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Title: Carvedilol Confers Significant Benefit In Survival Over Metoprolol in Patients With Chronic Heart Failure

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Lancet 2003;362:7-13.
07/08/2003 10:34:41 AM
By Joene Hendry

Carvedilol has a significantly greater benefit on survival than does metoprolol for the treatment of patients with chronic heart failure who are optimally treated with diuretics and angiotensin-converting enzyme (ACE) inhibitors according to findings from the Carvedilol Or Metoprolol European Trial (COMET). Professor Philip A. Poole-Wilson, MD, of Imperial College London, United Kingdom, and colleagues compared the morbidity and mortality in patients treated with carvedilol (n=1511) or metoprolol (n=1518) for chronic heart failure in a multi-centre, randomised, double-blind trial. Study participants had symptomatic chronic heart failure (New York Heart Association class II to IV, were a mean age of 62 years, and had a mean ejection fraction of 0.26. The mean study duration was 58 months. The study medications were titrated to a target dose of twice daily 25 mg carvedilol or twice daily 50 mg metoprolol tartrate. During the maintenance phase of the study patients were assessed every 4 months. Patients with recent unstable angina, myocardial infarction, cardiac revascularisation, stroke, or changes in medications for heart failure were excluded. Also excluded were patients with uncontrolled hypertension, significant valvular disease, or other medical conditions that might affect treatment. Among patients treated with carvedilol 512 died (438 from cardiovascular causes) compared with 600 (534 from cardiovascular causes) of those taking metoprolol, giving a hazard ratio of 0.83 in favour of carvedilol. The researchers note that this mortality benefit became apparent at about 6 months of treatment. In patients treated with carvedilol mean heart rate at 4 months decreased from baseline by 13.3 beats per minute compared with a reduction from baseline of 11.7 beats per minute for those taking metoprolol, but by 16 months the heart rates did not differ between groups. The mean daily dose at entry into the maintenance phase of the study was 41.8 mg in the carvedilol group and 85 mg in the metoprolol group. Study medications were permanently stopped for reasons other than death in 32% of both treatment groups. Adverse events usually associated with beta-blockers were also similar between treatment groups. The researchers conclude that carvedilol, compared with metoprolol, extends survival in patients with chronic heart failure with an absolute reduction in mortality of 5.7% over 5 years.

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