What are the guidelines for using apixaban (eliquis) in patients with end-stage renal failure (ESRF)?

Guidelines for Apixaban Use in End-Stage Renal Failure (ESRF)

In patients with end-stage renal failure (ESRF), apixaban 2.5 mg twice daily is the preferred NOAC option when anticoagulation is required, as it has the lowest renal clearance (27%) among DOACs and demonstrates better safety compared to warfarin in this population. 1

Apixaban in ESRF: Current Guideline Recommendations

• The European Heart Rhythm Association (EHRA) does not recommend routine use of NOACs, including apixaban, in patients with severe renal dysfunction (CrCl <15 mL/min) or on dialysis due to limited evidence from hard endpoint studies 1
• In the United States (but not in Europe), apixaban 5 mg twice daily is approved for use in chronic, stable dialysis-dependent patients, though plasma levels at this dose were shown to be supratherapeutic 1
• The American College of Cardiology recommends apixaban 5 mg twice daily for ESRD patients on stable hemodialysis, with dose reduction to 2.5 mg twice daily if the patient is ≥80 years or weighs ≤60 kg 2
• The American Heart Association/American College of Cardiology/Heart Rhythm Society (AHA/ACC/HRS) guidelines recommend apixaban 5 mg or 2.5 mg twice daily for patients with CrCl <15 mL/min or on dialysis 1

Dosing Recommendations

• For patients with ESRF on dialysis, apixaban 2.5 mg twice daily is recommended based on pharmacokinetic studies showing this dose in dialysis patients produces drug exposure similar to the standard dose in patients with normal renal function 1, 2, 3
• Dose reduction to 2.5 mg twice daily is indicated if the patient has at least two of the following: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL 2, 4
• The FDA label states that for patients with ESRD on dialysis, no dose adjustment is required for prophylaxis of DVT following hip/knee replacement surgery or for treatment of DVT/PE 4

Evidence Supporting Apixaban Use in ESRF

• Meta-analyses have shown that apixaban is associated with a significantly reduced risk of major bleeding compared to warfarin in ESRD patients (pooled odds ratio 0.42; 95% CI, 0.28-0.61) 5
• In dialysis-dependent ESRD patients specifically, the pooled odds ratio for major bleeding was 0.27 (95% CI, 0.07-0.95) favoring apixaban over warfarin 5
• Recent meta-analysis of ten studies including 6,693 ESRD patients on apixaban and 19,836 on warfarin found a risk ratio for major bleeding of 0.69 (95% CI 0.57-0.84) in favor of apixaban 6
• The risk of thromboembolic events appears similar between apixaban and warfarin in ESRD patients (pooled OR, 0.56; 95% CI, 0.23-1.39) 5

Safety Considerations and Monitoring

• Major bleeding events occurred in 15.2% of ESRD patients on apixaban in a recent observational study, with minor bleeding more common (36.4%) 7
• BMI was identified as an independent risk factor for bleeding in ESRD patients on apixaban (OR = 0.9,95% CI: 0.8-0.99) 7
• Apixaban can cause elevation in INR values, with rare cases of extreme elevation reported in ESRD patients on hemodialysis 3
• Regular monitoring of renal function is recommended before initiation and at least annually thereafter 2

Practical Considerations

• Apixaban has the lowest renal clearance (27%) among NOACs, making it potentially preferable in patients with severe renal impairment 1
• Concomitant use of dual P-glycoprotein and strong CYP3A4 inducers or inhibitors may require dosing adjustment or avoidance in patients with ESRD 2
• The decision to anticoagulate ESRD patients should consider the increased bleeding risk present in this population with all anticoagulants 1, 2
• Creatinine clearance should be calculated using the Cockcroft-Gault method for accurate dosing decisions 1, 2

Warfarin Considerations in ESRF

• Observational studies have shown conflicting results for vitamin K antagonists (VKAs) in severe renal dysfunction 1
• While warfarin may reduce stroke and embolism in ESRD patients, it is associated with a markedly increased bleeding risk 1
• Warfarin use in ESRD may rarely result in calciphylaxis, a painful and often lethal condition caused by calcification and occlusion of cutaneous arteries 1
• The only registry assessing net benefit found no changes in overall mortality for warfarin in dialysis-dependent patients 1