© 2007 European Society of Cardiology
Effect of carvedilol and metoprolol on the mode of death in patients with heart failure
a Sticares Cardiovascular Research Foundation P.O. Box 882, 3160 AB Rhoon, The Netherlands
b Department of Cardiology, Castle Hill Hospital, University of Hull Kingston upon Hull, UK
c Cardiology Research Unit, University Hospital MAS Malmö, Sweden
d Nottingham Clinical Research Group Nottingham, UK
e Department of Cardiology, Bispebjerg University Hospital Copenhagen, Denmark
f Department of Cardiology, University of Brescia Brescia, Italy
g Department of Cardiology, CHU Pitié-Salpétrière Paris, France
h F. Hoffmann-LaRoche, Basel, Switzerland
i GlaxoSmithKline, Philadelphia, Pennsylvania, USA
j Department of Cardiac Medicine, National Heart & Lung Institute London, UK
k University of Trieste Trieste, Italy
l Sahlgrenska Hospital Gothenburg, Sweden
* Corresponding author. Tel.: #x002B;31 10 485 51 77; fax: +31 10 485 48 33. E-mail address:w.j.remme{at}sticares.org
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Abstract |
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Background: In the COMET study, carvedilol improved survival compared to metoprolol tartrate in 3029 patients with NYHA II–IV heart failure and EF <35%, followed for an average of 58months.
Aims: To evaluate whether the effect on overall mortality was specific for a particular mode of death. This may help to identify the mechanism of the observed difference.
Methods: Of the 1112 total deaths, 972 were adjudicated as cardiovascular, including 480 sudden, 365 circulatory failure (CF) and 51 stroke deaths. For each mode of death, the effect of pre-specified baseline variables was assessed, including sex, age, NYHA class, aetiology, heart rate, systolic blood pressure, EF, atrial fibrillation, previous myocardial infarction or hypertension, renal function, concomitant medication, and study treatment allocation.
Results: In multivariate Cox regression analyses, compared to metoprolol, carvedilol reduced cardiovascular (RR 0.80, CI 0.7–0.91, p=0.0009), sudden (RR 0.77, CI 0.64–0.93, p=0.0073) and stroke deaths (RR 0.37, CI 0.19–0.71, p=0.0027) with a non-significant trend for CF death (RR 0.83, CI 0.66–1.04, p=0.07). Treatment benefit with carvedilol did not differ between modes of death, except for a greater reduction in stroke death with carvedilol (competing risk analysis, p=0.0071 vs CF death). There were no interactions between treatment allocation and baseline characteristics.
Conclusion: Mortality reduction with carvedilol compared to metoprolol appears relatively non-specific and could be consistent with a superior effect of carvedilol on cardiac function, arrhythmias or, in view of the greater reduction in stroke deaths, on vascular events.
Key Words: Heart failure • β-blockade • Cardiovascular mortality • Sudden death • Stroke death • Circulatory failure death
Received December 19, 2006; Revised June 21, 2007; Accepted July 24, 2007
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