Can I use sacubitril-valsartan (Angiotensin Receptor-Neprilysin Inhibitor) in patients with impaired renal function?

Use of Sacubitril-Valsartan in Renal Failure

Sacubitril-valsartan can be used in patients with renal failure, including severe renal impairment (eGFR <30 mL/min/1.73 m²), but requires dose adjustment and careful monitoring. 1

Dosing Recommendations Based on Renal Function

For Patients with Renal Impairment:

• Mild to moderate renal impairment (eGFR 30-59 mL/min/1.73 m²):

  • No starting dose adjustment required
  • Standard starting dose: 49/51 mg twice daily
  • Target dose: 97/103 mg twice daily

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

  • Reduced starting dose: 24/26 mg twice daily
  • Titrate dose every 2-4 weeks as tolerated
  • Target maintenance dose: 97/103 mg twice daily 1, 2

Monitoring Requirements

When initiating or titrating sacubitril-valsartan in patients with renal impairment:

1. Blood pressure monitoring: Assess for hypotension, especially in patients with volume depletion
2. Renal function: Monitor serum creatinine within 1-2 weeks after initiation and with each dose increase
3. Electrolytes: Check potassium levels regularly, especially in patients with severe renal impairment 3

Evidence Supporting Use in Renal Impairment

Recent evidence supports the continued use of sacubitril-valsartan even when renal function deteriorates:

• A 2024 post-hoc analysis of PARADIGM-HF and PARAGON-HF trials found that patients who experienced deterioration of kidney function to eGFR <30 mL/min/1.73 m² still benefited from sacubitril-valsartan with no incremental safety risk compared to ACE inhibitors or ARBs 4

• A 2023 study demonstrated that moderate eGFR decline when transitioning from RAS inhibitors to sacubitril-valsartan is not consistently associated with adverse outcomes, and the long-term benefits are retained across a broad range of eGFR declines 5

• A meta-analysis showed that sacubitril-valsartan may have renal protective effects compared to RAS inhibitors alone, with significant increases in eGFR in patients with heart failure and chronic kidney disease 6

Cautions and Contraindications

Despite the evidence supporting use in renal impairment, be aware of these important precautions:

• Hypotension risk: Patients with renal impairment are at higher risk for hypotension; correct volume depletion before initiating therapy 3

• Hyperkalemia risk: Monitor potassium levels closely, especially in patients with severe renal impairment 3

• Contraindications: Do not use in patients with history of angioedema with ACE inhibitors or ARBs, during pregnancy, with severe hepatic impairment, or concomitantly with aliskiren in diabetic patients 3

Clinical Approach Algorithm

1. Assess baseline renal function:

   • Determine eGFR before initiating therapy

2. Select appropriate starting dose:

   • eGFR ≥30 mL/min/1.73 m²: Start with 49/51 mg twice daily
   • eGFR <30 mL/min/1.73 m²: Start with 24/26 mg twice daily

3. Monitor closely after initiation:

   • Check blood pressure, renal function, and potassium within 1-2 weeks

4. Titrate dose gradually:

   • Increase dose every 2-4 weeks as tolerated
   • Target dose: 97/103 mg twice daily for all patients if tolerated

5. Manage adverse effects:

   • If hypotension occurs: Consider adjusting diuretic doses
   • If renal function worsens: Temporary dose reduction may be needed, but do not discontinue therapy based solely on moderate eGFR decline 5

Common Pitfalls to Avoid

1. Discontinuing therapy prematurely: Early eGFR changes should not deter continuation of sacubitril-valsartan or stall uptitration 5

2. Inadequate monitoring: Failure to check renal function and potassium after initiation can lead to complications

3. Not adjusting concomitant medications: Diuretic doses may need adjustment when initiating sacubitril-valsartan to prevent hypotension

4. Overlooking drug interactions: Avoid concomitant use with ACE inhibitors (wait 36 hours after last ACE inhibitor dose before starting sacubitril-valsartan) 1