The PARADIGM-HF study, a large outcome trial in heart failure and reduced 
ejection fraction (HFrEF), has recently shown improved cardiovascular outcomes 
with sacubitril/valsartan (Entresto®, Novartis), still commonly referred to as 
LCZ696, compared to ACE-inhibitor therapy, possibly leading us to a new era for 
heart failure (HF) treatment. LCZ696 represents a first-in-class drug acting 
through inhibition of angiotensin receptor and neprilysin, thus modulating the 
renin angiotensin aldosterone system and vasoactive substances such as 
natriuretic peptides. Based on the PARADIGM-HF results, the FDA recently 
approved LCZ696 as an effective means to reduce the burden of HF with reduced 
ejection fraction. Furthermore, these data also provided rationale to test 
LCZ696 in an ongoing trial with HF and preserved ejection fraction. Despite the 
enthusiasm regarding this novel compound, real world data on its efficacy and 
safety are eagerly expected. This article summarizes all evidences regarding 
LCZ696 and how to implement this new drug in the current HF armamentarium.