What is the recommended dose of apixaban (Eliquis) or edoxaban (Savaysa) for a patient with impaired renal function undergoing haemodialysis (hemodialysis)?

Apixaban or Edoxaban in Haemodialysis Patients

For haemodialysis patients requiring anticoagulation, apixaban 5 mg twice daily is the recommended dose, with dose reduction to 2.5 mg twice daily only if the patient is ≥80 years old OR weighs ≤60 kg (not both required). Edoxaban is contraindicated in patients on dialysis and should not be used. 1

Apixaban Dosing in Haemodialysis

Standard Dosing Approach

The FDA-approved dose for haemodialysis patients is apixaban 5 mg twice daily, which produces drug exposure similar to that seen in the ARISTOTLE trial. 2 The American College of Cardiology and AHA/ACC/HRS guidelines support this dosing strategy. 3

• Dose reduction to 2.5 mg twice daily is indicated if the patient meets at least one of these criteria: 3

  • Age ≥80 years
  • Body weight ≤60 kg

• This differs from the atrial fibrillation dosing criteria in patients with normal renal function, where two of three criteria (age ≥80, weight ≤60 kg, or creatinine ≥1.5 mg/dL) are required for dose reduction. 2

Pharmacokinetic Evidence

The dosing recommendations are based on critical pharmacokinetic data showing that drug accumulation occurs in dialysis patients:

• Apixaban 2.5 mg twice daily in dialysis patients produces steady-state drug exposure comparable to 5 mg twice daily in patients with preserved renal function. 1, 4

• However, apixaban 5 mg twice daily in dialysis patients leads to supratherapeutic levels (area under the curve of 6045 ng h/ml) that exceed the 90th percentile for patients with normal renal function. 4

• Despite this accumulation, observational data from 25,523 patients in the US Renal Data System showed that standard-dose apixaban (5 mg twice daily) was associated with lower risk of stroke/embolism and death compared to reduced-dose apixaban (2.5 mg twice daily) and warfarin. 1

Clinical Trial Data

• The RENAL-AF trial (2022) randomized 154 haemodialysis patients to apixaban versus warfarin but stopped prematurely due to enrollment challenges. 5 The trial was underpowered but showed:
  • No significant difference in major or clinically relevant nonmajor bleeding between apixaban and warfarin (32% vs 26% at 1 year, HR 1.20,95% CI 0.63-2.30) 5
  • Similar stroke rates (3.0% vs 3.3%) 5
  • Bleeding events were approximately 10-fold more frequent than stroke in this population, highlighting the high bleeding risk regardless of anticoagulant choice. 5

Dialysis Impact on Drug Clearance

• Dialysis removes only 4% of apixaban, so timing of doses relative to dialysis sessions is not critical. 4
• Apixaban has the lowest renal clearance (27%) among NOACs, making it theoretically preferable in severe renal impairment. 3, 2

Edoxaban in Haemodialysis

Edoxaban is absolutely contraindicated in patients with end-stage renal disease or on dialysis and should never be used. 1

• Edoxaban is 50% renally excreted, leading to excessive drug accumulation in dialysis patients. 1
• The ENGAGE AF-TIMI 48 trial excluded patients with creatinine clearance <30 mL/min. 1
• No dosing recommendations exist for edoxaban in dialysis patients, and its use is explicitly not recommended by guidelines. 1

Critical Considerations and Pitfalls

Common Dosing Errors to Avoid

• Do not automatically use 2.5 mg twice daily in all dialysis patients—this is a common error. The majority of dialysis patients should receive 5 mg twice daily unless they meet specific age or weight criteria. 3

• Do not apply the atrial fibrillation dose-reduction criteria (requiring 2 of 3 factors) to dialysis patients. In dialysis, only one factor (age ≥80 OR weight ≤60 kg) is needed for dose reduction. 3

• Do not use edoxaban, dabigatran, or rivaroxaban in dialysis patients. Dabigatran and rivaroxaban have been associated with higher bleeding risk than warfarin in dialysis populations. 1

Bleeding Risk Management

• Major bleeding rates in dialysis patients on apixaban range from 7-14% in observational studies, substantially higher than in patients with preserved renal function. 6

• Monitor for bleeding complications closely, particularly gastrointestinal bleeding, which is common in this population. 7

• Drug interactions with dual P-glycoprotein and strong CYP3A4 inhibitors or inducers may require dose adjustment or avoidance. 3, 2

Alternative: Warfarin

If apixaban is not tolerated or contraindicated:

• Warfarin remains an alternative, though it carries increased bleeding risk and did not reduce deaths, ischemic events, or strokes in recent meta-analyses of dialysis patients. 1

• Warfarin may rarely cause calciphylaxis in ESRD patients, a painful and often lethal condition. 3

• Target INR 2.0-3.0, though time in therapeutic range is typically poor (44% in RENAL-AF). 5