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: The Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM) program

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.