Do you use a reduced dose of Eliquis (apixaban) in patients with impaired renal function on dialysis?

Reduced Dose Apixaban in Dialysis Patients

For patients on dialysis with atrial fibrillation, apixaban 2.5 mg twice daily is the preferred NOAC dosing regimen, as it results in drug exposure comparable to standard dosing in patients with normal renal function while avoiding supratherapeutic levels. 1

Dosing Recommendations for Dialysis Patients

• In the United States, apixaban 2.5 mg twice daily is approved for use in chronic, stable dialysis-dependent patients 2
• The standard 5 mg twice daily dose of apixaban leads to supratherapeutic levels in dialysis patients and should be avoided 1
• Pharmacokinetic studies show that apixaban 2.5 mg twice daily in hemodialysis patients results in drug exposure similar to the standard 5 mg twice daily dose in patients with normal renal function 1
• Only about 4% of apixaban is removed during dialysis, making it a suitable option for patients on hemodialysis 2, 1

Evidence Supporting Apixaban in Dialysis

• Apixaban is the least renally cleared NOAC (27% renal clearance) compared to edoxaban (50%) and rivaroxaban (33%), making it potentially more suitable for patients with severe renal impairment 2
• Retrospective studies suggest apixaban may be associated with a lower risk of major bleeding compared to warfarin in dialysis patients 3, 4
• The 2018 European Heart Rhythm Association practical guide notes that apixaban may be preferable in patients with severe renal impairment due to its lower renal clearance and demonstrated relative safety versus warfarin as renal function decreases 2

Cautions and Limitations

• The 2014 AHA/ACC/HRS guidelines had no specific recommendation for apixaban in end-stage CKD on dialysis, though this has evolved with newer evidence 2
• The RENAL-AF trial, which compared apixaban to warfarin in hemodialysis patients, was stopped prematurely due to enrollment challenges and had inadequate power to draw definitive conclusions about bleeding rates 5
• A retrospective cohort study found that compared to no anticoagulation, apixaban was associated with a higher incidence of fatal or intracranial bleeding in dialysis patients, particularly with the 5 mg twice daily dose 6
• The efficacy and safety of NOACs in patients with end-stage renal dysfunction remains subject to ongoing studies, and the routine use in severe renal dysfunction is still being established 2

Practical Approach to Anticoagulation in Dialysis Patients

• For patients requiring anticoagulation on dialysis, consider these options in order of preference:

  1. Apixaban 2.5 mg twice daily (if available and approved in your region) 2, 1
  2. Warfarin with close INR monitoring (target INR 2.0-3.0) 2
  3. Other NOACs are generally not recommended in dialysis patients 2

• When using apixaban in dialysis patients:

  • Monitor for bleeding complications closely 5
  • Be aware that bleeding events are approximately 10-fold more frequent than stroke or systemic embolism in this high-risk population 5
  • Consider patient-specific factors such as bleeding history, concomitant medications, and stability on dialysis 2

• For patients with both high bleeding and stroke risk, consider left atrial appendage occlusion as an alternative to anticoagulation 2

The decision to use anticoagulation in dialysis patients requires careful consideration of risks and benefits, as this population has both high bleeding and thrombotic risk. While evidence continues to evolve, apixaban 2.5 mg twice daily appears to be the most reasonable NOAC option when anticoagulation is indicated in dialysis patients.