ANTICOAGULATION FOR DVT IN CALF MAY REDUCE CLOT PROPAGATION RISK

MedPage Today (6/18, Phend) reported, "Anticoagulation for deep vein thrombosis (DVT) in the calf reduces risk that the clot will propagate and may improve other clinical outcomes as well," according to the research presented at the Society for Vascular Surgery's Vascular annual meeting in Illinois. Among the more than 2,300 studies Randall R. De Martino, MD, of Dartmouth-Hitchcock Medical Center in Lebanon, N.H., and colleagues, "pooled the results of eight studies in adults with ultrasound- or venogram-confirmed calf DVT who were followed for at least one month after treatment with an anticoagulant for at least 30 days or no anticoagulation" and found that "patients who received vitamin K antagonists or heparin had dramatically lower rates of pulmonary embolism and clot propagation compared with those who went without anticoagulants."

POSTED BY STEVEN ALMANY, MD

FDA SAYS CHANTIX MAY SLIGHTLY INCREASE RISK OF HEART ATTACK

The AP (6/17, Perrone) reports, "Federal health regulators are warning doctors and patients that Pfizer's anti-smoking drug Chantix [varenicline] may slightly increase the risk of heart attack and other cardiovascular problems." On Thursday, the FDA "said...a study of 700-heart disease patients taking Chantix showed a small uptick in heart problems among those taking the smoking-cessation drug versus those taking placebo." The agency "will add new warnings to the drug's label about the study's findings."

Bloomberg News (6/17, Larkin, Edney) reports that the agency will also require "Pfizer...to further evaluate the heart risks with an analysis of existing studies."

Reuters (6/17) reports that in a statement, the agency said, "The known benefits of Chantix should be weighed against its potential risks when deciding to use the drug in smokers with cardiovascular disease."

The Los Angeles Times (6/16, Cevallos) "Booster Shots" blog pointed out that "heart problems aren't the only warning associated with Chantix. In 2009 the FDA warned that the drug might increase the risk of suicidal thoughts and behaviors." Also covering the story were Dow Jones Newswire (6/17, Dooren, Subscription Publication), AFP (6/17), HeartWire (6/16, O'Riordan), MedPage Today (6/16, Peck), HealthDay (6/16), and WebMD (6/16, Mann).

POSTED BY STEVEN ALMANY, MD

FDA IS RECOMMENDING PHYSICIANS RESTRICT PRESCRIBING HIGH-DOSE SIMVASTATIN (ZOCOR, MERCK) TO PATIENTS, GIVEN INCREASED RISK OF MUSCLE DAMAGE

June 8, 2011 (Silver Spring, Maryland) — The Food and Drug Administration is recommending that physicians restrict prescribing high-dose simvastatin (Zocor, Merck) to patients, given an increased risk of muscle damage [1]. The new FDA drug safety communication, issued today, states that physicians should limit using the 80-mg dose unless the patient has already been taking the drug for 12 months and there is no evidence of myopathy.

"Simvastatin 80 mg should not be started in new patients, including patients already taking lower doses of the drug," the agency states.

In addition, the FDA is requesting that additional changes be made to the drug's label. The label will be changed to include the new dosing recommendations, as well as warnings not to use the drug with various medications, including itraconazole (Sporanox, Jannsen Pharmaceutica), ketoconazole (Nizoral by Ortho-McNeil Pharmaceutical), posaconazole (Noxafil, Merck), erythromycin, clarithromycin, telithromycin (Ketek, Sanofi-Aventis), HIV protease inhibitors, nefazodone, gemfibrozil, cyclosporine, and danazol.

In addition, the 10-mg dose should not be exceeded in patients taking amiodarone, verapamil, and diltiazem, and the 20-mg dose should not be exceeded with amlodipine (Norvasc, Pfizer) and ranolazine (Ranexa, Gilead).

The changes to the label are based on the Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH), a study reported by heartwire . In that trial, 52 patients taking the 80-mg dose developed myopathy compared with one patient treated with the 20-mg dose. In addition, 22 patients treated with the high dose of simvastatin developed rhabdomyolysis compared with none treated with the 20-mg dose.

The FDA notes that the risks of myopathy and rhabdomyolysis were highest in the first year and that older age and female sex increased the risks.

In statement released today following the FDA alert [2], Merck notes that it has launched a new information website and is encouraging patients who think the prescribing changes might affect them to speak with their doctors.

POSTED BY STEVEN ALMANY, MD

REMOVING TONSILS, APPENDIX MAY BE LINKED TO INCREASED RISK OF EARLY HEART ATTACK

HealthDay (6/1, Dallas) reported that "although the tonsils and appendix are not considered vital to the body, Swedish researchers have found that people who had them taken out before the age of 20 may be at a slightly greater risk of an early heart attack." Investigators "identified 54,449 appendectomies and 27,284 tonsillectomies performed on Swedish residents under the age of 20 years." The participants were followed for an average of more than 23 years. The researchers "concluded that tonsillectomy increased the relative risk of a heart attack by 44 percent, and appendectomy increased the relative risk by 33 percent." The study was published online in the European Heart Journal.

POSTED BY STEVEN ALMANY, MD

SCREENING COLLEGE ATHLETES MAY HELP PREVENT INCIDENTS OF SUDDEN CARDIAC DEATH

HealthDay (6/1, Dallas) reported that "screening college athletes for heart conditions before they participate in sports could help prevent incidents of sudden cardiac death, according to a new study" published in The American Journal of Medicine. In the study, "nearly one in four athletes tested either had a distinct heart abnormality or symptoms that required further screening." The authors of the study "noted that American Heart Association/American College of Cardiology guidelines for pre-participation screening effectively identified nearly 25 percent of athletes who were candidates for heart screening based on history or symptoms

POSTED BY STEVEN ALMANY, MD

NEARLY 20% OF YOUNG ADULTS IN US MAY HAVE HIGH BLOOD PRESSURE

ABC World News (5/25, story 6, 0:25, Sawyer) reported that research published online in Epidemiology indicates that nearly one-fifth "of Americans who are 24 to 32 years old have high blood pressure."

USA Today (5/26, Marcus) reports, "For the National Longitudinal Study of Adolescent Health, dubbed Add Health, funded by the National Institutes of Health, researchers from the University of North Carolina-Chapel Hill asked 14,000 men and women between the ages of 24 and 32 about their high blood pressure history and then took blood pressure readings of participants." The investigators "found that 19% of participants had high blood pressure." These "findings...are significantly higher than other recent research from another large, ongoing health study, the National Health and Nutrition Examination Survey (NHANES), which found only 4% of adults 20 to 39 have high blood pressure."

The CNN (5/25) "The Chart" blog reported that lead study author Kathleen Mullan Harris said that "among those measured with high blood pressure, only 25% had been told previously that they had high blood pressure." Also covering the story were the Raleigh News & Observer (5/26, Price), Reuters (5/26, Steenhuysen), WebMD (5/25, Mann), HealthDay (5/25, Dallas), and MedPage Today (5/25, Neale).

POSTED BY STEVEN ALMANY, MD

TRIAL OF EXTENDED-RELEASE NIACIN (NIASPAN, ABBOTT) HALTED PREMATURELY

May 26, 2011 (Bethesda, Maryland) — A trial of extended-release niacin (Niaspan, Abbott) given in addition to statin therapy in patients with a history of cardiovascular disease, high triglycerides, and low levels of HDL cholesterol has been halted prematurely, 18 months ahead of schedule, because niacin offered no additional benefits in this patient population [1].

There was also a small, unexplained increase in ischemic stroke in the high-dose, extended-release niacin group, in the Atherothrombosis Intervention in Metabolic Syndrome with Low HDL Cholesterol/High Triglyceride and Impact on Global Health Outcomes (AIM-HIGH) study, according to a statement from the National Heart Lung and Blood Institute (NHLBI), which sponsored it.

Despite treatment with statin therapy for elevated LDL-cholesterol levels, those with low levels of HDL cholesterol remain at significant risk for cardiovascular events, and AIM-HIGH was designed to examine whether raising HDL using extended-release niacin would be beneficial in such patients. AIM-HIGH was a five-year study of almost 3500 patients, and results were originally expected in September 2012.
The decision to stop the trial was made at a regularly scheduled meeting of the study's independent data and safety monitoring board (DSMB) on April 25, 2011. The DSMB concluded that "high-dose, extended-release niacin offered no benefits beyond statin therapy alone in reducing cardiovascular-related complications in this trial. The rate of clinical events was the same in both treatment groups, and there was no evidence that this would change by continuing the trial."

Patients Should Not Stop Taking Niacin
The NHLBI explains that the rationale for AIM-HIGH was based on data from observational studies and a few small clinical studies. "This study sought to confirm earlier and smaller studies," says Dr Susan B Shurin (acting director of the NHLBI) in the statement. "Although we did not see the expected clinical benefit, we have answered an important scientific question about treatment for cardiovascular disease.”

Several other trials testing this hypothesis, including a large international trial of high-dose, extended-release niacin, the Heart Protection Study 2 Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE), are still under way; results of HPS2-THRIVE are expected in 2013. Extended-release formulations of niacin are being used in these trials because the immediate-release form of niacin is associated with a high incidence of flushing.

Previous studies do not suggest that stroke is a potential complication of niacin, and it remains unclear whether this trend in AIM-HIGH arose by chance or was related to niacin administration or some other issue, says the NHLBI. "Patients who were not in the AIM-HIGH trial should not stop taking high-dose, extended-release niacin without talking to their doctor first," says Shurin.

All AIM-HIGH study participants have been informed of the results and will be scheduled for clinic visits within the next 2.5 months. Participants will be followed for an additional 12 to 18 months.

AIM-HIGH co–principal investigator Dr Jeffrey Probstfield (University of Washington, Seattle) said: "The lack of effect on cardiovascular events is unexpected and a striking contrast to the results of previous trials and observational studies. The AIM-HIGH findings do not support the trial’s hypothesis that, in the population studied, adding extended-release niacin to simvastatin in participants with well-controlled LDL cholesterol can provide additional clinical benefit.”
AIM-HIGH enrolled 3414 participants in the US and Canada with a history of cardiovascular disease, low HDL cholesterol, and high triglycerides, who were all prescribed simvastatin and who were also randomized to either high-dose, extended-release niacin in gradually increasing doses up to 2000 mg per day (n=1718) or placebo (n=1696). Of the participants, 515 were given a second LDL-cholesterol–lowering drug, ezetimibe (Zetia, Merck/Schering-Plough), in order to maintain LDL-cholesterol levels at the target range between 40 and 80 mg/dL.

Participants who took high-dose, extended-release niacin and statin treatment had increased HDL cholesterol and lowered triglyceride levels than participants who took a statin alone. However, the combination treatment did not reduce fatal or nonfatal MI, strokes, hospitalizations for acute coronary syndrome, or revascularization procedures.

During the 32-month follow-up period, there were 28 strokes (1.6%) reported among participants taking high-dose, extended-release niacin vs 12 strokes (0.7%) in the control group. Nine of the 28 strokes in the niacin group occurred in participants who had discontinued the drug at least two months and up to four years before their stroke.