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on October 4, 2004

A more recent version of this article appeared on October 12, 2004

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Submitted on May 5, 2004
Revised on August 10, 2004
Accepted on August 18, 2004

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, and 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.).

^* To whom correspondence should be addressed. E-mail: ssolomon{at}rics.bwh.harvard.edu.

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; LVEF=40% and ACE intolerant), CHARM-Added (n=2548; LVEF=40%, 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 LVEF=40%.

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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