How to manage Entresto (sacubitril/valsartan) in patients with impaired renal function?

Managing Entresto (Sacubitril/Valsartan) in Patients with Impaired Renal Function

For patients with moderate renal impairment (eGFR 30-60 mL/min/1.73m²), no adjustment to the starting dose of Entresto is needed, but for those with severe renal impairment (eGFR <30 mL/min/1.73m²), the starting dose should be reduced to 24/26 mg twice daily. 1

Renal Function Assessment and Monitoring

When initiating or titrating Entresto in patients with renal impairment:

• Assess baseline renal function before starting therapy
• Monitor renal function within 1-2 weeks after initiation or dose increase 1
• Continue monitoring monthly for the first 3 months, then every 3 months thereafter 1
• Pay special attention to serum potassium levels, particularly in patients with:
  • Severe renal impairment
  • Diabetes
  • Hypoaldosteronism
  • High potassium diet 2

Dosing Recommendations Based on Renal Function

1. Moderate renal impairment (eGFR 30-60 mL/min/1.73m²):

   • Standard initial dosing can be used
   • No adjustment needed to starting dose 1

2. Severe renal impairment (eGFR <30 mL/min/1.73m²):

   • Reduce starting dose to 24/26 mg twice daily 1, 2
   • Titrate cautiously based on tolerability

Managing Changes in Renal Function

If a patient experiences worsening renal function while on Entresto:

• A decrease in eGFR of >30% should alert clinicians that dose reduction may be necessary 1
• However, short-term changes in eGFR during initiation do not necessarily predict longer-term adverse outcomes 1
• Recent evidence from a 2024 study suggests that patients experiencing deterioration of kidney function to eGFR <30 mL/min/1.73m² may still benefit from continuation of sacubitril/valsartan with no incremental safety risk 3

Managing Potential Complications

Hyperkalemia

• Monitor serum potassium periodically, especially in high-risk patients 2
• If hyperkalemia occurs:
  • Consider reducing the dose of Entresto
  • Provide education regarding low potassium diet
  • Consider potassium binders in selected cases, though more data are needed regarding their use in heart failure patients 1

Hypotension

• Correct volume or salt depletion prior to administration 2
• If hypotension occurs:
  • Consider adjusting diuretic doses
  • Evaluate and treat other causes of hypotension (e.g., hypovolemia)
  • If persistent, reduce Entresto dosage or temporarily discontinue 2

Clinical Pearls and Caveats

• Entresto works through inhibition of the renin-angiotensin-aldosterone system (RAAS), which can affect renal function in susceptible individuals 2
• Pharmacokinetic studies show that while renal impairment doesn't impact sacubitril and valsartan exposure, it does increase exposure to sacubitrilat (the active neprilysin inhibitor) 4
• Long-term sacubitril/valsartan therapy has been associated with renal protection in patients with heart failure with reduced ejection fraction 5
• In patients with bilateral or unilateral renal artery stenosis, Entresto may increase blood urea and serum creatinine levels - monitor renal function closely in these patients 2

Algorithm for Managing Entresto in Renal Impairment

1. Assess baseline renal function
2. Determine appropriate starting dose:
   • eGFR ≥30 mL/min/1.73m²: Standard starting dose
   • eGFR <30 mL/min/1.73m²: Reduced dose (24/26 mg twice daily)
3. Monitor renal function and electrolytes:
   • 1-2 weeks after initiation/dose change
   • Monthly for first 3 months
   • Every 3 months thereafter
4. If worsening renal function occurs:
   • eGFR decrease >30%: Consider dose reduction
   • Evaluate volume status and adjust diuretics if needed
   • Do not discontinue therapy based solely on mild, transient changes in renal function
5. If hyperkalemia occurs:
   • Consider dose reduction
   • Dietary counseling
   • Evaluate concomitant medications

Recent evidence suggests that even patients who experience deterioration to eGFR <30 mL/min/1.73m² may continue to benefit from Entresto therapy with appropriate monitoring and dose adjustment.