Impact of candesartan on nonfatal myocardial infarction and cardiovascular death in patients with heart failure.
BACKGROUND
Angiotensin-converting enzyme (ACE) inhibitors reduce the risk of myocardial infarction (MI), but it is not known whether angiotensin receptor blockers have the same effect.


OBJECTIVE
To assess the impact of the angiotensin receptor blocker candesartan on MI and other coronary events in patients with heart failure.


METHODS
The Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) program, a randomized, placebo-controlled study enrolling patients (mean age, 66 [SD, 11] years) with New York Heart Association class II to IV symptoms who were randomly allocated to receive candesartan (target dose, 32 mg once daily) or matching placebo given in addition to optimal therapy for heart failure. Patients were enrolled from March 1999 through March 2001. Of 7599 patients allocated, 4004 (53%) had experienced a previous MI, and 1808 (24%) currently had angina. At baseline, 3125 (41%) were receiving an ACE inhibitor; 4203 (55%), a beta-blocker; 3153 (42%), a lipid-lowering drug; 4246 (56%), aspirin; and 6286 (83%), a diuretic.


METHODS
The primary outcome of the present analysis was the composite of cardiovascular death or nonfatal MI in patients with heart failure receiving candesartan or placebo.


RESULTS
During the median follow-up of 37.7 months, the primary outcome of cardiovascular death or nonfatal MI was significantly reduced in the candesartan group (775 patients [20.4%]) vs the placebo group (868 [22.9%]) (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.79-0.96; P = .004; number needed to treat [NNT], 40). Nonfatal MI alone was also significantly reduced in the candesartan group (116 [3.1%]) vs the placebo group (148 [3.9%]) (HR, 0.77; 95% CI, 0.60-0.98; P = .03; NNT, 118). The secondary outcome of fatal MI, sudden death, or nonfatal MI was significantly reduced with candesartan (459 [12.1%]) vs placebo (522 [13.8%]) (HR, 0.86; 95% CI, 0.75-0.97; P = .02; NNT, 59). Risk reductions in cardiovascular death or nonfatal MI were similar across predetermined subgroups and the component CHARM trials. There was no impact on hospitalizations for unstable angina or coronary revascularization procedures with candesartan.


CONCLUSIONS
In patients with heart failure, candesartan significantly reduces the risk of the composite outcome of cardiovascular death or nonfatal MI.
Demers
Catherine
C
McMaster University, Hamilton, Ontario, Canada.
McMurray
John J V
JJ
Swedberg
Karl
K
Pfeffer
Marc A
MA
Granger
Christopher B
CB
Olofsson
Bertil
B
McKelvie
Robert S
RS
Ostergren
Jan
J
Michelson
Eric L
EL
Johansson
Peter A
PA
Wang
Duolao
D
Yusuf
Salim
S
D000368:Aged; D000789:Angina, Unstable / Q000453:epidemiology / Q000209:etiology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy* / Q000401:mortality*; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control; D009204:Myocardial Revascularization / Q000706:statistics & numerical data; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D013777:Tetrazoles / Q000627:therapeutic use*; D016896:Treatment Outcome
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; C081643:candesartan