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(Circulation. 2004;110:2180-2183.)
© 2004 American Heart Association, Inc.

Heart Failure

Effect of Candesartan on Cause-Specific Mortality in Heart Failure Patients

The Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM) Program

Scott D. Solomon, MD; Duolao Wang, PhD; Peter Finn, MD; Hicham Skali, MD; Leonardo Zornoff, MD; John J.V. McMurray, MD; Karl Swedberg, MD; Salim Yusuf, MD; Christopher B. Granger, MD; Eric L. Michelson, MD; Stuart Pocock, PhD; Marc A. Pfeffer, MD, PhD

From the Cardiovascular Division, Brigham and Women’s Hospital, Boston, Mass (S.D.S., P.F., H.S., L.Z., M.A.P.); Sahlgrenska University Hospital/Östra, Göteborg, Sweden (K.S.); Duke University Medical Center, Durham, NC (C.B.G.); University of Glasgow, Glasgow, UK (J.J.V.M.); AstraZeneca LP, Wilmington, Del (E.L.M.); and Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada (S.Y.).

Correspondence to Scott D. Solomon, MD, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02445. E-mail ssolomon{at}rics.bwh.harvard.edu

Received May 5, 2004; revision received August 10, 2004; accepted August 18, 2004.

Background— Patients with heart failure are at increased risk of sudden death and death attributed to progressive pump failure. We assessed the effect of candesartan on cause-specific mortality in patients enrolled in the Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM) program.

Methods and Results— The CHARM program consisted of 3 component trials that enrolled patients with symptomatic heart failure: CHARM-Alternative (n=2028; LVEF40% and ACE intolerant), CHARM-Added (n=2548; LVEF40%, already on ACE inhibitors), and CHARM-Preserved (n=3023; LVEF >40%). Patients were randomized to candesartan, titrated to 32 mg QD, or placebo and were followed up for a median of 37.7 months. All deaths were reviewed by a blinded adjudication committee and categorized according to prespecified definitions on the basis of a narrative and source documentation. The number and rate of deaths by cause were calculated for each of the component trials and the overall program. Of all the patients, 8.5% died suddenly, and 6.2% died of progressive heart failure. Candesartan reduced both sudden death (HR 0.85 [0.73 to 0.99], P=0.036) and death from worsening heart failure (HR 0.78 [0.65 to 0.94], P=0.008). These reductions were most apparent in the patients with LVEF40%.

Conclusions— Candesartan reduced sudden death and death from worsening heart failure in patients with symptomatic heart failure, although this reduction was most apparent in patients with systolic dysfunction.

Key Words: heart failure • candesartan • receptor, angiotensin • death, sudden

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