PARADIGM-HF Key Finding — EECC MCQ

Correct answer: C — PARADIGM-HF showed sacubitril/valsartan reduced the composite of cardiovascular death or first HF hospitalisation by 20% and all-cause mortality by 16% compared with enalapril in HFrEF — establishing ARNI as superior to ACEi and leading to the recommendation to switch ACEi to ARNI

PARADIGM-HF (2014) is one of the most important HF trials: 8,442 patients with HFrEF (LVEF ≤40%, later amended to ≤35%) randomised to sacubitril/valsartan (97/103 mg bd) vs enalapril (10 mg bd). Terminated early for overwhelming benefit: 20% reduction in CV death or HF hospitalisation (primary composite), 16% all-cause mortality reduction, 21% HF hospitalisation reduction. Sacubitril (neprilysin inhibitor) prevents degradation of natriuretic peptides (ANP, BNP) and other vasoactive peptides, while valsartan provides RAAS blockade. The combined effect augments beneficial neurohormonal pathways while blocking harmful ones. The 2023 ESC HF Guidelines recommend ARNI in preference to ACEi for HFrEF (Class I, LOE B). The 36-hour washout from ACEi before starting ARNI is mandatory to prevent angioedema.

Reference: ESC (2023): HF Guidelines; PARADIGM-HF Trial