CHARM program (clinical trials)

Placebo-controlled trials in patients with chronic heart failure. Study characteristics: candesartan 32 mg QD (target dose) vs placebo. 3 arm trial 1) 2548 patients with LVEF < 40% already taking ACE inhibitor 2) 2028 patients with reduced LVEF intolerant of ACE inhibitors 3) 3023 patients with LVEF > 40% (19% taking ACE inhibitor) Mean follow-up of 38 months Results: 1) candesartan improved: a) cardiovascular death b) rehospitalization for heart failure c) probably* all-cause mortality (23% vs 25%) 2) benefit greatest for patients with systolic dysfunction 3) no evidence of adverse reaction with combination of: a) ACE inhibitor b) candesartan (ARB) c) beta-blocker * difference significant after adjustment for potentially confounding clinical variables

References

- Journal Watch 23(21):166, 2003 - Pfeffer MA et al Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet 362:759, 2003 PMID: 13678868 - McMurray JJV et al Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial. Lancet 362:767, 2003 PMID: 13678869 - Granger CB et al, Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial. Lancet 362:772, 2003 PMID: 13678870 - Yusuf S et al Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial. Lancet 362:777, 2003 PMID: 13678871 - White HD Candesartan and heart failure: the allure of CHARM Lancet 362:754, 2003 PMID: 13678864