Switching from Warfarin to Apixaban for Atrial Fibrillation
Direct Transition Protocol
Stop warfarin and start apixaban when the INR drops below 2.0. 1 This FDA-approved approach avoids overlapping anticoagulation and eliminates the need for heparin bridging. 1
- No bridging anticoagulation is required during the transition period—simply discontinue warfarin and begin apixaban at the appropriate dose once INR <2.0. 1
- Monitor INR every 1–2 days after stopping warfarin until it falls below 2.0, then initiate apixaban immediately. 1
Determining the Correct Apixaban Dose
Use apixaban 5 mg twice daily for most patients. 2, 3 Reduce to 2.5 mg twice daily only when the patient meets at least two of the following three criteria: 2, 3, 1
- Calculate creatinine clearance using the Cockcroft-Gault equation (not eGFR), as this method was used in pivotal trials and aligns with FDA labeling. 2, 3
- For patients with moderate renal impairment (CrCl 30–59 mL/min), use the standard 5 mg twice daily dose unless they meet ≥2 of the dose-reduction criteria above. 2, 3
- For severe renal impairment (CrCl 15–29 mL/min), use 2.5 mg twice daily regardless of age or weight—severe renal dysfunction alone mandates dose reduction. 2, 3
Renal Function Considerations
| CrCl (mL/min) | Apixaban Dose | Rationale |
|---|---|---|
| >30 | 5 mg twice daily (unless ≥2 criteria met) | Standard dosing [2,3] |
| 15–29 | 2.5 mg twice daily (mandatory) | Severe renal impairment alone requires reduction [2,3] |
| <15 or dialysis | 5 mg twice daily; reduce to 2.5 mg if age ≥80 or weight ≤60 kg (only one criterion required) | FDA-approved for dialysis [2,3] |
- Apixaban has only 27% renal clearance, making it the safest direct oral anticoagulant in renal impairment compared to dabigatran (80%) or rivaroxaban (66%). 2, 3
- Reassess renal function at least annually, or every 3–6 months if CrCl <60 mL/min. 2, 3
Common Pitfalls to Avoid
- Do not reduce apixaban dose based on a single criterion—this is the most common prescribing error, with studies showing 9.4–40.4% of prescriptions involve inappropriate underdosing. 2
- Do not use eGFR for dosing decisions—always calculate CrCl with Cockcroft-Gault, as eGFR can produce significant dosing errors. 2, 3
- Do not add heparin bridging—the transition from warfarin to apixaban does not require parenteral anticoagulation. 1
- Do not start apixaban while INR is ≥2.0—wait until INR drops below 2.0 to avoid excessive anticoagulation. 1
Drug Interaction Adjustments
- Reduce apixaban to 2.5 mg twice daily when using combined P-glycoprotein and strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir, itraconazole) in patients otherwise receiving 5 mg twice daily. 2, 3
- Avoid apixaban entirely with strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin), as they markedly reduce apixaban levels. 2, 3
Practical Transition Steps
- Stop warfarin and check INR every 1–2 days. 1
- When INR <2.0, immediately start apixaban at the appropriate dose (5 mg or 2.5 mg twice daily based on the criteria above). 1
- Calculate CrCl using Cockcroft-Gault to confirm appropriate dosing. 2, 3
- Count dose-reduction criteria: 0–1 criterion → 5 mg twice daily; ≥2 criteria → 2.5 mg twice daily. 2, 3, 1
- Screen for drug interactions and adjust dose if needed. 2, 3
- No routine INR monitoring is required after starting apixaban. 2
Evidence Supporting This Approach
- The ARISTOTLE trial demonstrated that apixaban reduced hemorrhagic stroke by 49% versus warfarin (0.24%/year vs 0.47%/year; HR 0.44,95% CI 0.30–0.66), with a 31% reduction in major bleeding. 4
- Apixaban was superior to warfarin in patients with advanced CKD (CrCl 25–30 mL/min), with a 66% reduction in major bleeding (HR 0.34,95% CI 0.14–0.80). 5
- In dialysis patients, apixaban reduced major bleeding by 19% versus warfarin (HR 0.81,95% CI 0.70–0.94) without increasing recurrent VTE or mortality. 6