What is the recommended dose of Entresto (sacubitril/valsartan) for a patient with heart failure with reduced ejection fraction (HFrEF)?

Entresto Dosing for Heart Failure with Reduced Ejection Fraction

The recommended starting dose of Entresto (sacubitril/valsartan) is 49/51 mg twice daily, with dose doubling every 2-4 weeks to reach the target maintenance dose of 97/103 mg twice daily. 1

Standard Dosing Algorithm

Initial Dose Selection:

• Patients on high-dose ACE inhibitors or ARBs: Start at 49/51 mg twice daily 2, 1
• Patients on low/medium-dose ACE inhibitors or ARBs: Start at 24/26 mg twice daily 2, 1
• Treatment-naïve patients (no prior ACE inhibitor/ARB): Start at 24/26 mg twice daily 2, 1

High-Risk Populations Requiring Lower Starting Dose (24/26 mg twice daily):

• Severe renal impairment (eGFR <30 mL/min/1.73 m²) 2, 1
• Moderate hepatic impairment (Child-Pugh B) 2, 1
• Elderly patients (≥75 years) 2, 1
• Patients with borderline blood pressure (systolic BP ≤100 mmHg) 2

Titration Schedule

Target dose: 97/103 mg twice daily 2, 1

• Double the dose every 2-4 weeks as tolerated 2, 1
• The European Society of Cardiology recommends this target dose provides maximum mortality benefit demonstrated in clinical trials 2
• Monitor blood pressure, renal function, and electrolytes at 1-2 weeks after each dose increment 3

Critical Timing Considerations

When switching from ACE inhibitors:

• Mandatory 36-hour washout period to avoid angioedema 2, 1

When switching from ARBs:

• No washout period required 2
• Can switch immediately 2

Managing Barriers to Optimal Dosing

Asymptomatic Hypotension:

• Do not reduce dose for asymptomatic low blood pressure with adequate perfusion 2, 3
• Entresto maintains efficacy even with systolic BP <110 mmHg 2

Symptomatic Hypotension:

• First, reduce diuretic dose in non-congested patients 2
• Consider temporarily reducing Entresto dose rather than permanent discontinuation 2
• 40% of patients requiring temporary dose reduction were successfully restored to target doses 2

Mild Creatinine Elevation:

• Increases up to 0.5 mg/dL or 30% above baseline are acceptable 2, 3
• Do not discontinue therapy for modest creatinine increases 3

Common Pitfalls to Avoid

• Never combine with ACE inhibitors - contraindicated due to angioedema risk 2, 1
• Do not accept suboptimal doses - target doses provide maximum mortality benefit 2
• Do not permanently discontinue for asymptomatic hypotension - benefits maintained regardless of baseline BP 2, 3
• Do not fail to titrate - only 1% of real-world patients achieve target doses of all HF medications simultaneously, but this should remain the goal 3

Monitoring Requirements

• Blood pressure at each visit during titration 2
• Serum creatinine and eGFR routinely, especially with aldosterone antagonists 2
• Serum potassium levels, particularly when combined with mineralocorticoid receptor antagonists 2
• Caution when potassium >5.0 mEq/L 2