Is it okay to use Entresto (sacubitril/valsartan) with an ejection fraction of 48%, given the initial recommendation for use with ejection fraction less than 40%?

Use of Entresto (Sacubitril/Valsartan) in Patients with Ejection Fraction of 48%

Yes, it is appropriate to use Entresto (sacubitril/valsartan) in patients with an ejection fraction of 48%, despite initial recommendations for use with ejection fraction less than 40%. This recommendation is based on current evidence and guidelines for heart failure management.

Evidence Supporting Use in Patients with EF of 48%

• The American College of Cardiology guidelines categorize an ejection fraction of 44% as heart failure with mildly reduced ejection fraction (HFmrEF) and indicate that patients with HFmrEF may benefit from similar medications as those with more reduced EF 1
• The FDA label for sacubitril/valsartan (Entresto) indicates it is approved "to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure and reduced ejection fraction" without specifying a strict ejection fraction cutoff 2
• Recent research demonstrates that sacubitril/valsartan provides benefits regardless of heart failure duration and can improve cardiac function across various ejection fraction ranges 3

Mechanism and Benefits

• Sacubitril/valsartan has been shown to:

  • Improve conduit vessel function 4
  • Increase functional capacity 4
  • Reduce inflammation in heart failure patients 4
  • Decrease prognostic biomarkers and reverse cardiac remodeling processes regardless of heart failure duration 3

• Treatment with sacubitril/valsartan results in:

  • Significant improvement in left ventricular diastolic function 5
  • Enhanced quality of life 5
  • Reduced risk of hospitalization due to cardiovascular events 5

Clinical Decision Algorithm

For patients with EF of 48%:

1. Assess if patient is symptomatic (NYHA class ≥II) despite optimal medical therapy 6
2. Verify the patient:
   • Has been on an ACE inhibitor or ARB for at least four weeks 2
   • Is on maximally tolerated doses of beta-blockers 2
   • Has systolic blood pressure ≥100 mmHg 2
3. If these criteria are met, initiate sacubitril/valsartan at the recommended starting dose of 49/51 mg twice daily 2
4. Titrate dose every 2-4 weeks to target maintenance dose of 97/103 mg twice daily as tolerated 2

Important Considerations and Precautions

• Contraindications include:

  • Hypersensitivity to any component 2
  • History of angioedema related to previous ACE inhibitor or ARB therapy 2
  • Concomitant use with ACE inhibitors 2
  • Concomitant use with aliskiren in patients with diabetes 2

• Monitor for:

  • Signs and symptoms of angioedema and hypotension 2
  • Renal function and potassium levels, particularly in susceptible patients 2

Conclusion

While initial recommendations focused on patients with EF <40%, current evidence supports the use of Entresto in patients with mildly reduced ejection fraction, including those with an EF of 48%. The benefits of improved cardiac function, reduced hospitalizations, and enhanced quality of life extend to this patient population.