Sacubitril/Valsartan (VALTRESTO) for Heart Failure with Reduced Ejection Fraction
Sacubitril/valsartan (VALTRESTO) is recommended as a replacement for ACE inhibitors or ARBs in patients with heart failure with reduced ejection fraction (HFrEF) to reduce the risk of heart failure hospitalization and death. 1
Indications
- Indicated to reduce the risk of cardiovascular death and hospitalization in adult patients with chronic heart failure and reduced ejection fraction 1
- Specifically approved for patients with symptomatic HFrEF who remain symptomatic despite optimal treatment with an ACE inhibitor/ARB, beta-blocker, and mineralocorticoid receptor antagonist 2
- Also indicated for pediatric heart failure patients aged one year and older with systemic left ventricular systolic dysfunction 1
Dosing Recommendations for Adults with HFrEF
- Starting dose: 49/51 mg orally twice daily 1
- Titration: Double the dose after 2-4 weeks to the target maintenance dose of 97/103 mg twice daily, as tolerated 1, 2
- For patients with severe renal impairment (eGFR <30 mL/min/1.73m²): Start at half the usually recommended starting dose 1
- A 36-hour washout period is required when switching from an ACE inhibitor to sacubitril/valsartan 1, 2
- No washout period is required when switching from an ARB 2
Placement in Treatment Algorithm
- First-line therapy: ACE inhibitor + beta-blocker 2, 3
- Second-line therapy: Add mineralocorticoid receptor antagonist (MRA) if patient remains symptomatic 2, 3
- Third-line therapy: Replace ACE inhibitor/ARB with sacubitril/valsartan if patient remains symptomatic despite optimal therapy with the above medications 2, 3
- Additional therapy: SGLT2 inhibitor (dapagliflozin or empagliflozin) is also recommended for HFrEF patients to reduce hospitalization and death risk 3
Clinical Benefits
- Reduces the risk of cardiovascular death and hospitalization for heart failure compared to ACE inhibitors 2, 4
- Improves NYHA functional class in approximately 37.5% of patients 5
- Improves left ventricular ejection fraction by ≥5% in 56.3% of patients after one year 5
- Reduces NT-proBNP levels by ≥30% in 39.7% of patients 5
Special Considerations and Monitoring
- Hypotension: More common with sacubitril/valsartan (12% in real-world data); consider reducing diuretic doses in non-congested patients 2, 5
- Renal function: Monitor renal function and electrolytes, particularly when used with aldosterone antagonists 2
- Hyperkalemia: Occurs in approximately 2.6% of patients 5
- Pregnancy: Contraindicated; discontinue when pregnancy is detected 1
- Drug interactions: May increase levels of statins that are substrates of OATP1B1, OATP1B3, OAT1, and OAT3 transporters 2
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
- Concomitant use with ACE inhibitors (contraindicated) 1
- Not observing the mandatory 36-hour washout period when switching from ACE inhibitors 2, 1
Potential Benefits Beyond HFrEF
- May provide benefits in heart failure with mildly reduced ejection fraction (HFmrEF, LVEF 41-49%) 2, 6
- May exhibit antiarrhythmic properties and reduce the risk of ventricular arrhythmias and sudden cardiac death 7
By following these evidence-based recommendations, clinicians can optimize the use of sacubitril/valsartan in patients with HFrEF to improve outcomes and reduce mortality and hospitalizations.