There is evidence that 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. The Carvedilol or Metoprolol European Trial (COMET) was designed to compare the effects of carvedilol and metoprolol on clinical outcome (1)
- carvedilol in addition to blocking beta-1 receptors, also blocks beta-2 and alpha1 receptors. This contrasts with metoprolol which is highly selective in blocking beta-1 receptors
Design and method:
- a multicentre, double-blind, and randomised parallel group trial
- 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
- mean study duration was 58 months
Results:
- 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)
- the ejection fraction of those patients treated with carvedilol increased by approximately 9% during follow-up, whereas that of the metoprolol treated patients increased by only 5%
- incidence of side-effects and drug withdrawals did not differ by much between the two study groups
The authors of this study suggest, based on the study results, that carvedilol extends survival compared with metoprolol.
A further analysis investigated the relative effectiveness of carvedilol and metoprolol for preventing cardiovascular events (2)
- study results showed that, based on the doses of beta-blockers used in COMET, carvedilol improved vascular outcomes better than metoprolol - however note that the dose of metoprolol used in MERIT-HF was 200mg per day (not 100mg per day as used in COMET ) and this trial revealed a 39% relative risk reduction of cardiac death or non-fatal MI in the metoprolol treated group
Reference:
- (1) Lancet. 2003 Jul 5;362(9377):7-13.
- (2) Remme WJ et al. Carvedilol protects better against vascular events than metoprolol in heart failure: results from COMET. J Am Coll Cardiol. 2007 Mar 6;49(9):963-71