, 7% of patients had a history of coronary artery disease and 10% had a history of stroke. The arterial fibrosis characteristic of FMD notably appears in portions of the renal and carotid arteries where atherosclerotic disease usually does not occur – in the distal renal artery and in the distal carotid, “higher than physicians usually look when they do carotid ultrasound” examinations, Dr. Olin said.

When he finds carotid fibrosis, Dr. Olin starts those patients on a daily aspirin, although the benefit of this strategy hasn’t been proven. If carotid lesions are substantial, treatment by angioplasty is possible; carotid stenting is not used on FMD patients, nor is endarterectomy, as there is no atherosclerotic plaque to remove, he said.

Dr. Olin said that he has been a consultant to Merck, and that he chairs the advisory board of the Fibromuscular Dysplasia Society of America. Dr. Lookstein said that he has been a consultant to Medrad and Cordis.

Subject Codes:
nephrology_urology; general_primary; cardiology; neurology;

http://www.imng.com

January 18, 2012 11:03 AM EST

Dr. Robert A. Lookstein

Novel Antiplatelet a Bridge Between Thienopyridine and CABG

Tue, 17 Jan 2012 21:00 GMT

BY MARY ANN MOON
Elsevier Global Medical News
Breaking News

Intravenous cangrelor may prove to be a useful “bridge” in patients awaiting nonemergency CABG who must first discontinue their regular antiplatelet therapy, according to the results of the Maintenance of Platelet Inhibition With Cangrelor (BRIDGE) trialreported in the Jan. 18 issue of JAMA.

The practice of discontinuation of antiplatelet therapy is associated with significant morbidity and mortality; in patients who have coronary stents, it raises the risk of stent thrombosis that often leads to myocardial infarction and death. “Cessation of thienopyridine treatment for nearly a week before surgery, with patients not hospitalized or monitored but carrying an excess risk of major ischemic events, has been a troubling and not infrequent problem for clinicians, because it is estimated that approximately 5% of patients will require some type of surgery within the first 12 months after stent implant or [acute coronary syndrome] diagnosis,” said Dr. Dominick J. Angiolillo of the department of cardiology, University of Florida, Jacksonville, and his associates.

In this multicenter clinical trial sponsored by the drug’s maker, cangrelor “achieved and maintained target levels of platelet inhibition known to be associated with a low risk of thrombotic events compared with placebo, without a significant excess in bleeding complications,” the investigators noted.

Cangrelor is an investigational nonthienopyridine adenosine triphosphate analogue that acts as an antagonist of the P2Y12 receptor. It is characterized by “rapid, potent, predictable, and reversible platelet inhibition,” and its extremely short half-life (3-6 minutes) allows “rapid offset of effect.”

The investigators hypothesized that cangrelor would allow patients who must discontinue antiplatelet therapy prior to cardiac surgery, especially if they’re taking a P2Y12 inhibitor such as ticlopidine, clopidogrel, or prasugrel, to go off their usual drug without raising their risk for thrombotic events. They tested this hypothesis in a two-part trial.

The first part was an open-label dose-finding study involving 11 adults, which concluded that the optimal intravenous dose needed to maintain antiplatelet activity without raising bleeding risks was 0.75 mcg/kg per minute.

In the second part of the trial, 210 patients awaiting CABG at 34 medical centers around the world were randomly assigned to receive either cangrelor (106 subjects) or placebo (104 subjects) after thienopyridines were discontinued and throughout the preoperative period – that is, until 1-6 hours before surgical incision. Platelet function was assessed before, during, and after the infusion.

The mean interval between discontinuation of thienopyridines and infusion of the study drug was 29 hours, and the mean duration of the infusion was approximately 3 days.

The primary end point was the percentage of patients who showed platelet reactivity of less than 240 P2Y12 Reaction Units (PRUs) throughout the infusion of the study drug. “This level approximated the levels of platelet reactivity expected to be maintained if a thienopyridine had not been discontinued,” the investigators explained.

This end point was met by 99% of the cangrelor group but only 19% of the placebo group. It was achieved independently of patients’ usual dose of thienopyridines and independently of the length of time since thienopyridines were discontinued, Dr. Angiolillo and his colleagues said (JAMA 2012;307:265-74).

Moreover, cangrelor did not raise the rate of excessive bleeding related to CABG surgery. This safety end point occurred in 22 patients: 11.8% of the cangrelor group and 10.4% of the placebo group, a nonsignificant difference.

The number of minor bleeding events was numerically higher with cangrelor but did not reach statistical significance. Other adverse events, including dyspnea and laboratory abnormalities, also were comparable between the two groups. This favorable safety profile, even with prolonged infusion of up to 7 days, was “reassuring,” the researchers noted.

Ischemic end points prior to surgery were low in both groups, occurring in 2.8% (3 of 106) and 4.0% (4 of 101) of patients in the cangrelor and placebo groups.

“These observations support the hypothesis that intravenous cangrelor is a feasible management strategy, providing prolonged platelet P2Y12 inhibition in patients who must wait for cardiac surgery after thienopyridine discontinuation,” they said.

This study was sponsored by the Medicines Company. Dr. Angiolillo reported ties to Bristol-Myers Squibb, Sanofi-Aventis, Eli Lilly, Daiichi Sankyo, AstraZeneca, Portola, Novartis, Medicure, Accumetrics, Arena Pharmaceuticals, Merck, Evolva, and Abbott Vascular, and his associates reported ties to numerous other industry sources.

Subject Codes:
top_stories; cardiology; surgery;

http://www.imng.com

January 17, 2012 04:00 PM EST

Benchmarks Discerned for In-Hospital VTE After Hip, Knee Arthroplasty

Tue, 17 Jan 2012 21:00 GMT

BY MARY ANN MOON
Elsevier Global Medical News
Breaking News

For the first time, researchers say they have established benchmarks for the rates of in-hospital venous thromboembolism that occur after total or partial hip arthroplasty and after total or partial knee arthroplasty, according to a report Jan. 18 in JAMA.

In a meta-analysis of 47 studies that documented venous thromboembolism (VTE) event rates in nearly 45,000 patients who received recommended prophylaxis during hospitalization for knee or hip arthroplasty, investigators estimated that approximately 1 in every 100 patients undergoing knee arthroplasty and 1 in every 200 undergoing hip arthroplasty will develop symptomatic VTE before they are discharged.

“These estimates are of value to individual patients and clinicians in the consideration of risks and benefits” of the two procedures. They also are important because rates of in-hospital VTE are increasingly used as indicators of patient safety at individual medical centers, even though the expected background rates haven’t been established until now, said Jean-Marie Januel, a registered nurse with the Institute of Social and Preventive Medicine, Lausanne (Switzerland) University Hospital, and his associates.

“Large numbers of patients worldwide undergo hip and knee replacement procedures annually, and VTE is a widely acknowledged complication. Yet no estimate of symptomatic VTE risk prior to hospital discharge is available from the literature that can be conveyed to patients in the informed consent process,” they noted.

Mr. Januel and his colleagues performed a systemic search of the literature to identify studies performed between 1996 and 2011 in which subjects undergoing either hip or knee arthroplasty received VTE prophylaxis according to published guidelines, including either low-molecular-weight heparin or inhibitors of factor Xa or IIa. They found 41 randomized clinical trials and 6 observational studies to include in the meta-analysis.

A total of 22 of the studies were performed in Europe, 14 were in North America, and 11 were in other regions. The mean duration of follow-up after either surgery was 13 days.

This included 21 studies of partial or total hip arthroplasty, 20 of partial or total knee arthroplasty, and 6 studies of both procedures, with a total of 44,844 subjects.

There were 443 cases of symptomatic postoperative VTE that developed before hospital discharge: 288 in the 23,475 knee patients and 155 in the 23,475 hip patients. This included 182 cases of deep vein thrombosis in the knee patients and 93 in the hip patients, as well as 106 cases of pulmonary embolism in the knee patients and 43 in the hip patients.

The pooled incidence rates of VTE were approximately 1% after knee arthroplasty and approximately 0.5% after hip arthroplasty. This means that the background rate of VTE is approximately 1 in 100 knee patients and 1 in 200 hip patients, the investigators said (JAMA 2012;307:294-303).

When the data were broken down by type of VTE, the pooled incidence rates were 0.26% for deep vein thrombosis and 0.14% for pulmonary embolism after knee arthroplasty. The corresponding rates were 0.63% for deep vein thrombosis and 0.27% for pulmonary embolism after hip arthroplasty.

“Given that these rates are based on the results of rigorous studies, they may represent a lower incidence than actual rates observed in clinical practice, in which patients are selected less rigorously and prophylaxis is administered less assiduously,” Mr. Januel and his associates noted.

The pooled incidence rates of deep vein thrombosis were lower for both knee patients and hip patients when factor Xa or IIa inhibitors, rather than low-molecular-weight heparin, were given for prophylaxis. “However, we cannot make assertions regarding comparative efficacy among treatments, because our meta-analysis did not directly compare [these agents] as an efficacy meta-analysis would have done,” they said.

In-Hospital Not as Telling as Post-Discharge VTE Rates

The in-hospital VTE rates reported by Januel et al may be “suboptimal” for assessing both patients’ risks and a facility’s performance in patient safety, as the investigators proposed, said Dr. John A. Heit of the division of cardiovascular diseases at the Mayo Clinic, Rochester, Minn.

The period of VTE risks extends far beyond the hospital stay, with as many as 76% of VTE events occurring during the 3 months following hospital discharge. “From the perspective of the patient contemplating elective total hip replacement or total knee replacement,” the 3-month rate rather than the in-hospital rate of VTE is more important in weighing risks and benefits, he said in an editorial accompanying Mr. Januel’s report (JAMA 2012;307:306-7).

And it can be argued that this cumulative rate of VTE is also more important for the purpose of assessing a facility’s performance, Dr. Heit added.

This study was supported by Alberta Innovates Health Solutions, a government research funding agency, and the International Methodology Consortium for Coded Health Information, a collaboration of health sciences researchers to promote quality of care. Dr. Heit reported ties to Daiichi Sankyo, GTC, Ortho-McNeil-Jansen, the National Heart, Lung, and Blood Institute, the National Human Genome Research Institute, the National Institutes of Health, the Centers for Disease Control and Prevention, and the Mayo Foundation.

Subject Codes:
top_stories; cardiology; rheumatology; surgery; gerontology;

http://www.imng.com

January 17, 2012 04:00 PM EST

Local, Regional Anesthesia Surpass General for AAA EVAR

Tue, 17 Jan 2012 19:17 GMT

BY MITCHEL L. ZOLER
Elsevier Global Medical News
Breaking News

MIAMI BEACH (EGMN) – Local and regional anesthesia are better options than is general anesthesia for patients undergoing endovascular repair of an abdominal aortic aneurysm, based on findings from a registry with nearly 1,200 patients.

Both local anesthesia and regional anesthesia each surpassed general anesthesia in two periprocedural measures: significantly reducing procedure time, and significantly reducing postoperative hospitalization, Dr. Rutger A. Stokmans said at ISET 2012, an international symposium on endovascular therapy.

In addition, both local and regional anesthesia led to trends in reduced rates of major adverse events during the 30 days following surgery, although these differences did not reach statistical significance. All three anesthesia types linked with similar rates of both technical and clinical success of the aneurysm repairs. Regional anesthesia also led to a significantly lower rate of ICU admission, compared with both general and local anesthesia; local anesthesia showed no significant difference for this measure, compared with general anesthesia.

Based on these findings, local or regional anesthesia should be preferred when performing endovascular aneurysm repair (EVAR), whereas general anesthesia should usually be avoided, said Dr. Stokmans, a vascular surgeon at Catharina Hospital in Eindhoven, the Netherlands.

These findings support the most recent anesthesia recommendations of the European Society for Vascular Surgery, which in 2011 guidelines for managing abdominal aortic aneurysms (AAA) cited local anesthesia as preferred for EVAR, with regional or general anesthesia reserved for patients with contraindications for local anesthesia, he said (Euro. J. Vasc. Endovasc. Surg .2011;41[suppl. 1]:S1-S58). The most recent guidelines for AAA management from the Society for Vascular Surgery suggested using local or regional anesthesia over general anesthesia, he added (J. Vasc. Surg. 2009[suppl.]:50:S2-S49).

But despite these recommendations, the most commonly used anesthesia type worldwide for EVAR repair of AAA has been general anesthesia, followed by regional anesthesia, with local treatment used least often, according to the registry data reported by Dr. Stokmans. Among the 1,199 patients enrolled in ENGAGE (Endurant Stent Graft Natural Selection Global Postmarketing Registry) during March 2009 to December 2010 in 30 countries on five continents, 749 (62%) underwent their EVAR with general anesthesia, 325 (27%) with regional, and 125 (10%) with local anesthesia. (Percentages do not add up to 100% because of rounding.)

The registry data also showed striking regional variations in anesthesia use, with general anesthesia used on about 90% of patients in Canada, Australia, and New Zealand, and on about 70% of patients in Scandinavian countries and the United Kingdom. But in Central Europe, regional anesthesia – used on nearly 70% of EVAR patients – dominated. The only region favoring local anesthesia was South America (Argentina, Columbia, and Uruguay), where about 50% of patients received local, but more than 40% received general anesthesia, he said. The registry contained no U.S. patients, although the Endurant AAA stent graft system is marketed in the United States.

The average age of the EVAR patients in the registry was about 73 years. Those patients who underwent general anesthesia were significantly older, by an average of about 18 months, compared with those who received local or regional anesthesia.

The proportions of patients undergoing general, regional, or local anesthesia were similar in the subgroups of patients with American Society of Anesthesiologists (ASA) physical status scores of 1, 2, or 3. However, among the highest-risk patients included in the study – those with an ASA score of 4 – a significantly greater proportion of patients received general anesthesia. The multivariate models used in the analysis, therefore, were adjusted for age and for ASA score. About 42% of patients were in ASA class 2, and another 42% in class 3.

All patients were hemodynamically stable at the time of their enrollment. The maximum AAA diameter of registry patients was 6 cm, and about 88% of patients had an AAA diameter greater than 5 cm.

Average procedure times were 106 minutes in the general anesthesia patients, 95 minutes in the regional patients, and 81 minutes in the local anesthesia patients – statistically significant differences among the three groups.

The average postoperative hospitalization was 5.2 days in the general anesthesia patients, 4.3 days in the regional patients, and 3.6 days in the local anesthesia patients, differences that were statistically significant among each of the three groups.

The rate of technical surgical success was 98% in all three subgroups, and the rate of clinical success reached 97%-98% in all three groups.

The rates of major adverse events during the 30 days following surgery were 5.1% in the general anesthesia patients, 3.2% in the local patients, and 2.2% in the regional anesthesia patients. None of these differences reached statistical significance. Major adverse events included death, MI, stroke, renal failure, blood loss greater than 1 L, and bowel ischemia. No patients developed paraplegia or respiratory failure.

Postoperative ICU admission occurred for 27% of the regional anesthesia patients, 35% of the general patients, and 42% of the local anesthesia patients. The rate among the regional patients was significantly less than in the other two groups, but the difference in rates between the general and local anesthesia patients did not reach statistical significance.

The ENGAGE registry was organized and sponsored by Medtronic, which markets the Endurant stent. Dr. Stokmans and his associates received an unrestricted research grant from Medtronic. Dr. Stokmans said that he had no other disclosures.

Subject Codes:
top_stories; cardiology; surgery;

http://www.imng.com

January 17, 2012 02:17 PM EST

Rutger A. Stokmans

Cardiac Screening Is Not Routine Before Prescribing Stimulants

Mon, 16 Jan 2012 05:01 GMT

BY HEIDI SPLETE
Elsevier Global Medical News
Breaking News

Twenty-four percent of 525 pediatricians surveyed agreed that children with attention-deficit/hyperactivity disorder should undergo cardiac screening before taking stimulants, according to a study published online Jan. 16 in Pediatrics.

Although postmarketing reports during the past decade have shown cases of sudden cardiac death (SCD) in children with attention-deficit/hyperactivity disorder (ADHD) who were taking stimulants, findings from studies specifically addressing the topic have been inconsistent, said Dr. Laurel K. Leslie of Tufts Medical Center, Boston, and colleagues.

These studies have been undertaken in the wake of various recommendations for evaluation of cardiac status prior to starting stimulant treatment. In 2008, the American Heart Association “released a policy statement widely interpreted as recommending the routine use of electrocardiograms (ECGs) to evaluate children” prior to starting treatment with stimulant medication (Circulation 2008;117:2407-23).

As a clarification of that policy statement, the American Academy of Pediatrics (AAP) and the American Heart Association subsequently published a joint statement, which was endorsed by the American Academy of Child and Adolescent Psychiatry, that revised the American Heart Association’s original recommendation of the ECG. The joint statement stated that physicians should perform in-depth cardiac history and physicals (H&P) prior to starting stimulant treatment and get ECGs for children with positive findings. It noted that getting an ECG was a Class IIa recommendation so it is reasonable for a physician to consider an ECG, but not mandatory.

Then, the AAP stated in a 2008 policy statement that medications used to treat ADHD had not been shown to cause SCD, and there was not sufficient evidence to justify obtaining routine ECGs before starting treatment with stimulants. The AAP concluded that “until these questions are answered, a recommendation to obtain routine ECGs for children receiving ADHD medications is not warranted” (Pediatrics 2008;122:451-3).

In Dr. Leslie’s current study, 75% of the survey respondents agreed that physicians have a responsibility to inform families about the possible risk of SCD before children begin treatment with stimulants. However, only 30% agreed that the risk of a potential lawsuit was high enough to warrant cardiac screening (Pediatrics 2012;129:222-30).

In addition, 36% of the respondents agreed that informing families about a possible SCD risk might deter them from giving the stimulants to their children.

As part of the survey, each of the respondents reported the cardiac screening practices for his or her most recent patient with ADHD. Nearly all respondents (93%) completed a routine history and physical, and 71% collected an in-depth cardiac history, while 48% completed an in-depth cardiac history and physical.

Less than half (46%) of the physicians discussed cardiac risks with families of a recent patient with ADHD, although most (93%) of the respondents discussed weight loss or appetite suppression as a side effect of stimulants, 87% discussed sleep disturbance, and 75% discussed affective symptoms such as moodiness, irritability, and suicidality.

A total of 77 respondents (15%) reported ordering an ECG for their most recent patient; 42 of these did so because it was standard in their practices. Only 16 (21%) of the physicians who ordered ECGs reviewed the results themselves.

There was a general lack of comfort with cardiac screening procedures. A total of 71% of respondents said that their ability to interpret a pediatric ECG was a barrier to screening, and 18% said that their ability to perform an in-depth cardiac history and physical was a barrier. The respondents reported other barriers including lack of local specialists (18%), a long wait to see a specialist (37%), and patients’ inability to pay for care (52%).

In a multivariate analysis, certain associations emerged among attitudes, barriers, and physician practices, the researchers wrote. “Legal liability and physician responsibility to inform families of SCD risk were positively associated with an in-depth cardiac H&P, whereas barriers in ability to perform an in-depth cardiac H&P were negatively associated,” they noted.

The findings suggest that balancing the potential benefits of stimulants for ADHD children with the obligation to inform families of a possible SCD risk remains a challenge for pediatricians, the researchers said.

“Shared decision-making extends informed consent by not only exchanging information about treatment options, risks, and benefits, but also by sharing viewpoints so that patients, families, and physicians become aware of each other’s perspectives with the goal of achieving a mutually agreed on treatment plan,” Dr. Leslie and colleagues wrote.

The survey was mailed to 1,600 randomly selected AAP members who provide direct patient care to children aged 5-17 years with ADHD. Pediatricians who were retired, trainees, or not based in the United States were excluded. Most who responded were female, non-Hispanic/white, and practicing for an average of 18 years.

The study was limited by the lower-than-expected response rate, the lack of information about the resources available in each practice, and the lack of perspective from families. But the study is the first to ask pediatricians about this topic specifically, and the findings reinforce the ongoing controversy over the potential cardiac risks associated with stimulant use by children with ADHD, Dr. Leslie and colleagues noted.

Dr. Leslie and colleagues reported having no relevant financial disclosures. The study was funded by the National Institutes of Health.

Subject Codes:
top_stories; mental_health; pediatrics; cardiology;

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January 16, 2012 12:01 AM EST

CORRECTION: D-Dimer May Be Marker of VTE Risk

Fri, 13 Jan 2012 19:12 GMT

Elsevier Global Medical News

The article “D-Dimer May Be Marker of VTE Risk” (published Jan. 5, 2012) misstated D-dimer levels. The baseline median D-dimer level was 0.94 mg/L in all patients. The baseline D-dimer level was higher in patients who experienced a primary efficacy outcome event, compared with those who did not have such an event (a median of 1.98 mg/L vs. 0.92 mg/L).

Subject Codes:
cardiology; surgery;

http://www.imng.com

January 13, 2012 02:12 PM EST

Marathon Runners Are at Low Risk of Cardiac Arrest

Wed, 11 Jan 2012 22:00 GMT

BY MARY ANN MOON
Elsevier Global Medical News
Breaking News

Marathon runners’ risk of cardiac arrest is relatively low – equivalent to or lower than that of other athletes engaged in vigorous activity, according to a report in the Jan. 12 issue of the New England Journal of Medicine.

The number of cardiac arrests related to marathon (26.2-mile) and half-marathon (13.1-mile) races has increased in recent years, but that is largely explained by the increase in the number of people who have taken up the sport, said Dr. Jonathan H. Kim of the division of cardiology, Massachusetts General Hospital, Boston, and his associates.

“The growth of long-distance running has been accompanied by studies documenting post-race cardiac dysfunction and numerous reports of race-related cardiac arrest. These unexpected tragedies attract considerable media attention and have led to concerns regarding the health risks of this activity,” the researchers wrote.

Until now, no large studies have examined the incidence, clinical profiles, and outcomes of cardiac arrests that occur during or immediately after long-distances races. The Race Associated Cardiac Arrest Event Registry (RACER) collected data to facilitate such studies. It included information on all marathon or half-marathon races held in the United States between 2000 and May 2010.

Dr. Kim and his associates in the RACER study group identified 59 marathon-related cardiac arrests (out of 10.9 million registered marathon runners) during this period and contacted survivors, as well as the next of kin of nonsurvivors, to ascertain demographic data, exercise history, personal and family medical histories, and pertinent medical records.

The overall incidence of cardiac arrest was 1 per 184,000 participants, and that of sudden death was 1 per 259,000 participants. This translates to 0.2 cardiac arrests and 0.14 sudden deaths per 100,000 runner-hours at risk, assuming an average running time of 4 hours for marathons and 2 hours for half-marathons.

“Thus, event rates among marathon and half-marathon runners are relatively low, as compared with other athletic populations, including collegiate athletes (1 death per 43,770 participants per year), triathlon participants (1 death per 52,630 participants), and previously healthy middle-aged joggers (1 death per 7,620 participants),” the researchers wrote (N. Engl. J. Med. 2012;366:130-40).

The absolute number of marathon-related cardiac arrests rose each year during the study period, but the incidence remained stable because of an annual increase in runners from fewer than 1 million in 2000 to approximately 2 million in 2010, according to the investigators.

Men were more likely than were women runners to have a cardiac arrest or sudden death (0.90 per 100,000 vs. 0.16 per 100,000), which the authors noted is “consistent with reports on other populations and reaffirms a male predisposition to exertional cardiac arrest.”

The distance of a race was a key determinant of the risk of cardiac arrest, since rates were three to five times higher during marathons (1.01 per 100,000 runners) than during half-marathons (0.27 per 100,000). “A possible explanation is that longer races involve more physiological stress and thus a higher likelihood of precipitating an adverse event in a predisposed participant,” the researchers wrote.

The overall case fatality rate was 71%. Sufficient information was available to determine the cause of cardiac arrest in only 31 of the 59 cases.

The most frequent cause of death was hypertrophic cardiomyopathy (8 cases) or possible hypertrophic cardiomyopathy (7 cases). This is also the primary cause of death in young competitive athletes, they pointed out.

“Notably, 9 of the 15 nonsurvivors who had cardiac hypertrophy had an additional clinical factor or postmortem finding: obstructive coronary artery disease (in 3), myocarditis (in 2), bicuspid aortic valve or coronary anomaly (in 2), accessory atrioventricular nodal bypass tract (in 1), or hyperthermia (in 1),” the researchers wrote. The race-related disorders of hyperthermia and hyponatremia, which led to the death of one runner without cardiac hypertrophy, thus are not common causes of cardiac arrest and sudden death, they added.

Among the eight survivors of cardiac arrest, ischemic heart disease was the most frequent cause of the arrest. The strongest predictor of survival of cardiac arrest was bystander-administered CPR, underscoring the importance of onsite medical services.

It was “surprising” that none of the runners with serious coronary atherosclerosis had angiographic evidence of acute plaque rupture or thrombus, because previous studies as well as expert consensus statements have suggest that exercise-induced coronary syndromes result from disruption of atherosclerotic plaque and coronary thrombosis. “In contrast, our findings suggest that demand ischemia (i.e., ischemia due to an imbalance between oxygen supply and demand) may be operative in exercise-related acute coronary events during long-distance running races,” they wrote.

This finding also suggests that the practice of taking aspirin before a race to prevent cardiac arrest is likely ineffective, since acute coronary artery thrombosis is not an important cause of marathon-related cardiac arrest, they added.

Physicians called on to evaluate potential marathon participants “should be aware of the risks of hypertrophic cardiomyopathy and atherosclerotic disease in this patient population.” Prerace exercise testing may detect physiologically significant coronary artery stenosis or may identify patients with exertion-induced myocardial ischemia, the investigators said.

This study was limited in that the researchers were unable to obtain complete clinical information on 45% of the nonsurvivors or on 53% of the survivors.

Dr. Kim reported no financial conflicts of interest, but two of his coauthors reported ties to industry sources.

Subject Codes:
top_stories; sports; general_primary; cardiology;

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January 11, 2012 05:00 PM EST

While it may appear that cardiac arrests related to marathon running have increased, researchers say it’s because more people are participating in the sport. The incidence of cardiac arrests remained stable over the study period.

ASSERT: Subclinical Atrial Fib Boosts Stroke Risk

Wed, 11 Jan 2012 22:00 GMT

BY BRUCE JANCIN
Elsevier Global Medical News
Breaking News

Asymptomatic episodes of atrial fibrillation are common in elderly hypertensive patients with pacemakers and no history of clinical AF – and these subclinical atrial tachyarrhythmias are associated with a sharply increased risk of subsequent ischemic stroke.

These were the two major findings of the large, international, randomized ASSERT (Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial) study.

An important secondary finding was that, disappointingly, continuous atrial overdrive pacing using a programmable algorithm to maintain a paced atrium did not prevent the development of clinical AF, nor did it modify stroke risk, according to Dr. Jeff S. Healey of the Population Health Research Institute at McMaster University in Hamilton, Ont.

ASSERT enrolled 2,580 patients in 23 countries. All were aged 65 years or older, were hypertensive, and had recently received a dual-chamber pacemaker or implantable cardioverter-defibrillator. None of the subjects had a history of AF at enrollment.

In the first 3 months of follow-up, 10.1% of study participants developed device-detected subclinical AF (defined as an atrial rate in excess of 190 beats per minute lasting for more than 6 minutes). As a practical matter, it’s worth noting that the median time to implanted device–detected asymptomatic AF in this subgroup was 36 days. Thus, several days of negative Holter monitoring would have made for false reassurance, the cardiologist noted.

The subgroup with asymptomatic AF during the first 3 months had a 5.6-fold increased risk of developing clinical AF during a mean 2.5 years of prospective follow-up. Moreover, the rate of ischemic stroke or systemic embolism in patients with subclinical AF in the first 3 months was 1.7% per year, compared with 0.69% annually in the rest of the ASSERT participants.

The population attributable risk (PAR) of stroke or systemic embolism associated with asymptomatic AF in the first 3 months was 13%. Of note, that’s similar to the PAR of stroke that is associated with clinical AF in the Framingham Heart Study.

In a multivariate analysis adjusted for the standard predictors of stroke, device-detected subclinical AF during the first 3 months of the study was independently associated with a 2.5-fold increased subsequent risk of stroke. And this may well underestimate the true magnitude of risk, since more than half of ASSERT participants were on aspirin at baseline and 18% of those with early subclinical AF received warfarin during the follow-up period.

Both of these venerable drugs are clearly effective in reducing stroke risk in patients with established clinical AF, although it’s not known whether these agents also have a net benefit in patients with subclinical AF. A randomized trial testing this hypothesis by using these drugs or newer anticoagulants should be a priority, Dr. Healey said (N. Engl. J. Med. 2012;366:120-9).

Subjects with a CHADS2 score greater than 2 plus subclinical AF detected in the first 3 months of the study had a rate of ischemic stroke or systemic embolism of 3.7% per year, compared with 0.97% per year in patients with a similarly elevated CHADS2 score but no early subclinical atrial tachyarrhythmia.

In addition to the 10% of ASSERT participants who developed subclinical AF during the initial 3 months of follow-up, another 24% did so later.

Episodes of asymptomatic AF briefer than 6 minutes were not catalogued in the study, so it remains unknown if they, too, are associated with increased subsequent stroke risk.

At the study’s outset, all subjects with pacemakers were randomized to continuous atrial overdrive pacing or to having this feature switched off for the duration. The atrial pacing intervention did not affect the rate of development of clinical AF, although the trial was underpowered for this outcome.

How Much Atrial Arrhythmia Is Too Much?

In an editorial accompanying the study, Dr. Gervasio Lamas noted that although this “robust” study convincingly demonstrates that device-detected subclinical AF was independently associated with a more-than-doubled annualized risk of stroke or peripheral embolism, the question of cause vs. effect remains open: Are these asymptomatic episodes of AF actually causing cardioembolic stroke, or are they merely a marker of stroke risk, possibly reflecting myocardial fibrosis or structural heart disease (N. Engl. J. Med. 2012;366:178-80)?

It’s noteworthy that the lengthier the longest episode of subclinical AF in the first 3 months of the ASSERT study, the greater the subsequent stroke risk, said Dr. Lamas, chairman of medicine at Mount Sinai Medical Center in Miami Beach. Among those whose longest episode lasted more than 17.7 hours, the risk of stroke or systemic embolism was increased nearly fivefold.

The ASSERT investigators have identified a large and interesting population at increased risk of stroke, he noted. But “until definitive, randomized clinical trials have been carried out demonstrating that anticoagulant therapy is justified for patients with short episodes of device-detected AF, I’m going to continue relying upon the CHADS2 score for guidance in deciding upon whether to prescribe a prophylactic anticoagulant. I’ll consider applying the CHADS2 metric to patients with subclinical episodes of AF lasting for hours.”

The ASSERT study was supported by St. Jude Medical. Dr. Healey disclosed that he has served as a paid consultant to that company, Boehringer Ingelheim, and Bayer, as well receiving grant support from AstraZeneca, Boston Scientific, and Boehringer Ingelheim. Dr. Lamas declared having no relevant financial interests.

Subject Codes:
top_stories; cardiology; neurology;

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January 11, 2012 05:00 PM EST

Dr. Jeff S. Healey

New Stroke-Prevention Drugs Spur A-Fib Guides

Wed, 11 Jan 2012 07:48 GMT

BY HEIDI SPLETE
Elsevier Global Medical News
Breaking News

WASHINGTON (EGMN) –The American College of Physicians has created pharmaceutical company–sponsored physician and patient education materials aimed at preventing strokes among the estimated 2.6 million Americans with atrial fibrillation.

Providers who manage patients with atrial fibrillation have tended to underestimate the risk of stroke and overestimate the risk of bleeding from anticoagulants, which has contributed the undertreatment of patients who could benefit from anticoagulation therapy, according to Dr. Samuel Z. Goldhaber. The side effects associated with warfarin made it an unappealing choice. But new oral medications, such as dabigatran, are providing more options, said the cardiologist at Harvard University and Brigham and Women’s Hospital in Boston.

The effort, spearheaded by the ACP’s Initiative on Atrial Fibrillation and Stroke Prevention, shores up the role of primary care in atrial fibrillation management at a time when newly approved alternatives to warfarin have dramatically expanded treatment options. “You don’t need to be a specialist to prevent a stroke from atrial fibrillation,” said Dr. Goldhaber, a member the initiative’s panel.

The materials are aimed at helping the internal medicine physician, family physician, or nurse practitioner play a role in preventing stroke by looking for atrial fibrillation, and, when appropriate, selecting a treatment agent, which in the future is more likely to be an oral anticoagulant, he said at a Jan. 10 press conference.

Janssen Pharmaceuticals, manufacturer of rivaroxaban, sponsored the development of the concise, one-page clinician work sheet that can be used at the bedside, a patient and caregiver booklet, and three patient videos to help patients understand whether they are candidates for anticoagulation medication.

In addition, the initiative produced a compendium addressing quality of care issues at the hospital level for the purposes of educating staff about atrial fibrillation management.

In evaluating whether patients are candidates for anticoagulation therapy, the clinician tool advises the use the CHADS2scoring system to assess stroke risk, the outpatient bleeding risk index (OBRI), and doing an assessment of the individual’s risk for falling.

The patient booklet, in large print, features tips from atrial fibrillation patients.

The videos feature a physician’s explanation of anticoagulation therapy, including a discussion of treatment options with an actual patient

When patients are more empowered and educated, they are more likely to adhere to any decisions they make with their clinicians, said Dr. Barbara Schuster of Georgia Health Sciences University in Augusta, and cochair of the ACP’s initiative panel.

“It is the conversation between the patient and clinician that helps them take hold of their own health care,” she said.

But the tools aren’t only about medication, Dr. Goldhaber noted. As patients review the materials, they will get an overview of stroke risk, which is designed to reinforce the importance of heart-healthy living; maintaining a healthy blood pressure, taking antihypertensive medications, and eating sensibly, he said.

The new materials are expected to be available at the ACP website, and they are scheduled to be presented and distributed at the ACP annual meeting this spring.

Dr. Goldhaber has received research support from Bristol-Myers Squibb, Boehringer Ingelheim, Eisai, EKOS, Johnson & Johnson, and Sanofi-Aventis. He has served as a consultant to Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi, Eisai, Merck, Pfizer, Portola, and Sanofi-Aventis.

Click here to view a video related to this presentation.

Subject Codes:
general_primary; cardiology;

http://www.imng.com

January 11, 2012 02:48 AM EST

Samuel Z. Goldhaber

Potassium Targets for Acute MI Too High, Outdated

Tue, 10 Jan 2012 21:00 GMT

BY MARY ANN MOON
Elsevier Global Medical News
Breaking News

Current guidelines for correcting serum potassium levels in patients who present with acute MI are out of date and aim for targets that are too high, raising the risk of in-hospital mortality, according to a report in the Jan. 11 issue of JAMA.

In a retrospective study of 38,689 cases of MI in a nationally representative database, there was a U-shaped relationship between serum potassium level at admission an in-hospital mortality. The lowest mortality occurred in patients with potassium levels of 3.5-4.5 mEq/L, with higher mortality in those with potassium levels of 4.5 mEq/L or higher as well as those with levels less than 3.5 mEq/L.

Current practice guidelines recommend raising “low” potassium to 4.0-5.0 mEq/L, “and some experts even advise a higher range of 4.5-5.5 mEq/L,” said Dr. Abhinav Goyal of the schools of medicine and public health at Emory University, Atlanta, and his associates.

“These guidelines are based on small, older studies that focused only on [preventing] ventricular arrhythmias (and not mortality) and were conducted before the routine use of beta-blockers, reperfusion therapy, and early invasive management in acute MI patients. Our data suggest that ... potassium levels of greater than 4.5 mEq/L are associated with increased mortality and probably should be avoided,” they noted.

Dr. Goyal and his colleagues performed their study because measuring and repleting potassium to prevent arrhythmia in patients who present with acute MI is an entrenched practice, despite “the lack of current, adequately powered studies that define the optimal range of serum potassium levels with respect to mortality and other important clinical outcomes.” They used information from the Cerner Corporation’s Health Facts database, which covers nearly 400,000 consecutive MI patients who presented to 67 U.S. hospitals representing all geographic regions of the country in 2000-2008.

A total of 2,679 of these study subjects (6.9%) died during hospitalization.

Compared with the reference group (potassium level of 3.5-4.0 mEq/L), in which in-hospital mortality was 4.8%, patients with levels of 4.0-4.5 had comparable mortality (5.0%).

In contrast, mortality was twice as great (10.0%) for patients with potassium levels of 4.5-5.0 mEq/L, and was even greater at higher levels, the investigators said (JAMA 2012;307:157-64).

“Our findings suggest that overly aggressive repletion of potassium levels (which is often automated through the implementation of hospital order sets) may not be advisable in patients with acute MI ... as potassium levels of at least 4.5 mEq/L are associated with harm,” they noted.

As expected, mortality also was greater for patients with low potassium levels below 3.5 mEq/L.

These associations persisted in further analyses that adjusted for potentially confounding factors such as patient age, sex, and glomerular filtration rate at admission. They also remained robust regardless of whether patients did or did not receive potassium supplementation during hospitalization, and remained robust when the analysis was restricted only to patients who survived past the first 24 hours.

The investigators cautioned that their findings apply only to patients with acute MI and should not be extrapolated to those with other cardiac conditions, including heart failure.

This study was supported in part by Saint Luke’s Mid America Heart Institute, Kansas City, Mo. No conflicts of interest were reported.

Higher Potassium Targets ‘Not Justified’

Potassium repletion to levels higher than 4.5 mEq/L no longer appear to be justified in acute MI, said Dr. Benjamin M. Scirica and Dr. David A. Morrow.

Even potassium levels of 4.0-4.5 mEq/L were associated with increased mortality, compared with levels of 3.5-4.0 mEq/L, and 43% of all the patients in this study fell into that category.

However, it is reasonable to avoid significant hypokalemia (less than 3.5 mEq/L), especially for patients who have significant, sustained, ventricular ectopy or other high-risk features.

Dr. Scirica and Dr. Morrow are at the Levine Cardiac Unit at Brigham and Women’s Hospital and Harvard Medical School, both in Boston. They reported numerous ties to pharmaceutical companies. These remarks were adapted from their editorial comment accompanying Dr. Goyal’s report (JAMA 2012;307:195-6).

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top_stories; cardiology;

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January 10, 2012 04:00 PM EST

Dabigatran Tied to Increase in Heart Attack Risk

Mon, 09 Jan 2012 21:00 GMT

BY MARY ANN MOON
Elsevier Global Medical News
Breaking News

The direct thrombin inhibitor dabigatran appears to raise the risk of myocardial infarction or acute coronary syndromes, according to a meta-analysis of seven randomized clinical trials published online Jan. 9 in the Archives of Internal Medicine.

The meta-analysis included randomized clinical trials assessing the noninferiority of dabigatran against various control treatments including adjusted-dose warfarin, enoxaparin, and placebo, in a broad spectrum of patients using the drug for a variety of indications.

“We used several meta-analytic methods and several association measures, and the results were consistent. Although the relative risk increase was 33%, the absolute risk increase was very small, at 0.27%,” said Dr. Ken Uchino and Dr. Adrian V. Hernandez, both of the Cleveland Clinic.

The mechanism by which dabigatran increases the risk of MI or acute coronary syndrome (ACS) is not yet known. It is possible that the drug doesn’t actively raise this risk, but instead lacks some protective effect that the control treatments possess, the investigators noted.

The meta-analysis covered 30,514 study subjects, including patients with atrial fibrillation who used dabigatran to prevent stroke, patients with atrial fibrillation who used it to prevent acute venous thromboembolism, patients with ACS who used it to prevent recurrent ACS, and patients undergoing joint replacement who used it to prevent deep vein thrombosis.

Overall, patients who received dabigatran were at significantly higher risk of MI or ACS than were control patients. The incidence of these events was 1.19% in those taking dabigatran, compared with 0.79% in control subjects, Dr. Uchino and Dr. Hernandez said (Arch. Intern. Med. 2012 [doi:10.1001/archinternmed.2011.1666]).

Since it is possible that dabigatran’s negative effects may increase with longer duration of use, the investigators performed a separate analysis excluding three of the seven studies that had exceptionally short (less than 1 month) exposure times. The risk of MI or ACS remained high and significant in this analysis of the data, they noted.

An important limitation of the meta-analysis is that a single large trial, with a study population of 18,113 patients, overshadowed the findings from the other 6 trials, which had populations of 515 to 2,451 patients. In addition, the large trial followed patients for a median of 2 years, while the smaller trials did so for 6 months or less.

Because of this imbalance, the large trial accounted for 59% of the meta-analysis cohort and 74% of the cardiovascular events, they said.

Overall, the findings indicate that dabigatran’s cardiovascular risks should be investigated further, “especially if [the drug] is used in populations at high risk of MI or ACS,” they added.

The “robust” finding by Dr. Uchino and Dr. Hernandez that dabigatran is associated with increased MI “is alarming and emphasizes the need for continued critical appraisal of new drugs after phase III trials,” Dr. Jeremy M. Jacobs and Dr. Jochanan Stessman wrote in remarks taken from an invited commentary that accompanied the meta-analysis (Arch. Intern. Med. 2012 [doi:10.1001/archinternmed.2011.1721]).

The researchers’ results “suggest that physicians [should] step back for a moment, take their own pulse, and retain a critical view as a powerful new drug enters clinical use on a potentially massive scale,” Dr. Jacobs of the Jerusalem Institute of Aging Research at Hadassah-Hebrew University Medical Center and Dr. Stessman of the Hebrew University–Hadassah Medical School, Jerusalem.

The findings also highlight another deeply concerning issue: “the enthusiasm – nearly to the level of euphoria – to embrace the new,” they added.

All seven studies included in the meta-analysis were sponsored by the drug manufacturer, Boehringer Ingelheim. No financial conflicts of interest were reported among the investigators for this current study.

Dr. Jacobs and Dr. Stessman reported having no financial conflicts of interest.

Subject Codes:
top_stories; cardiology; surgery; neurology;

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January 09, 2012 04:00 PM EST

New Drug-Eluting Stents Far Safer Than Older Models

Mon, 09 Jan 2012 08:05 GMT

BY SHARON WORCESTER
Elsevier Global Medical News
Breaking News

Percutaneous coronary intervention with new-generation drug-eluting stents is associated with significantly lower risk of restenosis, stent thrombosis, and death, compared with both older generation drug-eluting stents and bare-metal stents, according to findings from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR).

The findings bolster the current recommendations regarding use of drug-eluting stents (DES), and are the first to show a mortality benefit with new- vs. older-generation DES. Compared with older bare-metal stents (BMS), the risk of death was reduced with older DES at 2 years, by 28%, and lower still with new DES, by 45%.

The 1- and 2-year restenosis rates among 10,551 implantations with a new-generation DES in SCAAR were 2.8% and 3.9%, respectively, compared with 4.0% and 5.8% in 19,202 implantations with an older-generation DES (cumulative adjusted hazard ratio, 0.62), and 6.3% and 7.4% in 64,631 implantations with a BMS (cumulative adjusted HR, 0.29), wrote Dr. Giovanna Sarno of Uppsala (Sweden) University and colleagues. The results are online in the Jan. 9 issue of the European Heart Journal.

The 1- and 2-year definite stent thrombosis rates among the new-generation DES implantations were 0.5% and 0.6%, respectively, compared with 0.9% and 1.3% in the older-generation DES implantations, for a risk reduction of 43%, and 1.2% and 1.4% in the bare-metal stent implantations, showing a 62% reduction in risk.

The overall mortality rate among the 61,351 patients who underwent the 94,384 stent implantations was 5.6%. Mortality was 1.9% in the new-generation DES recipients, compared with 3.4% in the older-generation DES recipients (adjusted hazard ratio, 0.77), and 6.8% in the bare-metal stent recipients (adjusted HR 0.55), the investigators said (Eur. Heart J. 2011 Jan. 9 [doi:10.1093/eurheartj/ehr479]).

“A main finding of this study is that new-generation DES are associated with a 38% lower risk of clinically relevant restenosis and a 43% lower risk of definite stent thrombosis up to 2 years, compared with older-generation DES in a large real world population,” the investigators said.

Furthermore, the findings indicate that mortality with new-generation and older-generation DES is 45% and 28% lower, respectively, than with bare-metal stents, and 23% lower with new-generation DES than with older-generation DES, they said.

New-generation DES were developed with an improved design, including thinner struts and more biocompatible polymers, thought to have potential for overcoming limitations – namely those relating to long-term safety, and particularly risk of late stent thrombosis – of older generation DES. Although randomized studies demonstrated low late loss and thrombotic risk with restricted use of the new generation DES, only a few trials and reports from single-center experiences evaluating only one type of the new generation DES have looked at unrestricted use.

“Our study evaluated the performance up to 2 years of different types of new-generation DES in an unselected large real-world population – including patients with myocardial infarction, three-vessel and/or left main disease, bifurcation lesions, graft disease, restenotic lesions, and chronic total occlusions,” the investigators said.

Participants in the observational cohort study included all patients in Sweden who received coronary stents from November 2006 to October 2010. In their analysis, the investigators adjusted for potential confounders, including age, sex, diabetes, hypertension, dyslipidemia, smoking status, clinical indication of the procedure, medications used at the index procedure, treated vessel and lesion type, and previous MI and revascularization.

In a press statement, study author Dr. Stefan James, also of Uppsala University, described the findings as “intriguing” and noted that, “the low rates of restenosis and stent thrombosis correspond with the results of several recent randomized trials, and this may well translate into mortality reduction in a sufficiently large study population.”

However, despite the large sample size, the findings of this study should be considered within the context of the intrinsic limitations of registry data. Although the findings may be useful for the management of patients at risk for stent thrombosis and restenosis – and although they support the current strong recommendations for the use of drug-eluting stents in appropriate patients, they require confirmation by large-scale randomized studies, the investigators concluded.

New-generation DES used in this study included Endeavor Resolute (Medtronic Inc.), XienceV, Xience Prime (Abbott Laboratories), and Promus and Promus Element (Boston Scientific Corp.). Older generation DES included Cypher and Cypher Select (Cordis Corp., Miami), Taxus Express and Taxus Liberté (Boston Scientific Corp.), and Endeavor (Medtronic Inc.) Bare-metal stents include Multilink, Multilink MiniVision, and Flexmaster (Abbott Laboratories), Driver and Micro Driver coronary (Medtronic Inc.), Liberté (Boston Scientific Corp.), Braun Coroflex Blue (B.Braun Melsungen AG, Germany), and Chrono stent (CID, Saluggia, Italy).

SCAAR is sponsored by the Swedish Health Authorities. Financial support for analyses was provided by the Swedish Heart and Lung Foundation. One study author, Dr. James, disclosed that he received institutional research grants from Terumo, Medtronic, and Vascular Solutions.

Subject Codes:
top_stories; cardiology;

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January 09, 2012 03:05 AM EST