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Effect of carvedilol and metoprolol on the mode of death in patients with heart failure

Remme, Willem J.; Cleland, John G.; Erhardt, Leif RW LU ; Spark, Phillip; Torp-Pedersen, Christian; Metra, Marco; Komajda, Michel; Moullet, Christine; Lukas, Mary Ann and Poole-Wilson, Philip, et al. (2007) In European Journal of Heart Failure 9(11). p.1128-1135
Abstract
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 58 months. 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... (More)
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 58 months. 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. (c) 2007 European Society of Cardiology. Published by Elsevier B.V. All rights reserved. (Less)
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published
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keywords
cardiovascular mortality, circulatory failure death, beta-blockade, heart failure, stroke death, sudden death
in
European Journal of Heart Failure
volume
9
issue
11
pages
1128 - 1135
publisher
Elsevier
external identifiers
  • wos:000251484500008
  • scopus:35548981390
ISSN
1879-0844
DOI
10.1016/j.ejheart.2007.07.014
language
English
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yes
id
7b277278-e300-4965-892b-7a539adaa044 (old id 966328)
date added to LUP
2008-01-30 08:25:12
date last changed
2017-06-04 03:43:08
@article{7b277278-e300-4965-892b-7a539adaa044,
  abstract     = {Background: In the COMET study, carvedilol improved survival compared to metoprolol tartrate in 3029 patients with NYHA II-IV heart failure and EF &lt;35%, followed for an average of 58 months. 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. (c) 2007 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.},
  author       = {Remme, Willem J. and Cleland, John G. and Erhardt, Leif RW and Spark, Phillip and Torp-Pedersen, Christian and Metra, Marco and Komajda, Michel and Moullet, Christine and Lukas, Mary Ann and Poole-Wilson, Philip and Di Lenarda, Andrea and Swedberg, Karl},
  issn         = {1879-0844},
  keyword      = {cardiovascular mortality,circulatory failure death,beta-blockade,heart failure,stroke death,sudden death},
  language     = {eng},
  number       = {11},
  pages        = {1128--1135},
  publisher    = {Elsevier},
  series       = {European Journal of Heart Failure},
  title        = {Effect of carvedilol and metoprolol on the mode of death in patients with heart failure},
  url          = {http://dx.doi.org/10.1016/j.ejheart.2007.07.014},
  volume       = {9},
  year         = {2007},
}