Valsartan/sacubitril (Entresto, Novartis) is a combination of the neprilysin inhibitor sacubitril and the angiotensin receptor antagonist valsartan. In July 2015, the US Food and Drug Administration (FDA) approved valsartan/sacubitril through the fast-track pathway for the treatment of patients with New York Heart Association class II through IV heart failure symptoms and a reduced ejection fraction. The approval was based on the results of a single phase 3 clinical trial (PARADIGM-HF)1 that included 8400 patients. In this trial, valsartan/sacubitril was associated with a 20% (hazard ratio, 0.80) decrease in the primary end point of death from cardiovascular cause or first hospitalization for heart failure (from 26.5% to 21.8%), when compared with the angiotensin-converting inhibitor enalapril, and a 16% (hazard ratio, 0.84) reduction in all-cause mortality (from 19.8% to 17.0%). However, recent translational science studies involving the central nervous system and the eye suggest that other effects of valsartan/sacubitril might influence its use in some patients.