Cardiology Forum Report

53rd Annual Scientific Session of the American College of Cardiology, March 7–10, 2004 New Orleans, Louisiana

Publication date: 2004-04-30

Heart Failure: New Analyses on the COMET Trial

This report was reviewed for medical and scientific accuracy by Ronald S. Freudenberger, MD, Director, Heart Failure and Transplant Cardiology, Associate Professor of Medicine, University of Medicine & Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, New Jersey

Expert Commentary

Philip A. Poole-Wilson, MD, FRCP, Professor of Cardiology, National Heart and Lung Institute, Faculty of Medicine, Imperial College, London, England

Results presented at the 53rd Annual Scientific Session of the American College of Cardiology provided further insight into the landmark Carvedilol or Metoprolol European Trial (COMET). The new evidence provided support for the primary finding in COMET that carvedilol had superior efficacy compared to metoprolol tartrate in reducing all-cause mortality in heart failure patients. Compared to metoprolol tartrate, the new data showed an improved survival in patients with heart failure as the result of treatment with carvedilol irrespective of blood pressure reduction,1 reduction in baseline heart rate,² and dose administered.³ The use of carvedilol was associated with lower overall costs⁴ and greater improvements in patient-reported quality of life.⁵ Another report presented at this meeting showed that compared to atenolol, the use of carvedilol in myocardial infarction patients was associated with a significant reduction in predefined cardiovascular endpoints with no difference in global or regional ejection fraction.⁶ Together these findings suggest there are important differences among beta-blocking agents which should be considered when prescribing a beta-blocker for a patient with heart failure.

Traditionally, standard therapy for heart failure has consisted of diuretics, digoxin, and angiotensin-converting-enzyme inhibitors. Despite several large clinical trials that indicate that with optimal titration and maintenance strategies, beta-blockers are efficacious and well tolerated in the treatment of heart failure, beta-blockers are still underused. The efficacy of beta-blockers in reducing morbidity and mortality in patients with heart failure has been demonstrated in the United States Carvedilol Trials Program (USCTP),⁷ the Cardiac Insufficiency Bisoprolol Study II (CIBIS-II),⁸ the Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF),⁹ and the Carvedilol Prospective Randomized Cumulative Survival trial (COPERNICUS).¹⁰ The American College of Cardiology/American Heart Association guidelines for the evaluation and management of chronic heart failure recognize beta-blocker therapy as an integral component of heart failure treatment.¹¹

Until recently, few clinical trials had directly compared the relative safety and efficacy of different beta-blockers in the treatment of patients with heart failure. The COMET trial represents the largest and longest head-to-head clinical trial of beta-blockers ever conducted in patients with heart failure.¹² The publication of COMET's primary endpoints showed a 17% relative risk reduction in terms of mortality for carvedilol over metoprolol tartrate. The median survival was prolonged by 1.4 years. An analysis of secondary endpoints indicated that carvedilol produced significant reductions in cardiovascular mortality, death from stroke, and new-onset diabetes compared with patients treated with metoprolol tartrate.¹³

This Cardiology Forum Report(tm) will examine the latest findings from the COMET trial and related data examining the use of carvedilol for heart failure as presented at the 53rd Annual Scientific Session of the American College of Cardiology.

Physiological Effects of Carvedilol and Relationships to Outcome

Carvedilol Better Protects Against Vascular Events than Metoprolol in Heart Failure: Results from COMET

Remme WJ, Cleland JG, Di Lenarda A, et al for the COMET Investigators.