Recommended Dosage of Sacubitril for Heart Failure with Reduced Ejection Fraction
The recommended starting dose of sacubitril/valsartan for adults with heart failure with reduced ejection fraction (HFrEF) is 49/51 mg twice daily, with titration to the target maintenance dose of 97/103 mg twice daily after 2-4 weeks as tolerated by the patient. 1
Dosing Guidelines
- The initial dose of sacubitril/valsartan for adult HFrEF patients is 49/51 mg twice daily 2
- Target maintenance dose is 97/103 mg twice daily, which should be achieved after 2-4 weeks of treatment if tolerated 1, 2
- In clinical trials, the mean total daily dose achieved was 182 mg sacubitril and 193 mg valsartan 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) and titrate up as tolerated 1
Important Considerations When Initiating Therapy
- A 36-hour washout period is mandatory when switching from an ACE inhibitor to sacubitril/valsartan to avoid angioedema 2, 1
- No washout period is required when switching from an ARB to sacubitril/valsartan 2
- Sacubitril/valsartan is indicated for patients with HFrEF (EF ≤40%) with NYHA class II-IV symptoms 2
- The medication should be administered in conjunction with other guideline-directed medical therapy for heart failure 2
Clinical Evidence Supporting Dose Recommendations
- Higher doses of sacubitril/valsartan are associated with better clinical outcomes:
- Gradual titration approaches maximize attainment of target doses, especially in patients previously receiving low doses of ACEIs/ARBs 2
Special Populations and Considerations
- For patients with severe renal dysfunction, start at half the usual dose and titrate up as tolerated 1
- Early initiation of sacubitril/valsartan in patients with acute heart failure and renal dysfunction has shown improvements in estimated glomerular filtration rate and cardiac biomarkers, though these patients may require more careful monitoring 4
- The benefits of sacubitril/valsartan, including reverse cardiac remodeling and improved health status, are observed regardless of heart failure duration 5
Monitoring and Adverse Effects
- Monitor for hypotension, which occurs more frequently with sacubitril/valsartan (14.0%) compared to ACE inhibitors (9.2%) 2
- Patients with renal dysfunction have higher rates of hyperkalemia (16.3% vs 6.5%), renal impairment (6.4% vs 2.1%), and investigator-reported cardiac failure (9.7% vs 5.6%) compared to those without renal dysfunction 4
- Watch for angioedema, particularly when switching from an ACE inhibitor without observing the mandatory 36-hour washout period 2, 1
Achieving the target dose of 97/103 mg twice daily is important for maximizing mortality and morbidity benefits in HFrEF patients, but dose should be adjusted based on tolerability and specific patient characteristics, particularly renal function.