Current international guidelines recommend switching angiotensin converting enzyme inhibitors (ACE-i) or angiotensin receptor blockers (ARBs) to sacubitril/valsartan (S/V) in stable outpatients affected by heart failure with reduced ejection fraction (HFrEF) who remain symptomatic despite being on optimal medical therapy. Since these guidelines were published, new data may support further clinical applications and benefits of S/V beyond ambulatory HFrEF patients. The efficacy of S/V seems to be consistent across a wider array of subgroups including age, sex, etiology of HF, comorbidities, EF and estimated cardiovascular risk, with safety and tolerability profiles similar to ACE-I and ARBs. Additional clinical trial data are required to confirm the potential benefits of S/V in patients with mid-range or preserved EF, as suggested by analysis of PARAGON-HF, or in combination with sodium-glucose co-transporter 2 inhibitors or in post-myocardial infarction HF. In this article we summarize the new evidence on the effects and safety profile of S/V in HF and discuss current perspectives and persisting gaps. Currently, available evidence may support S/V as a first-line therapy in outpatient or in-hospital HFrEF patients, and possibly also in HFmrEF patients.
Keywords: Heart failure; Heart failure treatment; Natriuretic peptide; Sacubitril/valsartan.
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