Elsevier

American Heart Journal

Volume 149, Issue 2, February 2005, Pages 370-376
American Heart Journal

Clinical investigation
Effects of metoprolol and carvedilol on cause-specific mortality and morbidity in patients with chronic heart failure—COMET

https://doi.org/10.1016/j.ahj.2004.10.002Get rights and content

Background

β-Blockers with different receptor bindings reduce mortality in patients with chronic heart failure. We compared the effects of the β1-blocker metoprolol tartrate and the β1-, β2-, and α1-blocker carvedilol.

Methods

In a randomized double-blind design, 3029 patients with chronic congestive heart failure requiring diuretic therapy and with left ventricular dysfunction were randomized to treatment with carvedilol (n = 1511) or metoprolol tartrate (n = 1518) and titrated to target doses of 25 mg of carvedilol twice daily or 50 mg of metoprolol tartrate twice daily. The main outcome measures were total mortality and the combination of mortality or hospitalization for any cause. Secondary end points were cardiovascular death, combinations of morbidity and mortality, New York Heart Association class, worsening of heart failure, hospitalizations, and discontinuation of study therapy.

Results

A total of 512 and 600 patients in the carvedilol group and metoprolol group, respectively, died (hazard ratio [HR] 0.83, 95% CI 0.74-0.93, P = .0017). Cardiovascular death was reduced by carvedilol (HR 0.80, 95% CI 0.70-0.90, P = .0004). There were fewer sudden deaths and deaths caused by circulatory failure or by stroke in the carvedilol group. There was no difference in all-cause hospitalizations or in worsening heart failure between treatment groups. The incidence of fatal or nonfatal acute myocardial infarction was significantly lower in the carvedilol group (HR 0.71, 95% CI 0.52-0.97, P = .03). Discontinuations of study therapy were similar in the 2 groups.

Conclusion

Compared with metoprolol tartrate, carvedilol reduced cardiovascular mortality, sudden death, death caused by circulatory failure, death caused by stroke, as well as fatal and nonfatal myocardial infarctions.

Section snippets

Methods

The COMET was a randomized, double-blind, parallel group trial comparing carvedilol with metoprolol for the treatment of chronic heart failure. Details of the study design have been published previously.14., 15. A total of 3029 patients with chronic heart failure was randomized in 316 centers in 15 European countries. Patients were recruited between December 1996 and January 1999. Follow-up was concluded in November 2002.

An end point committee classified all fatal events and cases of acute

Results

A total of 3029 patients was randomized, 1511 and 1518 to carvedilol and metoprolol, respectively. The 2 study groups were well matched (see Table I). The mean study duration was 58 ± 6 months (time from randomization to study closure). The profile of the study is shown in Figure 1 and the baseline characteristics are shown in Table I. The mean decrease in systolic blood pressure after 4 months in patients undergoing treatment was 3.8 mm Hg in the carvedilol group and 2.0 mm Hg in the

Discussion

The COMET study demonstrates that treatment of patients with chronic heart failure with carvedilol compared with metoprolol tartrate improves survival. Cardiovascular death was particularly reduced. Modes of cardiovascular death, sudden death, death caused by circulatory failure, and death caused by stroke were all reduced by carvedilol as compared with metoprolol. There was also a significant reduction in the risk of fatal or nonfatal myocardial infarctions by carvedilol.

Mode of death was

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  • Cited by (0)

    1

    The COMET investigators are listed in a previous publication.1

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