Sacubitril

Summary

Sacubitril is a medication that is commonly co-administered with ARBs for the treatment of heart failure.

Sacubitril works to dilate blood vessels and increase natriuresis, in order to reduce the workload of the heart. Specifically, sacubitril works as a neprilysin inhibitor, which blocks the degradation of various compounds in the body, including angiotensin II, natriuretic peptides, substance P, and bradykinin.

Side effects of sacubitril include angioedema, which may become life threatening if facial swelling closes the airway. Sacubitril lowers blood pressure, which may result in hypotension and dizziness. Coughing is another side effect of taking this drug. Sacubitril is contraindicated with ACE inhibitors, so patients should wait at least 36 hours after discontinuing one of these drugs before starting the other. Additionally, the combination of sacubitril with an ARB may cause hyperkalemia in some patients, which may require monitoring through routine blood tests.

Key Points

• Sacubitril
  • Mechanism
    • Neprilysin Inhibitor
      • Neprilysin is an metalloprotease (endopeptidase) enzyme that normally works to break down other molecules
    • Prevents degradation of Natriuretic Peptides
      • Increases in ANP and BNP are thought to be primarily responsible for the drug’s clinical effects
      • Promotes natriuresis, vasodilation and reduction of ECF volume via sodium excretion
    • Prevents degradation of Bradykinin
      • Believed to result in many of the side effects, which resemble those of ACE Inhibitors
    • Prevents degradation of Angiotensin II
    • Prevents degradation of Substance P
    • ↑ Vasodilation
    • Causes Natriuresis
      • ↓  ECF (extracellular fluid) volume since sodium excretion causes water excretion in the urine
  • Clinical Use
    • Co-administered with ARBs
      • Sacubitril is often combined with Valsartan
    • Treats Heart Failure
      • Used for Heart Failure with Reduced Ejection Fraction (HFrEF)
      • May also be used to treat dilated cardiomyopathy
  • Side Effects
    • Contraindicated with use of ACE inhibitors
      • ACE Inhibitors also increase bradykinin, and when combined with Sacubitril can increase the risk of severe side effects
    • Angioedema
      • Swelling of lips, tongue, and eyelids that may close the airway
    • Cough
    • Hypotension
    • Dizziness
    • Hyperkalemia