What is the recommended dosing of apixaban (eliquis) for patients with impaired renal function (low eGFR)?

Apixaban Dosing in Low eGFR

For patients with atrial fibrillation and low eGFR, apixaban is the preferred direct oral anticoagulant, with dose reduction to 2.5 mg twice daily required when at least two of three criteria are met: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL. 1, 2

Dosing by Renal Function Stage

CKD Stage 3b (eGFR 30-44 mL/min)

• Standard dose: 5 mg twice daily 1
• Reduce to 2.5 mg twice daily only if patient meets ≥2 of the following: 1, 2
  • Age ≥80 years
  • Body weight ≤60 kg
  • Serum creatinine ≥1.5 mg/dL (133 μmol/L)
• This dosing is FDA-approved and supported by RCT data from ARISTOTLE 1, 3

CKD Stage 4 (eGFR 15-29 mL/min)

• Use reduced dose: 2.5 mg twice daily 1
• Both FDA and European Medicines Agency approve this reduced dose regimen 1
• Apixaban has the lowest renal clearance (27%) among all DOACs, making it the most favorable option in severe renal impairment 1
• Registry data shows apixaban reduces major bleeding by 50% compared to warfarin in this population (HR 0.50,95% CI 0.38-0.66) 3

CKD Stage 5 (eGFR <15 mL/min) and Dialysis

• For dialysis patients: 2.5 mg twice daily is recommended based on pharmacokinetic data 4
• The FDA approves apixaban 5 mg twice daily for chronic stable dialysis patients, but pharmacokinetic studies show this dose produces supratherapeutic levels 1
• Dose reduction to 2.5 mg twice daily in dialysis patients produces drug exposure similar to standard dosing in patients with normal renal function 4
• Meta-analysis of 43,850 patients shows apixaban associated with lower major bleeding risk versus warfarin with no excess thromboembolic events in ESRD 1

Why Apixaban Over Other Anticoagulants

Superiority in Renal Impairment

• Apixaban demonstrates the greatest bleeding risk reduction among all DOACs as renal function declines 3, 5
• In patients with eGFR 15-30 mL/min, apixaban shows 21% lower relative risk of major bleeding versus warfarin 5
• Apixaban reduces stroke/systemic embolism and mortality regardless of renal function, with consistent efficacy across all eGFR ranges 3

Comparison to Other DOACs

• Rivaroxaban (35% renal clearance) shows increased major bleeding risk in hemodialysis patients (RR 1.45-1.76) 1
• Dabigatran (80% renal clearance) is contraindicated in CrCl <30 mL/min in Europe; US approval of 75 mg twice daily is based only on pharmacokinetic simulations without clinical outcome data 1
• Edoxaban (50% renal clearance) requires dose reduction to 30 mg daily for CrCl 15-50 mL/min 1

Critical Monitoring Requirements

Renal Function Assessment

• Monitor kidney function regularly to allow appropriate dose adjustments 1
• Use Cockcroft-Gault equation for dosing decisions, as this was used in pivotal trials 1, 3
• Reassess renal function at least annually, or more frequently if clinical deterioration occurs 1

Common Pitfalls to Avoid

• Do not use standard 5 mg twice daily dosing in dialysis patients—this produces supratherapeutic levels 1, 4
• Avoid underdosing: only reduce dose when specific criteria are met 1
• Check for concomitant use of dual P-glycoprotein and strong CYP3A4 inhibitors/inducers, which may require dose adjustment 4, 2
• Warfarin carries risk of calciphylaxis in ESRD—a painful, often lethal condition from vascular calcification 1

Evidence Quality Considerations

The dosing recommendations for eGFR >30 mL/min are based on high-quality RCT data from ARISTOTLE 1, 3. For eGFR 15-29 mL/min, recommendations rely on FDA/EMA regulatory approval and pharmacokinetic modeling, as RCTs excluded these patients 1. For dialysis patients, evidence comes from observational registries and pharmacokinetic studies rather than RCTs 1, 4. Despite limited RCT evidence in severe renal impairment, registry data consistently favors apixaban over warfarin for both efficacy and safety 1, 5.