Clinical Research
Heart Failure
Carvedilol Protects Better Against Vascular Events Than Metoprolol in Heart Failure: Results From COMET

https://doi.org/10.1016/j.jacc.2006.10.059Get rights and content
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Objectives

We explored whether vascular protection by carvedilol could contribute to its superior effects in the treatment of heart failure (HF) compared with metoprolol tartrate in the COMET (Carvedilol Or Metoprolol European Trial) study.

Background

Full adrenergic blockade by carvedilol and additional (e.g., antioxidative) properties may lead to vascular protection relative to beta-1 blockade alone, and contribute to its efficacy in HF treatment.

Methods

Three thousand twenty-nine patients with HF due to ischemic (51%) or idiopathic cardiomyopathy (44%) were randomized double-blind to carvedilol (n = 1,511) or metoprolol (n = 1,518) and followed for 58 months. Vascular end points were cardiovascular death, stroke, stroke death, myocardial infarction (MI), and unstable angina.

Results

The effect of carvedilol on cardiovascular death improved consistently in subgroups with prespecified baseline variables. Myocardial infarctions were reported in 69 carvedilol and 94 metoprolol patients (hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.52 to 0.97, p = 0.03). Cardiovascular death or nonfatal MI combined were reduced by 19% in carvedilol (HR 0.81, 95% CI 0.72 to 0.92, p = 0.0009 vs. metoprolol). Unstable angina was reported as an adverse event in 56 carvedilol and in 77 metoprolol patients (HR 0.71, 95% CI 0.501 to 0.998, p = 0.049). A stroke occurred in 65 carvedilol and 80 metoprolol patients (HR 0.79, 95% CI 0.57 to 1.10). Stroke or MI combined occurred in 130 carvedilol and 168 metoprolol patients (HR 0.75, 95% CI 0.60 to 0.95, p = 0.015), and fatal MI or fatal stroke occurred in 34 carvedilol and in 72 metoprolol patients (HR 0.46, 95% CI 0.31 to 0.69, p = 0.0002). Death after a nonfatal MI or stroke occurred in 61 of 124 carvedilol and in 106 of 160 metoprolol patients (HR 0.66, 95% CI 0.48 to 0.90, p = 0.0086).

Conclusions

Carvedilol improves vascular outcomes better than metoprolol. These results suggest a ubiquitous protective effect of carvedilol against major vascular events.

Abbreviations and Acronyms

ACE
angiotensin-converting enzyme
CI
confidence interval
HF
heart failure
HR
hazard ratio
LVEF
left ventricular ejection fraction
MI
myocardial infarction
NYHA
New York Heart Association

Cited by (0)

The COMET study was funded by F. Hoffmann-La Roche and GlaxoSmithKline. Drs. Remme, Torp-Pedersen, Cleland, Poole-Wilson, Metra, Swedberg, Komajda, and Di Lenarda have received honoraria (<$5,000 per year), travel, and accommodation expenses for their role in the Steering Committee from F. Hoffmann-La Roche. All of the Steering Committee members have received speaker’s honoraria from F. Hoffmann-La Roche Ltd. and GlaxoSmithKline at some time in the past 10 years.

1

Drs. Scherhag and Moullet are employees of F. Hoffmann-La Roche, and Dr. Lukas of GlaxoSmithKline.