Which drug is a fixed combination of an ARB and neprilysin inhibitor that reduces mortality in heart failure?

• A. ACE inhibitors
• B. Sacubitril-valsartan
• C. Beta-blockers
• D. Diuretics

Answer: (B)

This item tests understanding of a heart failure therapy that combines RAAS blockade with enhanced natriuretic peptide signaling. Sacubitril-valsartan pairs an ARB (valsartan) with a neprilysin inhibitor (sacubitril). Neprilysin normally breaks down natriuretic peptides, so inhibiting it increases levels of ANP and BNP, promoting vasodilation, natriuresis, and anti-remodeling effects. The ARB component blocks angiotensin II receptors, reducing vasoconstriction, aldosterone release, and fluid retention. Together, they lower both preload and afterload while boosting beneficial natriuretic peptide activity, leading to improved outcomes in heart failure with reduced ejection fraction. This combination demonstrated a mortality reduction in a major trial (PARADIGM-HF) compared with an ACE inhibitor, establishing its survival benefit beyond symptom relief alone. Other drug classes may improve symptoms or outcomes, but they do not represent this fixed ARB plus neprilysin inhibitor with proven mortality reduction.