Comprehensive adrenergic receptor blockade with carvedilol is superior to beta-1-selective blockade with metoprolol in patients with heart failure: COMET.

The Carvedilol or Metoprolol European Trial (COMET) compared the effects of a comprehensive adrenergic antagonist, carvedilol (target dosage 25 mg twice daily), with a beta-1-selective agent, metoprolol tartrate (target dosage 50 mg twice daily), in 3029 patients with chronic heart failure caused by left ventricular systolic dysfunction. The study showed that, compared with metoprolol, long-term treatment with carvedilol exerted a substantially greater reduction in mortality and led to improvement in well-being in these patients. The superiority of carvedilol over metoprolol is readily explained by differences in their pharmacologic profiles. There is no evidence, within the trial or from other sources, that the relative dose of each agent or their formulation explained the observed difference. The result of COMET is entirely consistent with the results of previous placebo-controlled trials of beta-1-selective blockers and carvedilol.