Cardiology Express Report

Publication date: 2003-10-25

Challenging Established Treatment Patterns: Additional Insights from COMET

Data Presented at the Symposium "Following COMET's Trail: Results and Implications of the Largest Head-to-head Mortality Trial of β-blockers in Heart Failure" held during the 7th Annual Scientific Meeting of the Heart Failure Society of America, September 22-23, 2003 in Las Vegas, Nevada.

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

Expert Commentary

Barry H. Greenberg, MD, Professor of Medicine, University of California, San Diego; Director, Heart Failure/Cardiac Transplantation Program, UCSD Medical Center, San Diego, California

An analysis of secondary endpoints data from the recently published Carvedilol or Metoprolol European Trial (COMET) indicate that treatment with carvedilol in patients with heart failure produced significant reductions in cardiovascular mortality, death from stroke, and new-onset diabetes compared with patients treated with metoprolol. These findings supplement the publication of COMET's primary endpoints, which showed a 17% mortality advantage for carvedilol over metoprolol.¹ With approximately 15,000 patient-years, COMET is the largest head-to-head trial of beta-blockers ever conducted in heart failure.

The results of COMET have generated considerable discussion among specialists in the field of cardiology. While the data unequivocally have shown that carvedilol is superior to metoprolol in terms of overall mortality at the doses and formulations used, debate continues on the dose of metoprolol (50 mg twice a day) as well as the formulation used (tartrate versus succinate).

The purpose of this Cardiology Express Report is to review the data presented on COMET and address some of the issues that continue to generate debate among cardiologists. It is my hope that continued discussion will lead to a consensus that the results of COMET support the concept that carvedilol is clearly superior to metoprolol tartrate (in doses commonly used to treat heart failure patients) in improving the clinical course. The information presented from COMET also supports the concept that the superiority of carvedilol is related to cardiovascular effects beyond those due to blockade of the beta1 adrenergic receptor alone. Overall, the primary and secondary results of COMET provide a compelling rationale for using carvedilol in treating heart failure and it is my hope that the important debate that is being conducted over the results of COMET will ultimately result in better medical treatment for the millions of heart failure patients in the United States (US) and around the world.

Introduction

Traditionally, standard therapy for heart failure has consisted of diuretics, digoxin (Lanoxin) and angiotensin converting enzyme (ACE) inhibitors. However, beta-blockers have been underused in chronic heart failure despite data from several large clinical trials that indicate that with optimal titration and maintenance strategies, beta-blockers are efficacious and well tolerated in heart failure patients indicated Philip A. Poole-Wilson, MD, Professor of Cardiology, Imperial College School of Medicine, University of London, London, England.² Dr. Wilson recited the clinical trials that have demonstrated the efficacy of beta-blockers in reducing morbidity and mortality in heart failure patients—the US Carvedilol heart failure Program (USCP),³ the Cardiac Insufficiency Bisoprolol Study II (CIBIS-II),⁴ the Metoprolol CR/XL Randomized Intervention Trial in chronic Heart Failure (MERIT-HF),⁵ and the Carvedilol Prospective Randomized Cumulative Survival trial (COPERNICUS).⁶ Beta-blockers have different pharmacological profiles a