Transitioning from ACE Inhibitor to Entresto (Sacubitril/Valsartan)

Critical Pre-Switch Requirements

The American College of Cardiology recommends a mandatory 36-hour washout period between stopping the ACE inhibitor and starting sacubitril/valsartan to minimize the risk of angioedema in patients with heart failure 1, 2
The American College of Cardiology suggests verifying no history of angioedema related to ACE inhibitor or ARB use before initiating sacubitril/valsartan 2
The American College of Cardiology recommends ensuring hemodynamic stability, with systolic blood pressure ≥100 mm Hg, before starting sacubitril/valsartan 2
The American College of Cardiology suggests verifying renal function, with eGFR >30 mL/min/1.73 m², before initiating sacubitril/valsartan 2
The American College of Cardiology recommends ensuring the patient is not volume-depleted, as this increases hypotension risk, before starting sacubitril/valsartan 2

The American College of Cardiology recommends starting sacubitril/valsartan 24/26 mg twice daily if the patient was on a low-dose ACE inhibitor (equivalent to <10 mg enalapril daily) 1, 3
The American College of Cardiology suggests starting sacubitril/valsartan 49/51 mg twice daily if the patient was on a high-dose ACE inhibitor (equivalent to ≥10 mg enalapril daily) 1, 3

The American College of Cardiology recommends doubling the dose of sacubitril/valsartan every 2-4 weeks as tolerated, targeting the maintenance dose of 97/103 mg twice daily 1, 3
The American College of Cardiology suggests assessing tolerability at each step before advancing and monitoring blood pressure, electrolytes, and renal function after each dose increase 1, 3

The American College of Cardiology supports direct-to-ARNI initiation without prior ACE inhibitor exposure in appropriate patients, based on PIONEER-HF and PROVE-HF data showing safety and efficacy 2
The American College of Cardiology recommends sacubitril/valsartan over ACE inhibitors/ARBs in NYHA class II-III HFrEF patients, as PARADIGM-HF demonstrated a 20% relative reduction in cardiovascular death or heart failure hospitalization compared to enalapril 3