Mechanism and clinical benefit of sacubitril/valsartan in HFrEF is best described by which statement?

• A. Calcium channel blockade.
• B. ACE inhibition.
• C. Beta-1 receptor blockade.
• D. Neprilysin inhibition increases natriuretic peptides; ARB blocks angiotensin II receptor; reduces cardiovascular death and hospitalization in symptomatic HFrEF.

Answer: (D)

This question tests how sacubitril/valsartan works in systolic heart failure. The best description is that it combines neprilysin inhibition with an angiotensin II receptor blocker. Neprilysin inhibition increases natriuretic peptides, which promote vasodilation, natriuresis, and anti-remodeling effects. The ARB component blocks the angiotensin II receptor, reducing vasoconstriction, sodium retention, and aldosterone release. Together, these actions reduce cardiac preload and afterload and improve symptoms, while the combination has been shown to lower cardiovascular death and heart-failure–related hospitalizations in patients with symptomatic HFrEF. This mechanism is distinct from calcium channel blockade or beta-1 receptor blockade, and it is not simple ACE inhibition.