How long should losartan (Angiotensin II Receptor Antagonist) be held before starting Entresto (sacubitril/valsartan)?

How Long to Hold Losartan Before Starting Entresto

When switching from losartan to sacubitril/valsartan (Entresto), no washout period is required, and the transition can be made immediately at the next scheduled dose.

Rationale for Immediate Transition from ARBs to ARNI

The 36-hour washout period requirement applies specifically to ACE inhibitors, not to Angiotensin Receptor Blockers (ARBs) like losartan. This distinction is critical for patient safety and optimal therapeutic transition.

Evidence-Based Explanation

1. ACE Inhibitors vs. ARBs Transition Requirements:

   • A 36-hour washout period is mandatory when switching from ACE inhibitors to Entresto 1
   • No washout period is required when switching from ARBs (like losartan) to Entresto 1
   • The reason for this difference relates to the risk of angioedema

2. Mechanism Behind the Washout Requirement:

   • Both ACE and neprilysin break down bradykinin 1
   • Simultaneous inhibition of both pathways significantly increases the risk of angioedema 1
   • ARBs like losartan do not affect bradykinin metabolism in the same way as ACE inhibitors

Practical Transition Protocol from Losartan to Entresto

Step 1: Determine Appropriate Starting Dose

• For patients on high-dose ARBs (valsartan ≥160 mg daily or equivalent): Start Entresto at 49/51 mg twice daily 1, 2
• For patients on low/medium-dose ARBs: Start Entresto at 24/26 mg twice daily 1, 2

Step 2: Implement the Transition

• Stop losartan
• Start Entresto at the next scheduled dose of losartan
• No washout period is required 1

Step 3: Titration Schedule

• Aim to double the dose every 2-4 weeks as tolerated 2
• Target dose: 97/103 mg twice daily 1, 2
• Monitor blood pressure, renal function, and electrolytes during titration 2

Special Considerations and Precautions

Contraindications to Entresto

• History of angioedema (with or without ACE inhibitor/ARB use) 1
• Pregnancy or lactation 1
• Severe hepatic impairment (Child-Pugh C) 1
• Concomitant use of aliskiren in patients with diabetes 1

Dose Adjustments for Special Populations

• Severe renal impairment (eGFR <30 mL/min/1.73 m²): Start at 24/26 mg twice daily 1, 2
• Moderate hepatic impairment (Child-Pugh B): Start at 24/26 mg twice daily 1, 2
• Elderly patients (≥75 years): Consider starting at 24/26 mg twice daily 1

Monitoring Recommendations

• Check renal function and electrolytes within 1-2 weeks after initiation 1, 2
• Monitor blood pressure regularly, especially in patients with baseline SBP <100 mmHg 1
• Consider checking electrolytes and renal function 2-3 days after initiation in high-risk patients 2

Clinical Pearls

• The pharmacokinetics of losartan show that its active metabolite E-3174 has a half-life of 6-9 hours 3, so there is minimal concern about residual drug effect when transitioning to Entresto
• Achieving at least the middle dose of Entresto (49/51 mg twice daily) is associated with better outcomes than remaining on the lowest dose 2
• The 2021 ACC Expert Consensus now recommends a direct-to-ARNI approach for eligible patients with heart failure with reduced ejection fraction (HFrEF) 1

Remember that while no washout period is required when switching from losartan to Entresto, careful monitoring is still essential to ensure optimal therapeutic effect and patient safety.