Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme

Patients with chronic heart failure (CHF) are at high risk of cardiovascular death and recurrent hospital admissions. We aimed to find out whether the use of an angiotensin-receptor blocker could reduce mortality and morbidity. In parallel, randomised, double-blind, controlled, clinical trials we compared candesartan with placebo in three distinct populations. We studied patients with left-ventricular ejection fraction (LVEF) 40% or less who were not receiving angiotensin-converting-enzyme inhibitors because of previous intolerance or who were currently receiving angiotensin-converting-enzyme inhibitors, and patients with LVEF higher than 40%. Overall, 7601 patients (7599 with data) were randomly assigned candesartan (n=3803, titrated to 32 mg once daily) or matching placebo (n=3796), and followed up for at least 2 years. The primary outcome of the overall programme was all-cause mortality, and for all the component trials was cardiovascular death or hospital admission for CHF. Analysis was by intention to treat. Median follow-up was 37·7 months. 886 (23%) patients in the candesartan and 945 (25%) in the placebo group died (unadjusted hazard ratio 0·91 [95% Cl 0·83–1·00], p=0·055; covariate adjusted 0·90 [0·82–0·99], p=0·032), with fewer cardiovascular deaths (691 [18%] vs 769 [20%], unadjusted 0·88 [0·79–0·97], p=0·012; covariate adjusted 0·87 [0·78–0·96], p=0·006) and hospital admissions for CHF (757 [20%] vs 918 [24%], p