Carvedilol shown to improve survival when compared to metoprolol 12 May, 2003:

Results of the first-ever head-to-head mortality study comparing two beta blocking agents in patients with chronic heart failure (CHF) were announced today. The COMET study met its primary mortality endpoint showing a significant improvement of survival for carvedilol when compared to metoprolol. The Carvedilol or Metoprolol European Trial (COMET) was designed to investigate whether comprehensive _-1, _-2, _-1 blockade with carvedilol was superior to _-1 selective blockade with metoprolol in the treatment of patients with CHF. “COMET is the longest and largest study ever conducted in chronic heart failure with more than 10,000 patient years of follow-up” commented Professor Philip Poole- Wilson, Chairman of the COMET Steering Committee. “The significant survival benefits of carvedilol demonstrate a clear difference between the agents”.

Beta blockers are recommended in the guidelines of major international societies such as the European Society of Cardiology (ESC)1 the American Heart Association (AHA) and the American College of Cardiology (ACC)2 for the treatment of mild, moderate and severe chronic heart failure, and have been clinically proven in a number of landmark clinical trials.3,4,5 COMET’s principal results will first be presented at the Heart Failure 2003 meeting, organised by the European Society of Cardiology, 21-24 June, in Strasbourg, France.

About Chronic Heart Failure

Experts suggest that there may be more than 10 million people with CHF in Europe alone. There are approximately 2-3 new cases of CHF per 1,000 of the population per year in Europe, whilst in the US there are 400,000 new cases diagnosed annually. Prognosis for CHF is generally poor, with around half of all patients diagnosed dying within 3-5 years - a death rate similar to that of patients with lung cancer. Quality of life for patients, especially with more severe disease, is low.

Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomised controlled trial.

Poole-Wilson PA, Swedberg K, Cleland JG, Di Lenarda A, Hanrath P, Komajda M, Lubsen J, Lutiger B, Metra M, Remme WJ, Torp-Pedersen C, Scherhag A, Skene A; Carvedilol Or Metoprolol European Trial Investigators.

National Heart and Lung Institute, Imperial College, London, UK. p.poole-wilson@imperial.ac.uk

BACKGROUND: Beta blockers reduce mortality in patients who have chronic heart failure, systolic dysfunction, and are on background treatment with diuretics and angiotensin-converting enzyme inhibitors. We aimed to compare the effects of carvedilol and metoprolol on clinical outcome. METHODS: In a multicentre, double-blind, and randomised parallel group trial, we assigned 1511 patients with chronic heart failure to treatment with carvedilol (target dose 25 mg twice daily) and 1518 to metoprolol (metoprolol tartrate, target dose 50 mg twice daily). Patients were required to have chronic heart failure (NYHA II-IV), previous admission for a cardiovascular reason, an ejection fraction of less than 0.35, and to have been treated optimally with diuretics and angiotensin-converting enzyme inhibitors unless not tolerated. The primary endpoints were all-cause mortality and the composite endpoint of all-cause mortality or all-cause admission. Analysis was done by intention to treat. FINDINGS: The mean study duration was 58 months (SD 6). The mean ejection fraction was 0.26 (0.07) and the mean age 62 years (11). The all-cause mortality was 34% (512 of 1511) for carvedilol and 40% (600 of 1518) for metoprolol (hazard ratio 0.83 [95% CI 0.74-0.93], p=0.0017). The reduction of all-cause mortality was consistent across predefined subgroups. The composite endpoint of mortality or all-cause admission occurred in 1116 (74%) of 1511 on carvedilol and in 1160 (76%) of 1518 on metoprolol (0.94 [0.86-1.02], p=0.122). Incidence of side-effects and drug withdrawals did not differ by much between the two study groups. INTERPRETATION: Our results suggest that carvedilol extends survival compared with metoprolol.

Publication Types:

· Clinical Trial
· Randomized Controlled Trial

PMID: 12853193 [PubMed - indexed for MEDLINE]