Angiotensin Receptor Blockers and Heart Failure Pfeffer MA, Swedberg K, Granger CB, et al for the CHARM Investigators and Committees: Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme. Lancet 2003;362(9386):759-66.
Granger CB, McMurray JJV, Yusuf S, et al for the CHARM Investigators and Committees: 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 2003;362(9386):772-76.
McMurray JJV, Ostergren J, Swedberg K, et al for the CHARM Investigators and Committees: 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 2003;362(9386):767-71.
Yusuf S, Pfeffer MA, Swedberg K, et al for the CHARM Investigators and Committees: Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: The CHARM-Preserved Trial. Lancet 2003;362(9386):777-81.
This series of articles report results of a parallel randomized double-blind controlled trial of the angiotensin receptor blocker (ARB) candesartan in 7,601 subjects with heart failure. Candesartan was titrated up to 32 mg once daily and compared with placebo in three populations: those with left ventricular ejection fraction (LVEF) <40% who were not currently receiving an angiotensin-converting-enzyme (ACE) inhibitor for some reason, those who were, and a third group whose LVEF was > 40%.
After a median of 3 years of follow-up, death rates were significantly lower in the candesartan group (23%) compared to those in the placebo (25%) (p=0.032 after adjustment for covariates). Hospital admissions were also significantly less in the candesartan group (20%) than in the placebo group (24%) ( p<0.0001). Ejection fraction or treatment at baseline did not change these effects. Study drug discontinuation rates were similar in the candesartan (30%) and the placebo (29%) groups. Patients with LVEF <40% who were already being treated with ACE inhibitors experienced significantly less death and hospitalization for CHF (38%) with candesartan compared to the placebo group (42%). Even patients with CHF and a LVEF > 40% were found to have a significantly lower risk of hospitalization in the candesartan group compared to the placebo group (p=0.01). Based on these improved outcome results, the use of ARB in CHF will likely increase.