Sacubitril/valsartan (Entresto™; LCZ696) is an orally administered 
supramolecular sodium salt complex of the neprilysin inhibitor prodrug 
sacubitril and the angiotensin receptor blocker (ARB) valsartan, which was 
recently approved in the US and the EU for the treatment of chronic heart 
failure (NYHA class II-IV) with reduced ejection fraction (HFrEF). In the large, 
randomized, double-blind, PARADIGM-HF trial, sacubitril/valsartan reduced the 
incidence of death from cardiovascular causes or first hospitalization for 
worsening heart failure (composite primary endpoint) significantly more than the 
angiotensin converting enzyme (ACE) inhibitor enalapril. Sacubitril/valsartan 
was also superior to enalapril in reducing death from any cause and in limiting 
the progression of heart failure. Sacubitril/valsartan was generally well 
tolerated, with no increase in life-threatening adverse events. Symptomatic 
hypotension was significantly more common with sacubitril/valsartan than with 
enalapril; the incidence of angio-oedema was low. Therefore, 
sacubitril/valsartan is a more effective replacement for an ACE inhibitor or an 
ARB in the treatment of HFrEF, and is likely to influence the basic approach to 
treatment.