Transitioning from Losartan to Entresto (Sacubitril/Valsartan)
When switching from losartan to Entresto (sacubitril/valsartan), no washout period is required, and the transition can be made immediately at the next scheduled dose. 1
Rationale for Direct Transition
Unlike ACE inhibitors which require a 36-hour washout period before starting Entresto due to angioedema risk, ARBs like losartan can be switched directly without delay. This is because:
- ARBs do not affect bradykinin metabolism in the same way as ACE inhibitors 1
- The risk of angioedema from simultaneous inhibition of multiple bradykinin breakdown pathways is not present when switching from ARBs 1
- Losartan has a relatively short half-life (terminal half-life of its active metabolite E-3174 ranges from 6-9 hours) 2, making prolonged washout unnecessary
Dosing Recommendations for Transition
The starting dose of Entresto depends on the patient's current losartan dose:
For patients on high-dose losartan (equivalent to valsartan ≥160 mg daily):
- Start Entresto at 49/51 mg twice daily 1
For patients on low/medium-dose losartan:
- Start Entresto at 24/26 mg twice daily 1
Target dose: Increase every 2-4 weeks to reach 97/103 mg twice daily 1
Special Population Considerations
Lower starting doses (24/26 mg twice daily) are recommended for:
- Patients with severe renal impairment (eGFR <30 mL/min/1.73 m²) 1
- Patients with moderate hepatic impairment (Child-Pugh B) 1
- Elderly patients (≥75 years) 1
Monitoring After Transition
- Check renal function and electrolytes within 1-2 weeks after initiation 1
- Consider checking electrolytes and renal function 2-3 days after initiation in high-risk patients 1
- Monitor blood pressure regularly, especially in patients with baseline SBP <100 mmHg 1
- Watch for key adverse effects: hypotension, renal dysfunction, hyperkalemia, and angioedema (rare but serious) 1
Important Contraindications
Entresto should not be used in patients with:
- History of angioedema (with or without previous 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
Clinical Pearls
- The direct transition from losartan to Entresto aligns with the 2021 ACC Expert Consensus recommendation for a direct-to-ARNI approach for eligible HFrEF patients 1
- Achieving at least the middle dose (49/51 mg twice daily) of Entresto is associated with significantly better outcomes in terms of reduced heart failure hospitalizations and lower all-cause mortality 1
- While there are theoretical concerns about potential cognitive effects due to neprilysin inhibition affecting beta-amyloid clearance 3, the mortality and morbidity benefits in heart failure patients are well-established 4