• See Also
  1. Systolic Dysfunction
  2. Valsartan
  3. Angiotensin 2 Receptor Blocking Agent
  • Indications
  1. Systolic Dysfunction
  • Mechanism
  1. Neprilysin Inhibitors (e.g. Sacubitril)
    1. Blocks neprilysin activity and its breakdown of natriuretic peptides
    2. Resulting prolonged natriuretic peptide activity increases vasodilation and Sodium excretion
  2. Sacubitril
    1. Prodrug that is metabolized to its active form
  3. Typical Neprilysin Inhibitor use is in combination with Angiotensin Receptor Blocker (e.g. Entresto)
    1. Adding an ARB, prevents compensatory Angiotensin activation in response to Sacubitril
  • Dosing
  1. Sacubitril and Valsartan (Entresto)
    1. Valsartan 103 mg salt in Entresto is equivalent to 160 mg salt in Diovan
    2. Start at Sacubitril/Valsartan 49/51 mg twice daily
    3. Titrate to Sacubitril/Valsartan 97/103 mg twice daily
  • Adverse Effects
  1. Combined with Valsartan (Entresto)
    1. Risk of Hypotension (Number needed to harm 21)
    2. Risk of Angioedema (Number needed to harm 200)
  • Drug Interactions
  1. Combined with Valsartan (Entresto)
    1. See Valsartan
    2. See Angiotensin 2 Receptor Blocking Agent
    3. Lithium
      1. Risk of Lithium Toxicity
  • References
  1. (2015) Presc Lett 22(9): 49
  2. McMurray (2014) N Engl J Med 371(11):993-1004 +PMID:25176015 [PubMed]