Solomon SD, McMurray JJV, Anand IS, et al. - A total of 4,822 individuals with New York Heart Association (NYHA) class II to IV heart failure, an ejection fraction of 45% or greater, increased level of natriuretic peptides, and structural heart disease were randomized to receive sacubitril–valsartan (n = 526) or valsartan (n = 557) in order to determine the impact of angiotensin receptor–neprilysin inhibition in individuals with heart failure with preserved ejection fraction. In 15.0% and 12.6% of the patients in the sacubitril–valsartan group and valsartan group, respectively, NYHA class improved, whereas renal function got worse in 1.4% and 2.7%, respectively. In the sacubitril–valsartan group, the mean-variance in the Kansas City Cardiomyopathy Questionnaire clinical summary score at 8 months was 1.0 point higher. A greater incidence of hypotension and angioedema and a lower incidence of hyperkalemia was noted in patients in the sacubitril–valsartan group. In patients with lower ejection fraction and in women, there was a hint of heterogeneity with probable advantage with sacubitril–valsartan among 12 prespecified subgroups.