Sacubitril/valsartan (Entresto) is a first-line medication for heart failure with reduced ejection fraction (HFrEF). It combines sacubitril, a neprilysin inhibitor that enhances beneficial vasodilatory peptides, with valsartan, an angiotensin receptor blocker (ARB) that reduces blood pressure and cardiac workload. This combination has been shown to significantly reduce cardiovascular death and heart failure hospitalizations compared to ACE inhibitors.

It is typically prescribed for patients with NYHA class II–IV symptoms, often in place of an ACE inhibitor or ARB, after ensuring no history of angioedema. Side effects may include hypotension, hyperkalemia, and renal dysfunction, so close monitoring is required during treatment.