Heart Failure (HF) is one of the main healthcare burdens in the United States 
and in the world. Many drugs are approved and used in practice for management of 
this condition; including beta blockers, diuretics, aldosterone antagonists, 
Angiotensin Converting Enzyme Inhibitors (ACEI's), and Angiotensin Receptor 
Blockers (ARBs). Recently, the Food and Drug Administration (FDA) approved a 
drug with brand name Entresto (Sacubitril/Valsartan or LCZ696), an angiotensin 
receptor neprilysin inhibitor for the use in Heart Failure with Reduced Ejection 
Fraction (HFrEF) patients instead of ACEI's and ARBs. The drug works through 
angiotensin receptor blockage via valsartan as well as neprilysin inhibition 
with sacubitril. This represented a new milestone in managing heart failure 
patients and provided yet another therapy in our armamentarium. This article 
reviews the stages that led to the development of this drug, the failure of its 
preceding agents, the lessons we have learnt, and the current trials of Entresto 
for new indications.