What is the recommended dose of apixaban (apixaban) for patients with End-Stage Renal Disease (ESRD)?

Apixaban Dosing in End-Stage Renal Disease (ESRD)

For patients with end-stage renal disease (ESRD) on hemodialysis, apixaban 5 mg twice daily is the FDA-approved dose, with reduction to 2.5 mg twice daily if the patient is ≥80 years or weighs ≤60 kg. 1, 2

Dosing Recommendations

• In the United States, apixaban 5 mg twice daily is approved for use in chronic, stable dialysis-dependent patients 2
• Dose reduction to 2.5 mg twice daily is recommended if the patient meets at least one of these criteria:
  • Age ≥80 years 2, 1
  • Body weight ≤60 kg 2, 1
• Pharmacokinetic studies show that apixaban 5 mg twice daily in ESRD patients on dialysis produces drug exposure similar to that observed in the ARISTOTLE study 1
• Apixaban has the lowest renal clearance (27%) among NOACs, making it potentially preferable in patients with severe renal impairment 2, 1

Evidence Supporting Use in ESRD

• The FDA approval for apixaban in ESRD is based primarily on pharmacokinetic data rather than clinical outcome trials 3
• Studies have shown that compared to warfarin, apixaban is associated with:
  • Reduced risk of major bleeding (pooled odds ratio 0.42; 95% CI, 0.28-0.61) 4
  • In dialysis patients specifically, the pooled odds ratio for major bleeding was 0.27 (95% CI, 0.07-0.95) 4
  • No significant difference in thromboembolic events (pooled odds ratio 0.56; 95% CI, 0.23-1.39) 4

Regional Differences in Recommendations

• European guidelines are more conservative and generally do not recommend routine use of NOACs, including apixaban, in patients with CrCl <15 mL/min or on dialysis 2
• American guidelines (AHA/ACC/HRS) recommend apixaban for ESRD patients on dialysis 2

Safety Considerations

• Hemodialysis has limited impact on apixaban clearance, reducing concentrations by only about 14% 5
• Concomitant use of dual P-glycoprotein and strong CYP3A4 inducers or inhibitors may require dosing adjustment or avoidance in patients with ESRD 2
• Monitoring for bleeding complications is essential throughout therapy 6
• Rare cases of extremely elevated INR have been reported with apixaban in ESRD patients, though INR monitoring is not recommended for routine management 7

Alternative Anticoagulation Options

• For ESRD patients, vitamin K antagonists (warfarin) are an alternative if well-managed with TTR >65-70% 3
• However, warfarin use in ESRD is associated with increased bleeding risk and rarely may result in calciphylaxis 2

Clinical Decision Algorithm

1. Confirm need for anticoagulation in ESRD patient
2. Assess patient characteristics:
   • If patient is ≥80 years OR weighs ≤60 kg → Use apixaban 2.5 mg twice daily 2, 1
   • If neither criterion is met → Use apixaban 5 mg twice daily 2, 1
3. Monitor for bleeding complications and thromboembolic events 6
4. Consider warfarin as an alternative only if good anticoagulation control (TTR >65-70%) can be maintained 3