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.
Keywords: Heart failure, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor neprilysin
inhibitor, heart failure with reduced ejection fraction, heart failure with preserved ejection fraction.
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