Heart Failure Management with Sacubitril/Valsartan

Introduction to Transition Requirements

When switching from Angiotensin Receptor Blockers (ARBs) like losartan to Entresto (sacubitril/valsartan), no washout period is required, and the transition can be made immediately at the next scheduled dose, as recommended by the American College of Cardiology 1
A 36-hour washout period is mandatory when switching from ACE inhibitors to Entresto, due to the risk of angioedema, as stated by the American College of Cardiology and the American Heart Association 1, 2

The mechanism behind the washout requirement is related to the breakdown of bradykinin by both ACE and neprilysin, and simultaneous inhibition of both pathways significantly increases the risk of angioedema, according to the American Heart Association 2
ARBs like losartan do not affect bradykinin metabolism in the same way as ACE inhibitors, which is why no washout period is required when switching from ARBs to Entresto, as recommended by the American College of Cardiology 1

For patients on high-dose ARBs (equivalent to valsartan ≥160 mg daily), the American College of Cardiology recommends starting Entresto at 49/51 mg twice daily 1
For patients on low/medium-dose ARBs, the American College of Cardiology recommends starting Entresto at 24/26 mg twice daily 1
The target dose of Entresto is 97/103 mg twice daily, as recommended by the American College of Cardiology 1
The dose should be increased every 2-4 weeks to target a dose of 97/103 mg twice daily, as recommended by the American College of Cardiology 3

History of angioedema (with or without ACE inhibitor/ARB use) is a contraindication for Entresto, as stated by the American College of Cardiology and the American Heart Association 1, 2
Pregnancy or lactation is a contraindication for Entresto, according to the American College of Cardiology 1
Severe hepatic impairment (Child-Pugh C) is a contraindication for Entresto, as recommended by the American College of Cardiology 1
Concomitant use of aliskiren in patients with diabetes is a contraindication for Entresto, according to the American College of Cardiology 1

Severe renal impairment (eGFR <30 mL/min/1.73 m²) requires a starting dose of 24/26 mg twice daily, as recommended by the American College of Cardiology 1
Moderate hepatic impairment (Child-Pugh B) requires a starting dose of 24/26 mg twice daily, according to the American College of Cardiology 1
Elderly patients (≥75 years) should be considered for a starting dose of 24/26 mg twice daily, as recommended by the American College of Cardiology 1

Renal function and electrolytes should be checked within 1-2 weeks after initiation of Entresto, as recommended by the American College of Cardiology 1
Blood pressure should be monitored regularly, especially in patients with baseline SBP <100 mmHg, according to the American College of Cardiology 1
Monitoring of blood pressure, electrolytes, and renal function is recommended after initiation and during titration 1
Consider checking electrolytes and renal function 2-3 days after initiation 1
Key adverse effects to monitor include hypotension, renal dysfunction, hyperkalemia, and angioedema (rare but serious) 1

The 2021 ACC Expert Consensus recommends a direct-to-ARNI approach for eligible patients with heart failure with reduced ejection fraction (HFrEF), as stated by the American College of Cardiology 1
Achieving at least the middle dose (49/51 mg twice daily) of sacubitril/valsartan is associated with significantly better outcomes than the lowest dose (24/26 mg twice daily) in terms of reduced heart failure hospitalizations and lower all-cause mortality 1