A 55-year-old man with HFrEF (EF 30%) is on optimal medical therapy with metoprolol succinate, enalapril, and furosemide. His NT-proBNP is 3800 pg/mL. The PARADIGM-HF trial established which new therapeutic class that should be incorporated into his treatment?
- A SGLT2 inhibitors (empagliflozin) — EMPEROR-Reduced trial
- B Ivabradine — SHIFT trial benefit in sinus tachycardia >70 bpm
- C Aldosterone antagonist — RALES trial evidence
- D Angiotensin receptor-neprilysin inhibitor — sacubitril/valsartan replacing ACE inhibitor ✓
Explanation
The PARADIGM-HF trial demonstrated that sacubitril/valsartan (ARNI: angiotensin receptor blocker + neprilysin inhibitor) reduced cardiovascular death and HF hospitalisation by 20% compared to enalapril in HFrEF patients. Sacubitril inhibits neprilysin, preventing degradation of natriuretic peptides (ANP/BNP), thereby promoting natriuresis and vasodilation. ACC/AHA guidelines now recommend switching from ACE inhibitor to sacubitril/valsartan in stable HFrEF patients who tolerate RAAS inhibition. An SGLT2 inhibitor (EMPEROR-Reduced and DAPA-HF trials) is now also part of the 'Fantastic Four' pillars of HFrEF therapy along with ARNI/ACEI, beta-blocker, and MRA.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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Written and medically reviewed by the StethoPrep medical team.