Until what glomerular filtration rate (GFR) can sacubitril valsartan be used?

Sacubitril/Valsartan Use Based on GFR Thresholds in Heart Failure

Sacubitril/valsartan can be initiated in patients with eGFR ≥30 mL/min/1.73 m² at standard doses, and at reduced doses for patients with severe renal impairment (eGFR <30 mL/min/1.73 m²). 1, 2

Dosing Recommendations Based on Renal Function

For eGFR ≥30 mL/min/1.73 m²:

• No starting dose adjustment required for mild-to-moderate renal impairment 2, 3
• Standard initiation protocol can be followed with target maintenance dose of 97/103 mg twice daily 2

For eGFR <30 mL/min/1.73 m² (Severe Renal Impairment):

• Reduce starting dose to 24/26 mg twice daily 2, 1
• Gradually double the dose every 2-4 weeks to target maintenance dose of 97/103 mg twice daily, as tolerated 2, 1
• Close monitoring of renal function, electrolytes, and blood pressure is essential 2

Evidence Supporting Use in Renal Impairment

• Recent data from clinical studies suggest that continuation of sacubitril/valsartan is associated with persistent clinical benefit even when eGFR declines below 30 mL/min/1.73 m² 4
• In the TRANSITION study, patients with renal dysfunction (eGFR ≥30 to <60 mL/min/1.73 m²) showed significant improvements in eGFR after sacubitril/valsartan initiation 5
• A meta-analysis demonstrated that sacubitril/valsartan significantly increased eGFR compared to RAS inhibitors in patients with heart failure and CKD 6

Clinical Considerations and Monitoring

• Patients with eGFR <30 mL/min/1.73 m² were excluded from the PARADIGM-HF trial, creating an evidence gap for this population 2, 3

• Patients with severe renal impairment have higher rates of:

  • Hyperkalemia (16.3% vs 6.5% in those with normal renal function) 5
  • Renal impairment events (6.4% vs 2.1%) 5
  • 30-day readmission rates (37% vs 9.3%) 2

• Monitor for:

  • Blood pressure (maintain systolic BP >100 mmHg) 2, 3
  • Serum potassium levels 2, 3
  • Renal function 2, 1

Emerging Evidence

• A 2024 post-hoc analysis of PARADIGM-HF and PARAGON-HF trials found that continuation of sacubitril/valsartan in patients whose eGFR deteriorated to <30 mL/min/1.73 m² was associated with persistent clinical benefit without incremental safety risks 4
• A small study of 66 CKD patients found that sacubitril/valsartan was safe in CKD, offering stability in CKD progression after 6 months 7

Practical Algorithm for Decision Making

1. Determine patient's current eGFR
2. For eGFR ≥30 mL/min/1.73 m²:
   • Start standard dose (49/51 mg twice daily)
   • Titrate to target dose of 97/103 mg twice daily as tolerated 2, 3
3. For eGFR <30 mL/min/1.73 m²:
   • Start reduced dose (24/26 mg twice daily)
   • Titrate slowly (every 2-4 weeks) to target dose if tolerated 2, 1
   • Monitor more frequently for adverse effects 5
4. For patients already on sacubitril/valsartan whose eGFR declines below 30 mL/min/1.73 m²:
   • Recent evidence supports continuation with appropriate monitoring 4
   • Consider dose reduction if adverse effects occur 1