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By William T. Elliott, MD, FACP
Bayer has withdrawn cerivastatin (baycol) from the worldwide market after as many as 52 deaths have been attributed to the drug. The deaths were caused by rhabdomyolysis. Most of the deaths were in older patients on high doses of the drug, and many of these patients were also taking gemfibrozil, a drug known to increase the risk of myositis with all statins. While statins are known to cause myositis in a small minority of patients, the rate and the severity of the disorder with cerivastatin was excessive, accounting for more than half of the cases of rhabdomyolysis reported for all statins. The effect of the withdrawal has been disastrous for Bayer, and may force the company to sell its pharmaceutical unit or partner with another company. Meanwhile, manufacturers of other statins are relooking at their own data, and reissuing warnings about the use of statins with gemfibrozil. The FDA is also dealing with a petition from the watchdog group Public Citizen to put "Black Box" warnings on all statins, concerning the risk of rhabdomyolysis. But a disaster for one company is a marketing opportunity for another, so statin manufacturers are aggressively stepping into the lost cerivastatin market with offers of free drugs and other enticements to patients willing to switch.
Do COX-2 inhibitors promote cardiovascular events? A recent meta-analysis from the Cleveland Clinic tries to answer this question. The theory that COX-2s may lead to prothrombotic activity by decreasing vasodilatory and antiaggregatory prostacyclin production is the source of this concern. The study looked at the VIGOR trial that compared rofecoxib with naproxen, the CLASS trial comparing celecoxib with ibuprofen, and 2 smaller studies of the COX-2 drugs. While the VIGOR trial showed an increase in cardiovascular events with rofecoxib, the CLASS trial did not. However, when the CLASS data, and data from the smaller COX-2 studies were combined and compared to rates of cardiovascular events from other studies, the rates of cardiovascular events were higher than expected in users of COX-2 inhibitors. Mukherjee and colleagues admit that this study is far from conclusive, but it does raise a "cautionary flag" about the risk of cardiovascular events associated with the use of COX-2 inhibitors (Mukherjee D, et al. JAMA. 2001;286:954-959).
Oxycontin has become a favorite drug of abuse, especially in rural America. Now Purdue Pharma, the manufacturer of the drug, is working to prevent street use of the drug in a rather ingenious fashion. The time-released drug is crushed by abusers, defeating the time-release properties. After crushing, the powder is then injected or snorted. The company is working on combining an opiate antagonist with oxycodone. The antagonist would be inert when taken orally, but would be activated if the capsule is crushed, potentially triggering opiate withdrawal symptoms in abusers. Purdue Pharma is applying for an international patent for this new formulation.
Drugs are ineffective for preventing ventricular tachycardia (VT) according to the Multicenter UnSustained Tachycardia Trial (MUSTT) trial. More than 700 patients with a history nonsustained VT were randomized to PVS-guided antiarrhythmic therapy or no drug therapy. There was no benefit found to drug therapy despite looking at several different end points. Several antiarrhythmic drugs were evaluated, but none was found to be superior to the others. The one positive outcome was seen with PVS-guided implantable defibrillators, which were found to significantly improve outcomes (Wyse D, et al. J Am Coll Cardiol. 2001;38:344-351).
The FDA has approved a new treatment for hepatitis C. Schering’s peginterferon alfa-2b (Peg-Intron) has been approved for use with ribavirin (Rebetol) for patients with chronic hepatitis C with compensated liver disease who have not previously been treated with interferon. Pegelated interferon was developed using a polyethylene glycol molecule (PEG) and combining it with interferon to form an injectable form that can be given once a week instead of 3 times a week as was the case with interferon alpha-2b (Intron-A). Ribavirin, which is also a Schering product, was previously approved for use with Intron-A. Along with being more convenient, peginterferon/ribavirin is more effective than interferon/ribavirin in treating chronic hepatitis C according to documentation filed with the FDA. Hoffman-LaRoche has developed their own pegelated interferon product, peginterferon alpha-2a (Pegasys). The 2 companies recently reached a long-term co-marketing agreement on the 2 products which may allow ribavirin to be used in combination with Pegasys as well.
Several studies published in August focus on the use of hormone replacement for various clinical entities. Estrogen given in high doses by skin patch may improve some cognitive skills in women with Alzheimer’s disease. Twenty women with Alzheimer’s disease were randomized to receive estradiol or placebo. The estradiol treated women improved in tests of selective attention as well as verbal and visual memory compared to placebo treated patients (Astana S, et al. Neurology. 2001;57:605-612). These findings seem to contradict recent studies that have not shown cognitive improvement with estrogen replacement. In related research, older women who take hormone replacement therapy (HRT) have smaller increases in systolic blood pressure over time than women who do not take hormones. In a longitudinal study of 226 women in Baltimore, women who did not take HRT were found to have an 18.7 mm Hg increase in systolic blood pressure over 10 years, while women who took hormones were noted to only show a 7.6 mm Hg increase over the same time period (Scuteri A, et al. Ann Intern Med. 2001;135:229-238). HRT has also been shown to increase bone mineral density in the frail elderly. Bone-related outcomes were measured in 67 women age 75 and older who were deemed frail. HRT of conjugated estrogen and medroxyprogesterone significantly increased bone mineral density of the lumbar spine and hip compared to placebo over the 9 months of the study (Villareal D, et al. JAMA. 2001;286:815-820). Finally, HRT may improve glycemic control in women with type 2 diabetes. Over 15,000 women from Northern California, followed in the Kaiser Permanente Diabetes Registry were followed for 24 months. Diabetic women on HRT (25% of the sample group) were found to have significantly lower mean HbA1c levels (average 0.5 points lower) than diabetic women not on HRT (Ferrara A, et al. Diabetes Care. 2001;24:1144-1150).