Effect of carvedilol and metoprolol on the mode of death in patients with heart failure.
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.
Remme
Willem J
WJ
Sticares Cardiovascular Research Foundation, PO Box 882, 3160 AB Rhoon, The Netherlands. w.j.remme@sticares.org
Cleland
John G
JG
Erhardt
Leif
L
Spark
Phillip
P
Torp-Pedersen
Christian
C
Metra
Marco
M
Komajda
Michel
M
Moullet
Christine
C
Lukas
Mary Ann
MA
Poole-Wilson
Philip
P
Di Lenarda
Andrea
A
Swedberg
Karl
K
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
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D008790:Metoprolol