Patients with heart failure who received the heart medication carvedilol suffered fewer heart attacks and strokes and were less likely to die of these and other vascular events than patients prescribed another beta blocker, metoprolol tartrate, according to a retrospective analysis of COMET (the Carvedilol or Metoprolol European Trial) published in the March 6th issue of The Journal of the American College of Cardiology.

Study investigators looked at whether the effects on vascular events contributed to the beneficial effect of carvedilol in the COMET trial, the longest and largest mortality trial comparing beta-blockers in heart failure patients. Among its key findings, the analysis documented that carvedilol reduced the risk of heart attacks, unstable angina, or stroke by 19% (p = 0.017). During the study, 106 of the 160 patients on metoprolol tartrate who had a nonfatal heart attack or stroke later died, while 61 of 124 patients on carvedilol who had a nonfatal heart attack or stroke later died.

COMET was a double-blind, randomized parallel group study designed to compare the effects of carvedilol with those of metoprolol tartrate on the risk of death and hospitalizations in patients with congestive heart failure. The study included more than 3,000 patients with heart failure primarily due to ischemic or dilated cardiomyopathy. Study participants were followed for an average of 58 months. According to COMET investigators, the study results suggested that the use of carvedilol in patients with heart failure extended median survival by 1.4 years.

The Carvedilol Or Metoprolol European Trial (COMET) compared carvedilol (target dose: 25 mg bid) to metoprolol tartrate (target dose: 50 mg bid). It is not known whether this formulation of metoprolol at any dose or this low dose of metoprolol in any formulation has any effect on survival or hospitalization in patients with heart failure. Metoprolol tartrate is not indicated in the United Statesfor heart failure. COMET did not compare carvedilol to metoprolol succinate (Toprol-XL). The efficacy of carvedilol versus metoprolol succinate in heart failure has not been established in a head-to-head outcomes study. The target dose of metoprolol succinate in heart failure is 200 mg qd. Thus this trial extends the time over which carvedilol manifests benefits on survival in heart failure, but it is not evidence that carvedilol improves outcome over the formulation of metoprolol (Toprol-XL) with benefits in heart failure.

COMET data are based on a formulation of carvedilol that patients must take twice-a-day. The FDA recently approved a once-a-day formulation of carvedilol,which is bioequivalent to the twice-a-day version and delivers the appropriate amount of medicine over a 24-hour span. GSK anticipates making this once-a-day heart medication available to physicians and their patients later this month as Coreg CR (carvedilol phosphate) Extended-Release Capsules.

COMET was jointly sponsored by GlaxoSmithKline and F. Hoffmann-La Roche.

Carvedilol is marketed by GlaxoSmithKline in the United Statesas Coreg (carvedilol) and COREG CR. It is the only beta-blocking agent FDA-approved to improve survival in patients with mild to severe heart failure. It also is the only beta-blocker the FDA has approved to reduce cardiovascular mortality in patients who had a heart attack that reduced how well the heart pumps.

COREG CR and COREG are approved to increase survival in patients with heart failure, reduce the risk of death in patients who had a heart attack that reduced how well the heart pumps, and treat hypertension, also known as high blood pressure.