Background: Underrepresentation of women in heart failure clinical trials has limited conclusions regarding the effect of various management strategies on survival in women with heart failure and decreased left ventricular ejection fraction (LVEF).
Methods and results: MERIT-HF (Metoprolol Extended-Release Randomized Intervention Trial in Heart Failure) was a randomized, placebo-controlled study, the purpose of which was to evaluate the effect of metoprolol controlled-release/extended-release (CR/XL) in 3991 patients with New York Heart Association class II to IV heart failure and LVEF < or =0.40. We performed a post hoc analysis to evaluate the effect of metoprolol CR/XL on outcome in women (n=898), including the outcome in 183 women with severe heart failure (New York Heart Association class III/IV and LVEF < 0.25). Treatment with metoprolol CR/XL in women resulted in a 21% reduction in the primary combined end point of all-cause mortality/all-cause hospitalizations (164 versus 137 patients; P=0.044). The number of cardiovascular hospitalizations was reduced by 29% (164 versus 120; P=0.013), and hospitalization for worsening heart failure was reduced by 42% (95 versus 56; P=0.021). Similar results were noted in the subgroup of women with severe heart failure, with a 57% reduction in cardiovascular hospitalizations (63 versus 30; P=0.005) and a 72% reduction in hospitalization due to worsening heart failure (46 versus 14; P=0.0004). A pooling of mortality results from MERIT-HF, the Cardiac Insufficiency Bisoprolol Study (CIBIS II), and the Carvedilol Prospective Randomized Cumulative Survival Study (COPERNICUS) showed very similar survival benefits in women and men.
Conclusions: The beneficial effects of metoprolol CR/XL extend to women with heart failure, including women with clinically stable severe heart failure.