Switching from Losartan to Sacubitril/Valsartan (Entresto): Dosing Guidelines
When switching from losartan to sacubitril/valsartan (Entresto), a 36-hour washout period is required before initiating sacubitril/valsartan at a starting dose of 49/51 mg twice daily, with the goal of uptitrating to the target dose of 97/103 mg twice daily within 2-4 weeks as tolerated. 1, 2
Transition Process
Step 1: Washout Period
- Discontinue losartan for 36 hours before starting sacubitril/valsartan to prevent risk of angioedema 1
- This washout period is mandatory for all patients transitioning from any ACE inhibitor, but also applies when switching from ARBs like losartan 1
Step 2: Initial Dosing
- For most patients, start with sacubitril/valsartan 49/51 mg twice daily 2
- For patients with severe renal impairment (eGFR <30 mL/min/1.73 m²), start at half the recommended dose: 24/26 mg twice daily 1, 2
- For patients with moderate hepatic impairment (Child-Pugh B), start at 24/26 mg twice daily 2
Step 3: Uptitration Schedule
- Increase dose every 2-4 weeks to target dose of 97/103 mg twice daily 1, 2
- Monitor blood pressure, electrolytes, and renal function after initiation and during titration 2
- Consider checking electrolytes and renal function 2-3 days after initiation 2
Special Considerations
Dosing Based on Previous Losartan Dose
- For patients on low-dose losartan (<50 mg daily), a more conservative uptitration approach may be beneficial 3
- For patients on high-dose losartan (≥50 mg daily), either conservative or condensed uptitration approaches show similar tolerability 3
Monitoring for Adverse Effects
- Key adverse effects to monitor include:
Contraindications
- History of angioedema
- Pregnancy
- Severe hepatic impairment (Child-Pugh C)
- Concomitant aliskiren use in patients with diabetes 2
Clinical Outcomes and Dose Considerations
Recent evidence shows that 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 (19.51% vs. 29.14%)
- Lower all-cause mortality (17.58% vs. 29.63%) 4
The target dose of 97/103 mg twice daily showed even greater benefits with:
- Further reduced heart failure hospitalizations (16.10%)
- Lower all-cause mortality (9.27%) 4
Timing of Initiation
For patients hospitalized with heart failure, sacubitril/valsartan can be initiated either pre-discharge (≥12 hours before discharge) or within 1-14 days post-discharge with similar tolerability and achievement of target doses 5
Common Pitfalls to Avoid
- Failing to observe the mandatory 36-hour washout period
- Uptitrating too rapidly in patients with renal impairment
- Not adjusting diuretic doses when initiating sacubitril/valsartan, which may contribute to hypotension
- Discontinuing therapy prematurely due to transient eGFR decline, which often recovers and does not affect long-term benefits 6
- Settling for the lowest dose (24/26 mg twice daily) when higher doses are tolerated, as higher doses are associated with better outcomes 4
Remember that transient changes in kidney function upon transition to sacubitril/valsartan are common and do not necessarily predict adverse outcomes or diminish the treatment benefits of continuing sacubitril/valsartan 6.