Pieske B, Wachter R, Shah SJ, et al. - In patients with heart failure and left ventricular ejection factor of higher than 40%, treatment with sacubitril/valsartan conferred a significantly greater reduction in plasma N-terminal pro–brain natriuretic peptide at 12 weeks compared with standard medical therapies but failed to improve submaximal exercise capacity at 24 weeks.

• A total of 2,572 patients with heart failure and left ventricular ejection fraction higher than 40% were involved in this randomized clinical trial.

• Patients were randomly assigned 1:1 either to sacubitril/valsartan (n = 1286) or to background medication–based individualized comparator (n = 1286), ie, enalapril, valsartan, or placebo stratified by previous use of a renin angiotensin system inhibitor.

• At 12 weeks, a statistically significant decrease in plasma NT-proBNP levels (adjusted geometric mean ratio, 0.84) was brought about by sacubitril/valsartan vs standard treatment with enalapril, valsartan, or placebo.

• However, sacubitril/valsartan did not significantly alter the 6-minute walk distance at 24 weeks (9.7 m vs 12.2 m).

• In the sacubitril/valsartan group vs the comparator group, the most frequent adverse events included hypotension (14.1% vs 5.5%), albuminuria (12.3% vs 7.6%), and hyperkalemia (11.6% vs 10.9%).