Sacubitril is combined with valsartan (LCZ696/Entresto) in heart failure. The mechanism by which sacubitril provides benefit beyond ACE inhibitor therapy is:

• A Sacubitril directly stimulates natriuretic peptide receptors increasing cGMP
• B Sacubitril inhibits aldosterone synthase reducing sodium retention
• C Sacubitril inhibits neprilysin, preventing degradation of natriuretic peptides BNP and ANP ✓
• D Sacubitril blocks AT2 receptor signaling that causes adverse cardiac remodeling

Explanation

Sacubitril is a prodrug (converted to LBQ657) that inhibits neprilysin, a neutral endopeptidase that degrades natriuretic peptides (BNP, ANP, CNP), bradykinin, and substance P. By inhibiting neprilysin, sacubitril increases circulating natriuretic peptide levels, promoting natriuresis, vasodilation, and anti-fibrotic effects. Valsartan (ARB) is combined to block angiotensin II — since neprilysin also degrades angiotensin II, neprilysin inhibition alone would raise angiotensin II levels counterproductively.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.