admittomedicine

angiotensin receptor-neprilysin inhibitor

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the super-inhibitor

A combination of an ARB (Valsartan) and a Neprilysin Inhibitor (Sacubitril). It augments the beneficial natriuretic peptide system (ANP/BNP) while blocking the harmful RAAS. Superior to ACEi in HFrEF.

  • Mechanism: Valsartan: Blocks Angiotensin II Type 1 receptor (RAAS blockade). Sacubitril: Inhibits Neprilysin, preventing the breakdown of ANP, BNP, and Bradykinin Vasodilation, Natriuresis.
  • Dosing: Start: 24/26 mg or 49/51 mg BID. Target: 97/103 mg BID.
  • PK: Requires a 36-hour washout period if switching from an ACE Inhibitor (risk of Angioedema).

indications

  • HFrEF: Replaces ACEi/ARB. Reduced CV death and hospitalization vs Enalapril (PARADIGM-HF).
  • HFpEF: Some benefit (FDA approved, though evidence weaker than HFrEF - PARAGON-HF).

adverse effects

  • Hypotension: More potent vasodilation than ACEi.
  • Hyperkalemia: Similar to other RAAS inhibitors.
  • Angioedema: Rare but serious (do not combine with ACEi).
  • False BNP Elevation: Sacubitril prevents BNP breakdown. Use NT-proBNP for monitoring (not a substrate for neprilysin).

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