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

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Title:	Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme.
Authors:	Pfeffer MA (AUTHOR), Swedberg K (AUTHOR), Granger CB (AUTHOR), Held P (AUTHOR), McMurray JJV (AUTHOR), Michelson EL (AUTHOR), Olofsson B (AUTHOR), Östergren J (AUTHOR), Yusuf S (AUTHOR), CHARM (Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity) Investigators and Committees (CORPORATE AUTHOR), Pfeffer, Marc A (AUTHOR), Swedberg, Karl (AUTHOR), Granger, Christopher B (AUTHOR), Held, Peter (AUTHOR), McMurray, John J V (AUTHOR), Michelson, Eric L (AUTHOR), Olofsson, Bertil (AUTHOR), Ostergren, Jan (AUTHOR), Yusuf, Salim (AUTHOR), Pocock, Stuart (AUTHOR)
Source:	Lancet. 9/6/2003, Vol. 362 Issue 9386, p759-766. 8p.
Abstract:	Background: 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.Methods: 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.Findings: 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% CI 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<0.0001) in the candesartan group. There was no significant heterogeneity for candesartan results across the component trials. More patients discontinued candesartan than placebo because of concerns about renal function, hypotension, and hyperkalaemia.Interpretation: Candesartan was generally well tolerated and significantly reduced cardiovascular deaths and hospital admissions for heart failure. Ejection fraction or treatment at baseline did not alter these effects. [ABSTRACT FROM AUTHOR]
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Database:	Psychology and Behavioral Sciences Collection
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