What is the recommended dose of apixaban (a direct oral anticoagulant) for patients with End-Stage Renal Disease (ESRD) undergoing dialysis?

Apixaban Dosing in ESRD with Dialysis

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

Evidence Supporting Apixaban Use in ESRD

• Apixaban has the lowest renal clearance (27%) among direct oral anticoagulants (DOACs), making it potentially more suitable for patients with severe renal impairment 1, 2
• Only about 4% of apixaban is removed during dialysis, making it a suitable option for patients on hemodialysis 2
• Pharmacokinetic studies show that ESRD results in a modest increase (36%) in apixaban AUC and no increase in Cmax, with hemodialysis having limited impact on apixaban clearance 3
• In dialysis patients, apixaban 2.5 mg twice daily results in drug exposure comparable to the standard 5 mg twice daily dose in patients with normal renal function 4

Safety and Efficacy Compared to Warfarin

• Recent studies demonstrate that apixaban is associated with:
  • Lower risk of major bleeding compared to warfarin in ESRD patients (pooled odds ratio 0.27; 95% CI, 0.07-0.95) 5
  • Fewer overall bleeding events than warfarin (18.9% vs 42.0%; P = .01) 6
  • Reduced risk of major and clinically relevant non-major bleeding (RR 0.69,95% CI 0.57-0.84, p = 0.0002) 7
• Standard-dose apixaban (5 mg twice daily) has been associated with lower risk of stroke/embolism than low-dose apixaban (2.5 mg) and warfarin in dialysis-dependent patients 4

Dosing Algorithm for Apixaban in ESRD

1. Standard dosing: 5 mg twice daily for most ESRD patients on dialysis 4, 1
2. Reduced dosing: 2.5 mg twice daily if patient meets ANY of these criteria:
   • Age ≥80 years 4, 1
   • Body weight ≤60 kg 4, 1
   • Concomitant use of dual P-glycoprotein and strong CYP3A4 inhibitors 1

Important Considerations

• The American College of Cardiology and American Heart Association/American College of Cardiology/Heart Rhythm Society (AHA/ACC/HRS) guidelines support apixaban use in ESRD patients on dialysis 1, 2
• While the European Heart Rhythm Association has historically been more cautious about routine NOAC use in severe renal dysfunction, apixaban is increasingly recognized as a viable option 1, 2
• Warfarin remains an alternative but is associated with higher bleeding risk and potential for calciphylaxis in ESRD patients 1, 6, 7

Common Pitfalls and Caveats

• Avoid using other DOACs in ESRD:
  • Edoxaban is 50% renally excreted and not recommended in patients with end-stage renal disease or on dialysis 4, 2
  • Dabigatran and rivaroxaban have been associated with higher risk of hospitalization or death from bleeding compared to warfarin in dialysis patients 4
• Regular monitoring for bleeding complications is essential throughout the duration of therapy 8
• Drug interactions should be carefully assessed, particularly with medications that affect P-glycoprotein and CYP3A4 pathways 1