From the Guidelines
Apixaban can be used with caution in patients with end-stage renal disease (ESRD), but dose adjustment is necessary, with a recommended dose of 2.5 mg twice daily for ESRD patients on dialysis. This recommendation is based on pharmacokinetic data showing increased drug exposure in patients with severe renal impairment, as noted in the study by 1. While apixaban has relatively less renal clearance compared to other direct oral anticoagulants (about 27% renal elimination), drug accumulation can still occur in ESRD.
Some key points to consider when using apixaban in ESRD patients include:
- Monitoring patients closely for bleeding complications, as the risk of major bleeding is increased in patients with ESRD, as seen in the study by 1
- Considering regular assessment of anti-Factor Xa activity if available, to minimize the risk of bleeding complications
- Evaluating drug interactions, particularly with strong inhibitors of both CYP3A4 and P-glycoprotein, as these may further increase bleeding risk, as noted in the study by 1
- Individualizing the decision to use apixaban in ESRD, weighing the thrombotic risk against bleeding risk, and considering patient preferences and adherence factors, as recommended in the guideline by 1
It is also important to note that the European Medical Agency has not yet conformed to the FDA's approach to dosing apixaban in ESRD patients, and that the use of apixaban in this population is not without controversy, as discussed in the study by 1. However, based on the available evidence, apixaban can be a viable option for ESRD patients who require anticoagulation, as long as the necessary precautions are taken to minimize the risk of bleeding complications.
From the FDA Drug Label
Patients with End-Stage Renal Disease on Dialysis Clinical efficacy and safety studies with apixaban did not enroll patients with end-stage renal disease (ESRD) on dialysis. In patients with ESRD maintained on intermittent hemodialysis, administration of apixaban at the usually recommended dose [see Dosage and Administration (2. 1)] will result in concentrations of apixaban and pharmacodynamic activity similar to those observed in the ARISTOTLE study [see Clinical Pharmacology (12. 3)]. It is not known whether these concentrations will lead to similar stroke reduction and bleeding risk in patients with ESRD on dialysis as was seen in ARISTOTLE No dose adjustment is recommended for patients with renal impairment, including those with ESRD on dialysis [see Dosage and Administration (2. 1)].
Apixaban can be given to patients with ESRD, however, caution is advised as clinical efficacy and safety studies did not enroll patients with ESRD on dialysis, and it is not known whether the concentrations of apixaban will lead to similar stroke reduction and bleeding risk in patients with ESRD on dialysis as was seen in other studies 2.
From the Research
Apixaban Use in ESRD Patients
- Apixaban can be given to patients with End-Stage Renal Disease (ESRD), as several studies suggest its safety and efficacy in this population 3, 4, 5, 6.
- A review of literature reveals substantial evidence supporting the safety and effectiveness of apixaban in ESRD patients, with some studies indicating a lower prevalence of bleeding and thromboembolic events compared to warfarin therapy 3.
- Meta-analyses have shown that apixaban is associated with a reduced risk of major bleeding compared to warfarin in ESRD patients, with a pooled odds ratio of 0.42 (95% CI: 0.28-0.61) 4 and 0.53 (95% CI: 0.45-0.64) 6.
- Apixaban may be a cautious consideration in hemodialysis patients, with similar rates of clinically relevant nonmajor bleeding events and minor bleeding events compared to warfarin 5.
- A systematic review and meta-analysis found that apixaban had an overall favorable risk-benefit profile, with significant reductions in ischemic stroke, major bleeding, and intracranial bleeding compared to warfarin in ESRD patients on hemodialysis with non-valvular atrial fibrillation and/or venous thromboembolism 6.
Dosage and Monitoring
- The package insert for apixaban does not provide specific guidance for use in ESRD patients, and current dosing recommendations are based largely on a single-dose pharmacokinetic study of eight patients 7.
- A case report describes the use of apixaban 2.5 mg twice/day in a patient with ESRD requiring hemodialysis, with antifactor Xa monitoring used to assess apixaban concentrations 7.
- Further pharmacokinetic and clinical data are likely necessary to better characterize apixaban use in ESRD patients and optimize safety and efficacy 7, 4.