Sex differences in clinical characteristics and prognosis in a broad spectrum of patients with heart failure - Results of the candesartan in heart failure: Assessment of reduction in mortality and morbidity (CHARM) program

Background - We wished to test previous hypotheses that sex- related differences in mortality and morbidity may be due to differences in the cause of heart failure or in left ventricular ejection fraction ( LVEF) by comparing fatal and nonfatal outcomes in women and men with heart failure and a broad spectrum of left ventricular ejection fraction. Methods and Results - We compared outcomes in 2400 women and 5199 men randomized in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity ( CHARM) program using multivariable regression analyses. A total of 1188 women ( 50%) had a low LVEF ( <= 0.40), and 1212 had a preserved LVEF ( > 0.40). Among the men, 3388 ( 65%) had a low LVEF, and 1811 had a preserved LVEF. A total of 1216 women ( 51%) and 3465 men ( 67%) had an ischemic cause of their heart failure. All- cause mortality was 21.5% in women and 25.3% in men ( adjusted hazard ratio [ HR], 0.77; 95% CI, 0.69 to 0.86; P < 0.001). Fewer women ( 30.4%) than men ( 33.3%) experienced cardiovascular death or heart failure hospitalization ( adjusted HR, 0.83; 95% CI, 0.76 to 0.91; P < 0.001). The risks of sudden death ( HR, 0.70; 95% CI, 0.58 to 0.85) and death due to worsening heart failure ( HR, 0.72; 95% CI, 0.58 to 0.89) were reduced to a comparable extent. The adjusted risk of cardiovascular hospitalization was also lower in women ( HR, 0.88; 95% CI, 0.82 to 0.95), mainly because of a reduced risk of heart failure hospitalization ( HR, 0.87; 95% CI, 0.78 to 0.97). Women had a lower risk of death irrespective of cause of heart failure or LVEF. Conclusions - Among patients with heart failure, women have lower risks of most fatal and nonfatal outcomes that are not explained, as previously suggested, by LVEF or origin of the heart failure.