title: Effect of carvedilol and metoprolol on the mode of death in patients with heart failure.
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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Sticares Cardiovascular Research Foundation, PO Box 882, 3160 AB Rhoon, The Netherlands. w.j.remme@sticares.org
authors: Willem J
authors: WJ
authors: Remme
authors: John G
authors: JG
authors: Cleland
authors: Leif
authors: L
authors: Erhardt
authors: Phillip
authors: P
authors: Spark
authors: Christian
authors: C
authors: Torp-Pedersen
authors: Marco
authors: M
authors: Metra
authors: Michel
authors: M
authors: Komajda
authors: Christine
authors: C
authors: Moullet
authors: Mary Ann
authors: MA
authors: Lukas
authors: Philip
authors: P
authors: Poole-Wilson
authors: Andrea
authors: A
authors: Di Lenarda
authors: Karl
authors: K
authors: Swedberg
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000368:Aged; D002227:Carbazoles / Q000627:therapeutic use*; D000077261:Carvedilol; D002423:Cause of Death; D016009:Chi-Square Distribution; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality*; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000627:therapeutic use*; D008875:Middle Aged; D011412:Propanolamines / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D008790:Metoprolol