Solomon SD, Vaduganathan M, Claggett BL, et al. - Researchers compared sacubitril/valsartan with a renin-angiotensin- system (RAS) inhibitor alone in two similarly designed clinical trials of patients with reduced and preserved left ventricular ejection fraction (LVEF), enabling examination of its effects across the full spectrum of LVEF. In a prespecified pooled analysis, data from PARADIGM-HF (LVEF eligibility ≤ 40%; n = 8,399) and PARAGON-HF (LVEF eligibility ≥ 45%; n = 4,796) were combined. Randomized patients (n = 13,195) were divided into LVEF categories: ≤ 22.5% (n = 1269), > 22.5% to 32.5% (n = 3987), > 32.5% to 42.5% (n = 3143), > 42.5% to 52.5% (n = 1,427), > 52.5% to 62.5% (n = 2166), > 62.5% (n = 1202). The highest vs lowest groups exhibited lower rates of cardiovascular death and HF hospitalization, but similar rates of non-cardiovascular death. For first cardiovascular death or heart failure hospitalization, cardiovascular death, heart failure hospitalization, and all-cause mortality, sacubitril/valsartan was superior to RAS inhibition. In both men and women, they noted effect modification by LVEF on the efficacy of sacubitril/valsartan with respect to composite total HF hospitalizations and cardiovascular death, although women derived benefit to higher ejection fractions.