Sacubitril/Valsartan

Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), has been shown to reduce the risk of cardiovascular death or heart failure hospitalization and improve symptoms among patients with chronic heart failure with reduced ejection fraction compared to enalapril, the gold standard angiotensin-converting enzyme inhibitor. In the 5 years since the publication of the results of PARADIGM-HF, further insight has been gained into integrating a neprilysin inhibitor into a comprehensive multidrug regimen, including a renin-angiotensin aldosterone system (RAS) blocker. This paper reviews the current understanding of the effects of sacubitril/valsartan and highlights expected developments over the next 5 years, including potential new indications for use. Additionally, a practical, evidence-based approach is provided to the clinical integration of sacubitril/valsartan among patients with heart failure with reduced ejection fraction. • In PARADIGM-HF, sacubitril/valsartan reduced morbidity and mortality compared to enalapril in patients with chronic HFrEF. • A series of subsequent analyses of PARADIGM-HF have provided further insight into the benefits of sacubitril/valsartan compared to enalapril. • Subsequent smaller mechanistic trials have highlighted the favorable effects of sacubitril/valsartan in attenuating adverse myocardial remodeling. • Other trials have advanced potential pathways for therapeutic implementation (including during hospitalization for heart failure). • Ongoing trials may provide evidence of new indications for sacubitril/valsartan.