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Impact of Candesartan on Nonfatal Myocardial Infarction and Cardiovascular Death in Patients With Heart Failure
Catherine Demers, MD, MSc;
John J. V. McMurray, MD;
Karl Swedberg, MD, PhD;
Marc A. Pfeffer, MD, PhD;
Christopher B. Granger, MD;
Bertil Olofsson, PhD;
Robert S. McKelvie, MD, PhD;
Jan Östergren, MD, PhD;
Eric L. Michelson, MD;
Peter A. Johansson, MSc;
Duolao Wang, PhD;
Salim Yusuf, MBBS, DPhil; for the CHARM Investigators
JAMA. 2005;294:1794-1798.
Context 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.
Design, Setting, and Participants 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  -blocker; 3153 (42%), a lipid-lowering drug; 4246 (56%), aspirin; and 6286 (83%), a diuretic.
Main Outcome Measure 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.
Conclusion In patients with heart failure, candesartan significantly reduces the risk of the composite outcome of cardiovascular death or nonfatal MI.
Author Affiliations: McMaster University, Hamilton, Ontario (Drs Demers, McKelvie, and Yusuf); University of Glasgow, Glasgow, Scotland (Dr McMurray); Sahlgrenska University Hospital/Östra, Göteborg, Sweden (Dr Swedberg); Cardiovascular Division, Brigham and Women’s Hospital, Boston, Mass (Dr Pfeffer); Duke University Medical Center, Durham, NC (Dr Granger); AstraZeneca Research and Development, Mölndal, Sweden (Dr Olofsson and Mr Johansson); Karolinska Hospital, Stockholm, Sweden (Dr Östergren); AstraZeneca LP, Wilmington, Del (Dr Michelson); and London School of Hygiene and Tropical Medicine, London, England (Dr Wang).
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