How to safely discontinue Entresto (sacubitril/valsartan)?

Safely Discontinuing Entresto (Sacubitril/Valsartan)

When discontinuing Entresto (sacubitril/valsartan), patients should be transitioned to an appropriate ACE inhibitor or ARB after a 36-hour washout period to maintain heart failure management and prevent clinical deterioration.

Discontinuation Protocol

Step 1: Assess Need for Discontinuation

• Determine reason for discontinuation (side effects, cost issues, planned surgery, etc.)
• Evaluate current heart failure status and stability before making changes

Step 2: Plan the Transition

1. Mandatory 36-hour washout period:

   • Stop Entresto completely for at least 36 hours before starting any ACE inhibitor
   • This washout is critical to prevent angioedema risk due to overlapping neprilysin inhibition

2. Choose appropriate replacement therapy:

   • For ACE inhibitor transition: Wait full 36 hours after last Entresto dose
   • For ARB transition: Can start immediately after stopping Entresto (no washout needed)

Step 3: Dosing Considerations

• Start replacement at low dose and titrate up gradually:
  • For ACE inhibitors: Begin with low dose (e.g., enalapril 2.5mg BID)
  • For ARBs: Begin with standard starting dose (e.g., valsartan 40-80mg daily)
• Monitor blood pressure closely during transition period
• Titrate replacement medication to target dose over 2-4 weeks as tolerated

Monitoring After Discontinuation

• First week: Monitor closely for:

  • Signs of heart failure decompensation
  • Blood pressure changes
  • Renal function changes
  • Electrolyte abnormalities

• Follow-up within 1-2 weeks after transition to assess:

  • Heart failure symptoms (dyspnea, edema, fatigue)
  • Blood pressure
  • Renal function
  • Electrolytes (particularly potassium)

Important Considerations

• Risk of clinical deterioration: Studies show that discontinuation of sacubitril/valsartan can lead to worsening of LVEF and NYHA functional class even when transitioned to standard ACE inhibitor or ARB therapy 1

• Special populations:

  • Severe renal impairment: More cautious dosing of replacement therapy
  • Elderly patients: Start with lower doses and titrate more gradually
  • Patients on diuretics: Monitor fluid status closely during transition

• Medication interactions: Review all medications for potential interactions with new replacement therapy

Cautions and Pitfalls

• Never start an ACE inhibitor without the 36-hour washout after Entresto discontinuation
• Avoid periods without RAAS blockade (either Entresto, ACE inhibitor, or ARB) in heart failure patients
• Monitor for hypotension during transition period, especially with first doses of replacement therapy
• Be aware that clinical deterioration may occur despite optimal conventional therapy after switching from Entresto 1

If discontinuation is due to cost concerns rather than medical necessity, consider exploring patient assistance programs before discontinuing, as clinical outcomes may worsen with standard therapy compared to continued Entresto treatment.