Sacubitril/valsartan (LCZ696) reduces mortality in heart failure with reduced ejection fraction. Sacubitril is a prodrug that is converted to the active compound LBQ657 which inhibits which enzyme to augment natriuretic peptide effects?

• A Angiotensin-converting enzyme (ACE)
• B Dipeptidyl peptidase-IV (DPP-4)
• C Neprilysin (neutral endopeptidase, NEP) ✓
• D Endothelin-converting enzyme (ECE)

Explanation

Sacubitril is a prodrug hydrolysed by esterases to LBQ657, which inhibits neprilysin (neutral endopeptidase, also called NEP or enkephalinase). Neprilysin degrades natriuretic peptides (BNP, ANP, CNP), bradykinin, and other vasodilatory peptides. Inhibiting neprilysin raises natriuretic peptide levels, promoting diuresis, natriuresis, vasodilation, and inhibition of cardiac remodelling. The valsartan component blocks AT1 receptors to prevent angiotensin II accumulation (since angiotensin II is also a neprilysin substrate). This combination is called an ARNI (angiotensin receptor-neprilysin inhibitor) and is preferred over ACE inhibitors in HFrEF patients who can tolerate it.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.