Can apixaban (Elaquis) be used in patients with severe renal impairment on dialysis?

Can Apixaban (Eliquis) Be Used in Dialysis Patients?

Yes, apixaban can be used in dialysis patients, and it may be preferable to warfarin based on current evidence, though the optimal dosing remains debated between standard-dose (5 mg twice daily) and reduced-dose (2.5 mg twice daily) regimens.

FDA Approval and Dosing Guidance

• The FDA has approved apixaban for use in end-stage renal disease (ESRD) patients on dialysis at the standard dose of 5 mg twice daily, though this approval is based primarily on pharmacokinetic data rather than clinical outcome trials 1
• The FDA label explicitly states "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" 1
• Dose reduction to 2.5 mg twice daily is recommended if the patient meets at least two of the following criteria: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL 1, 2

Guideline Recommendations

American Heart Association/American College of Cardiology/Heart Rhythm Society (2019)

• The AHA/ACC/HRS guidelines state that "use of warfarin or apixaban might be reasonable in dialysis-dependent patients with AF, but further study is warranted" 3
• This represents a soft recommendation acknowledging the limited evidence base 3

CHEST Guidelines (2018)

• In end-stage renal disease (CrCl <15 mL/min or dialysis-dependent), CHEST recommends individualized decision-making and suggests NOACs should generally not be used 3
• However, they note that in the USA, apixaban 5 mg twice daily is approved for use in AF patients receiving hemodialysis 3
• They recommend well-managed warfarin (TTR >65-70%) as the preferred option if anticoagulation is chosen 3

NCCN Guidelines (2018)

• The NCCN Panel explicitly states there are insufficient data to support safe apixaban dosing in stage IV chronic kidney disease patients, especially those on hemodialysis 3
• Apixaban is listed as contraindicated when CrCl <25 mL/min 3

Pharmacokinetic Rationale

• Apixaban has the lowest renal clearance (27%) among all direct oral anticoagulants, making it theoretically the most suitable NOAC for severe renal impairment 3, 2
• Pharmacokinetic studies show that 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 3, 2, 4
• Dialysis has limited impact on apixaban clearance, removing only a small fraction of the drug 3

Clinical Evidence: Apixaban vs Warfarin

Observational Data Supporting Apixaban

• A large US Renal Data System study of 25,523 patients (2,351 on apixaban, 23,172 on warfarin) found that standard-dose apixaban (5 mg twice daily) was associated with lower risk of stroke/embolism, death, and major bleeding compared to both reduced-dose apixaban (2.5 mg twice daily) and warfarin 3, 2
• A meta-analysis of 43,850 patients found apixaban was associated with lower risk of major bleeding compared with warfarin, with no excess risk of thromboembolic events 3
• Multiple retrospective cohort studies demonstrate equivalent efficacy for stroke prevention with superior or equivalent safety profiles compared to warfarin 5, 6, 7

Warfarin Concerns in Dialysis Patients

• Warfarin carries a markedly increased bleeding risk in ESRD patients and may cause calciphylaxis, a painful and often lethal condition caused by calcification and occlusion of cutaneous arteries 2, 4
• Recent meta-analyses show warfarin did not reduce deaths, ischemic events, or strokes but increased the incidence of major bleeding in dialysis patients 3, 2

Critical Dosing Controversy

The Standard-Dose (5 mg) vs Reduced-Dose (2.5 mg) Debate

• Pharmacokinetic data show that 5 mg twice daily produces supratherapeutic levels in dialysis patients, while 2.5 mg twice daily produces exposure similar to standard dosing in patients with normal renal function 2, 4
• However, the largest observational study found that standard-dose apixaban (5 mg) had better outcomes than reduced-dose (2.5 mg) in dialysis patients 3, 2
• The American College of Cardiology recommends 5 mg twice daily for stable hemodialysis patients, with reduction to 2.5 mg twice daily only if age ≥80 years OR weight ≤60 kg 2

Practical Clinical Approach

When to Use Apixaban in Dialysis Patients

1. Consider apixaban as a reasonable alternative to warfarin in dialysis patients requiring anticoagulation for atrial fibrillation or venous thromboembolism 3, 7
2. Apixaban is preferable to other NOACs (dabigatran, rivaroxaban, edoxaban) due to its lowest renal clearance 3
3. Edoxaban is absolutely contraindicated in dialysis patients and should never be used 2

Recommended Dosing Strategy

• Start with 5 mg twice daily for most dialysis patients, as this is the FDA-approved dose and has the best observational outcomes data 2, 1
• Reduce to 2.5 mg twice daily if the patient meets at least two of: age ≥80 years, weight ≤60 kg, or serum creatinine ≥1.5 mg/dL 2, 1
• Consider 2.5 mg twice daily in patients at particularly high bleeding risk, though recognize this may reduce efficacy 2

Important Caveats and Monitoring

• Avoid concomitant use of dual P-glycoprotein and strong CYP3A4 inhibitors or inducers, as these significantly alter apixaban levels 3, 4
• Avoid concomitant antiplatelet therapy (including low-dose aspirin) as this substantially elevates bleeding risk 3
• Anti-factor Xa monitoring is not routinely recommended but may be considered in high-risk situations, though therapeutic ranges are not well-established 8
• One case report documented gastrointestinal bleeding with apixaban 2.5 mg twice daily in a dialysis patient, with anti-factor Xa levels exceeding the upper limit of detection 8

Alternative to Anticoagulation

• Left atrial appendage occlusion (LAAO) should be considered as an alternative to anticoagulation in dialysis patients at high risk of both stroke and bleeding 3
• This mechanical approach avoids the bleeding risks associated with all anticoagulants 3

Bottom Line

Apixaban is a reasonable and potentially superior alternative to warfarin in dialysis patients, with the standard dose of 5 mg twice daily supported by the largest observational dataset, though dose reduction to 2.5 mg twice daily should be considered in elderly, low-weight patients or those at particularly high bleeding risk 3, 2, 1. The evidence base remains limited by the absence of randomized controlled trials, but observational data consistently favor apixaban over warfarin for both safety and efficacy 3, 7.