What is the recommended use and dosing of Entresto (sacubitril/valsartan) in patients with chronic heart failure?

Entresto (Sacubitril/Valsartan) in Chronic Heart Failure Management

Sacubitril/valsartan (Entresto) is recommended as a replacement for ACE inhibitors or ARBs in patients with heart failure with reduced ejection fraction (HFrEF) who remain symptomatic despite optimal treatment, to reduce the risk of heart failure hospitalization and death. 1

Indications for Use

Entresto is indicated for:

• Patients with symptomatic chronic heart failure (NYHA class II-IV) with reduced ejection fraction (LVEF ≤40%)
• Patients who remain symptomatic despite optimal treatment with:
  • ACE inhibitor or ARB
  • Beta-blocker
  • Mineralocorticoid receptor antagonist (MRA)

Patient Selection Criteria

The ideal candidates for Entresto therapy are:

• Adults with LVEF ≤35% 1
• Patients who remain symptomatic (NYHA class II-IV) despite at least 3 months of optimal medical therapy 1
• Patients with systolic blood pressure >100 mmHg 2
• Patients with adequate renal function (eGFR >30 mL/min/1.73m²)
• Patients not experiencing angioedema with previous ACE inhibitor therapy

Dosing Protocol

Initial Dosing

• Starting dose: 24/26 mg (sacubitril/valsartan) twice daily
• For patients previously on low-dose ACE inhibitor/ARB or those with concerns for hypotension

Dose Titration

• Target dose: 97/103 mg twice daily
• Titration schedule:
  1. Start with 24/26 mg twice daily for 2-4 weeks
  2. If tolerated, increase to 49/51 mg twice daily for 2-4 weeks
  3. If tolerated, increase to target dose of 97/103 mg twice daily

Special Considerations

• For patients with severe renal impairment (eGFR <30 mL/min/1.73m²): Start with lower dose
• For patients with moderate hepatic impairment: Start with lower dose
• For elderly patients: No specific dose adjustment required, but monitor closely

Implementation Protocol

Before Initiating Therapy

1. Discontinue ACE inhibitor at least 36 hours before starting Entresto to reduce risk of angioedema
2. Check baseline blood pressure, renal function, and potassium levels
3. Assess for contraindications:
   • History of angioedema
   • Concurrent use of ACE inhibitors
   • Severe hepatic impairment
   • Pregnancy

Monitoring Protocol

• Blood pressure: At baseline, 1-2 weeks after initiation and each dose increment
• Renal function and electrolytes: At baseline, 1-2 weeks after initiation and each dose increment, then at 3 months and every 6 months thereafter
• Clinical response: Assess for improvement in heart failure symptoms at each visit

Clinical Benefits

Entresto provides significant benefits compared to ACE inhibitors alone:

• 20% reduction in the composite endpoint of cardiovascular death or heart failure hospitalization 1
• Reduction in all-cause mortality
• Improvement in quality of life and functional capacity
• Benefits observed consistently across various subgroups

Management of Common Side Effects

1. Hypotension:

   • Monitor blood pressure regularly
   • If symptomatic, consider temporary dose reduction
   • Adjust diuretic dose if needed
   • Consider modification of other antihypertensive medications

2. Renal dysfunction:

   • Monitor renal function regularly
   • If significant deterioration occurs, consider dose reduction
   • If severe, temporarily discontinue therapy

3. Hyperkalemia:

   • Monitor potassium levels regularly
   • Review and adjust potassium supplements and potassium-sparing medications
   • Consider dietary counseling regarding potassium intake

4. Angioedema:

   • Discontinue immediately if angioedema occurs
   • Provide appropriate emergency treatment
   • Do not rechallenge with Entresto or ACE inhibitors

Common Pitfalls and How to Avoid Them

1. Inadequate washout period between ACE inhibitor and Entresto:

   • Always ensure at least 36 hours between last ACE inhibitor dose and first Entresto dose
   • Failure to observe this washout period increases angioedema risk

2. Initiating at too high a dose:

   • Start with lower doses in patients previously on low-dose ACE inhibitors/ARBs
   • Gradual uptitration improves tolerability

3. Insufficient monitoring:

   • Regular monitoring of blood pressure, renal function, and electrolytes is essential
   • More frequent monitoring needed in high-risk patients (elderly, renal impairment)

4. Underutilization in eligible patients:

   • Approximately 38% of heart failure patients with reduced ejection fraction may be eligible for Entresto 2
   • Consider Entresto for all symptomatic HFrEF patients despite optimal medical therapy

5. Failure to recognize and manage side effects promptly:

   • Early recognition and management of side effects improves adherence
   • Temporary dose reduction is preferable to discontinuation

By following these guidelines, clinicians can optimize the use of Entresto in patients with chronic heart failure, potentially reducing mortality, hospitalization rates, and improving quality of life.