Prevention of atrial fibrillation in patients with symptomatic chronic heart failure by candesartan in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) program.
BACKGROUND
Atrial fibrillation (AF) is frequent in patients with chronic heart failure (CHF). Experimental and small patient studies have demonstrated that blocking the renin-angiotensin-aldosterone system may prevent AF. In the CHARM program, the effects of the angiotensin receptor blocker candesartan on cardiovascular mortality and morbidity were evaluated in a broad spectrum of patients with symptomatic CHF. CHARM provided the opportunity to prospectively determine the effect of candesartan on the incidence of new AF in this CHF population.


METHODS
7601 patients with symptomatic CHF and reduced or preserved left ventricular systolic function were randomized to candesartan (target dose 32 mg once daily, mean dose 24 mg) or placebo in the 3 component trials of CHARM. The major outcomes were cardiovascular death or CHF hospitalization and all-cause mortality. The incidence of new AF was a prespecified secondary outcome. Median follow-up was 37.7 months. A conditional logistic regression model for stratified data was used.


RESULTS
6379 patients (83.9%) did not have AF on their baseline electrocardiogram. Of these, 392 (6.15%) developed AF during follow-up, 177 (5.55%) in the candesartan group and 215 (6.74%) in the placebo group (odds ratio 0.812, 95% CI 0.662-0.998, P = .048). After adjustment for baseline covariates, the odds ratio was 0.802 (95% CI 0.650-0.990, P = .039). There was no heterogeneity of the effects of candesartan in preventing AF between the 3 component trials (P = .57).


CONCLUSIONS
Treatment with the angiotensin receptor blocker candesartan reduced the incidence of AF in a large, broadly-based, population of patients with symptomatic CHF.
Ducharme
Anique
A
Montreal Heart Institute, Montreal, Quebec, Canada. a_ducharme@icm-mhi.com
Swedberg
Karl
K
Pfeffer
Marc A
MA
Cohen-Solal
Alain
A
Granger
Christopher B
CB
Maggioni
Aldo P
AP
Michelson
Eric L
EL
McMurray
John J V
JJ
Olsson
Lars
L
Rouleau
Jean L
JL
Young
James B
JB
Olofsson
Bertil
B
Puu
Margareta
M
Yusuf
Salim
S
D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000453:epidemiology / Q000503:physiopathology / Q000517:prevention & control*; D001562:Benzimidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D015897:Comorbidity; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use*
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; C081643:candesartan