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Angiotensin Receptor-Neprilysin Inhibitor (ARNI)

For complete individual drug prescribing information (PI) and updates, please refer to the drug manufacturer or FDA websites.

Initiation

De Novo

  • Initiation of an ARNI de novo without prior exposure to ACEI or ARB is now supported by recent data from clinical studies.

On ACEI/ARB

  • Ensure 36 hours off ACEI before initiating sacubitril/valsartan (ARNI) (GL). This delay is not required when switching from ARB to ARNI (EC).
  • Use of an aldosterone antagonist is not considered mandatory prior to changing a patient to ARNI (EC).

Select starting dose:

Indications Suggested initial ARNI dose
  • De novo initiation of ARNI
  • Patient on low or medium dose of ACEI (enalapril ≤ 10 mg total daily dose or therapeutically equivalent dose of another ACEI)
  • Patient on low or medium dose of ARB (valsartan ≤ 160 mg total daily dose or therapeutically equivalent dose of another ARB)
  • Severe renal impairment (eGFR < 30 mL/min/1.73m2)
  • Moderate hepatic impairment (Child-Pugh Class B)
  • Elderly (≥ 75 years old)
 24/26 mg twice daily
Patient on high dose of ACEI (enalapril > 10 mg total daily dose or therapeutically equivalent dose of another ACEI) or high dose of ARB (valsartan > 160 mg total daily dose or therapeutically equivalent dose of another ARB) with none of the indications listed above. 49/51 mg twice daily

Titration

  • In at least 2 weeks after initiation, assess tolerability (EC).
  • Carefully monitor blood pressure, electrolytes and renal function during titration (EC).
  • If possible, increase dose stepwise to target of 97/103 mg twice daily (EC).
  • Assess renal function and potassium within 1-2 weeks of dose increases (EC).
  • For optimal titration of ARNIs, lower loop diuretic doses may be necessary to permit titration. In this circumstance, careful attention to potassium concentrations is needed, as the kaluretic effects of loop diuretics may no longer be present, and restriction of supplemental and/or dietary potassium may be necessary (EC).

Monitoring

After initiation and during titration, monitor (EC):

  • Blood pressure
  • Electrolytes
  • Renal function

Contraindications and Cautions

Contraindications

  • Within 36 hours of ACEI use
  • History of angioedema with or without an ACEI or ARB
  • Pregnancy
  • Lactation (no data)
  • Severe hepatic impairment (Child-Pugh C)
  • Concomitant aliskiren use in patients with diabetes
  • Known hypersensitivity to either ARBs or ARNIs

Cautions

  • Systolic blood pressure <100 mm Hg
    -Clinicians should be advised that sacubitril/valsartan may exert a more noteworthy effect on blood pressure when compared with ACEIs/ARBs. Therefore, in patients with borderline blood pressure (e.g. systolic blood pressure ≤100 mm Hg), careful administration and follow-up are advised (EC).
  • Renal artery stenosis
  • Volume depletion

ACC/AHA/HFSA Guideline Recommendations

  • ARNI should not be administered concomitantly with ACE inhibitors or within 36 hours of the last dose of an ACE inhibitor (III, B).