Dosage of Sacubitril/Valsartan for Heart Failure with Reduced Ejection Fraction
The recommended starting dose of sacubitril/valsartan is 49/51 mg twice daily for most patients with heart failure with reduced ejection fraction (HFrEF), with titration to the target maintenance dose of 97/103 mg twice daily after 2-4 weeks as tolerated by the patient. 1
Initial Dosing Recommendations
- For patients previously on high-dose ACE inhibitors or ARBs, start with 49/51 mg twice daily 2
- For patients on low/medium-dose ACE inhibitors or ARBs, or treatment-naïve patients, start with 24/26 mg twice daily 2
- For patients with severe renal impairment (eGFR <30 mL/min/1.73 m²), start at half the usually recommended dose (24/26 mg twice daily) 1
- For patients with moderate hepatic impairment (Child-Pugh B), start with 24/26 mg twice daily 3
- For elderly patients (≥75 years), consider starting with the lower dose of 24/26 mg twice daily 2
Titration Schedule
- Double the dose every 2-4 weeks as tolerated to reach the target maintenance dose of 97/103 mg twice daily 1
- In real-world practice, many patients start at the lowest dose (24/26 mg twice daily) and may remain on this dose for extended periods 4
- Studies show that only about 17% of patients achieve the target dose of 97/103 mg twice daily after 4 months of treatment in real-world settings 4
Important Precautions
- A 36-hour washout period is mandatory when switching from an ACE inhibitor to sacubitril/valsartan to avoid risk of angioedema 1
- No washout period is required when switching from an ARB to sacubitril/valsartan 2
- Monitor for symptomatic hypotension, especially during initiation and dose titration 2
- Consider reducing diuretic doses in non-congested patients to mitigate hypotensive effects 2
- Monitor renal function and electrolytes, particularly when used with aldosterone antagonists 2
Special Considerations
- For patients with borderline blood pressure (systolic BP ≤100 mm Hg), careful administration and follow-up is recommended 2
- For patients experiencing hypotension, consider temporarily reducing the dose rather than discontinuing therapy completely 2
- Studies show that patients initiated on very low doses (25 mg twice daily) due to concerns about hypotension can still achieve clinical benefits similar to those on standard doses 5
- Recent data support direct initiation of sacubitril/valsartan without a pretreatment period with ACEIs or ARBs as a safe and effective strategy 3
Common Pitfalls to Avoid
- Failure to titrate to target doses due to asymptomatic hypotension or mild laboratory changes 2
- Permanent dose reductions when temporary reductions with subsequent re-titration would be more appropriate 2
- Discontinuing therapy completely when dose adjustments could maintain patients on this beneficial medication 2
- Not allowing adequate washout period (36 hours) when switching from ACE inhibitors 1
Clinical Benefits
- Even at lower doses, sacubitril/valsartan has been shown to reduce NT-proBNP levels and improve left ventricular ejection fraction 5
- Real-world data show improvements in symptoms (fatigue, shortness of breath) and reduction in hospitalizations within 4 months of treatment initiation 4
- Benefits are observed regardless of heart failure duration, with improvements in cardiac biomarkers, health status, and cardiac remodeling 6