What are the dosing adjustments for sacubitril (Angiotensin Receptor-Neprilysin Inhibitor) valsartan in patients with Chronic Kidney Disease (CKD)?

Sacubitril/Valsartan Dosing Adjustments in Chronic Kidney Disease

For patients with chronic kidney disease (CKD), the starting dose of sacubitril/valsartan should be reduced to 24/26 mg twice daily when eGFR is less than 30 mL/min/1.73 m².1, 2

Dosing Recommendations Based on Renal Function

• For patients with normal to moderate renal impairment (eGFR ≥30 mL/min/1.73 m²):

  • Standard starting dose: 49/51 mg twice daily 1
  • Target maintenance dose: 97/103 mg twice daily 1
  • No specific dose adjustment needed 2

• For patients with severe renal impairment (eGFR <30 mL/min/1.73 m²):

  • Reduced starting dose: 24/26 mg twice daily 2, 1
  • Titrate cautiously based on clinical response 1

Monitoring Recommendations

• Check renal function and potassium within 1-2 weeks after initiation or dose increase 2
• Monitor for symptomatic hypotension, as it is more common with sacubitril/valsartan than with valsartan alone 2
• Continue monitoring renal function and potassium at least monthly for the first 3 months and every 3 months thereafter 2

Clinical Considerations

• Sacubitril/valsartan appears to be safe in CKD patients and may offer stability in CKD progression after 6 months of treatment 3
• Meta-analyses suggest sacubitril/valsartan may actually improve renal function in CKD patients compared to ACEIs/ARBs alone, with studies showing:
  • Increased eGFR (MD = 1.90,95% CI 0.30-3.50) 4
  • Reduced incidence of serum creatinine elevation (OR: 0.79,95% CI 0.67-0.95) 5
  • Slower decline of eGFR compared to control groups 6

Cautions and Potential Adverse Effects

• Be vigilant for hypotension, which occurs more frequently with sacubitril/valsartan (OR: 1.71,95% CI 1.15-2.56) 5
• Monitor for hyperkalemia, although the risk appears similar to ACEIs/ARBs 5
• Consider reducing the dose or discontinuing therapy in cases of:
  • Symptomatic hypotension 2
  • Uncontrolled hyperkalemia despite medical treatment 2
  • Serum creatinine rise >30% within 4 weeks of initiation or dose increase 2

Titration Protocol

• Start with the appropriate dose based on renal function
• Adjust doses every 2-4 weeks as tolerated by the patient 1
• Target the maintenance dose of 97/103 mg twice daily if tolerated, even in patients with CKD 1
• If intolerance develops (hypotension, hyperkalemia, worsening renal function), consider dose reduction rather than discontinuation 2

Additional Benefits in CKD Patients

• Sacubitril/valsartan has shown cardiovascular benefits in CKD patients, including:
  • Reduced risk of cardiovascular death or heart failure hospitalization (OR: 0.68,95% CI 0.61-0.76) 5
  • Decreased levels of cardiac biomarkers (troponin I and NT-proBNP) by 16% and 18% respectively 7
  • Improved left ventricular ejection fraction 3

The evidence suggests that sacubitril/valsartan can be safely used in patients with CKD with appropriate dose adjustments, and may offer both cardiovascular and renal benefits beyond those of traditional ACEIs/ARBs.