How do you transition from Warfarin (Coumadin) to Eliquis (Apixaban) for a patient with atrial fibrillation?

Transitioning from Warfarin to Eliquis (Apixaban) for Atrial Fibrillation

Discontinue warfarin and start apixaban when the INR falls below 2.0. 1

The Transition Protocol

The FDA-approved method for switching from warfarin to apixaban is straightforward and does not require bridging anticoagulation:

• Stop warfarin immediately when you decide to transition 1
• Monitor the INR until it drops below 2.0 1
• Start apixaban at the appropriate dose once INR <2.0, at the time the next warfarin dose would have been given 1
• No bridging anticoagulation is needed during this transition period 2, 1

This approach is explicitly outlined in the apixaban prescribing information and represents the safest, evidence-based method. 1

Critical Timing Considerations

Do not start apixaban while the INR remains ≥2.0, as this creates overlapping anticoagulation and significantly increases bleeding risk without reducing thrombotic events. 2

The transition period typically takes 2-5 days depending on the patient's baseline INR and warfarin metabolism:

• Check INR 2-3 days after stopping warfarin in most patients 1
• For patients with INR >3.0 at baseline, recheck daily until INR falls below 2.0 1
• For patients with INR 2.0-3.0 at baseline, checking INR every 2-3 days is reasonable 1

Apixaban Dosing After Transition

Once the INR is below 2.0, select the appropriate apixaban dose based on patient characteristics:

Standard dose: 5 mg twice daily for most patients 1

Reduced dose: 2.5 mg twice daily if the patient has at least 2 of the following 3 criteria: 1

• Age ≥80 years
• Body weight ≤60 kg
• Serum creatinine ≥1.5 mg/dL

Why Bridging Is Not Needed (and Potentially Harmful)

Bridging anticoagulation during the warfarin-to-apixaban transition increases bleeding risk 2-3 fold without reducing stroke risk. 2

The evidence against bridging is compelling:

• No reduction in ischemic events occurs with bridging therapy in nonvalvular atrial fibrillation patients 2
• Major hemorrhage rates increase significantly with bridging (2.7% vs 0.5%, p=0.01) 2
• The RE-LY trial demonstrated bridging resulted in higher major hemorrhage (6.5% vs 1.8%, p<0.001) with no difference in thrombosis rates 2

The only patients who might require bridging are those with mechanical heart valves (particularly older-generation or mitral position valves), but these patients should not be on apixaban at all—warfarin is mandatory for mechanical valves. 3, 4

Special Populations Requiring Dose Adjustment

Renal function assessment is mandatory before starting apixaban and should be reassessed at least annually. 5, 4

For patients with advanced chronic kidney disease:

• CrCl 25-30 mL/min: Standard dosing (5 mg twice daily or 2.5 mg twice daily based on dose-reduction criteria) is appropriate and safe 6
• CrCl 15-25 mL/min: Consider dose reduction, though evidence is limited 4
• CrCl <15 mL/min or dialysis: Apixaban may be reasonable, but warfarin is preferred by most guidelines 5, 4

For patients on strong dual P-gp and CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir): 1

• Reduce the 5 mg twice daily dose to 2.5 mg twice daily
• Avoid apixaban entirely if patient already requires 2.5 mg twice daily dosing

Common Pitfalls to Avoid

Do not start apixaban before the INR drops below 2.0, as warfarin continues to exert anticoagulant effects even after discontinuation, and overlapping therapy dramatically increases bleeding risk. 2, 1

Do not use apixaban in patients with mechanical heart valves or moderate-to-severe mitral stenosis—these patients must remain on warfarin. 3, 5, 4

Do not combine apixaban with antiplatelet therapy (aspirin or clopidogrel) unless the patient has an acute vascular event or recent PCI, as this increases bleeding risk by more than 50%. 2

Do not assume all patients need the same dose—carefully assess for dose-reduction criteria (age ≥80, weight ≤60 kg, creatinine ≥1.5 mg/dL) before prescribing. 1

Patient Education During Transition

Patients must understand several key points during the transition:

• Continue warfarin until instructed to stop and do not start apixaban until the INR check confirms it is safe 1
• Apixaban requires twice-daily dosing (unlike warfarin's once-daily dosing), and missed doses significantly reduce protection 1
• No dietary restrictions are needed with apixaban, unlike warfarin's vitamin K interactions 5
• No routine INR monitoring is required once on apixaban, but renal function must be checked at least annually 5, 4
• Report any bleeding immediately, as apixaban has no readily available reversal agent in most settings (though andexanet alfa exists) 1

Monitoring After Transition

Once apixaban is started:

• No routine coagulation monitoring (INR, PT, aPTT) is needed or useful 5
• Assess renal function at least annually, more frequently if CrCl 30-60 mL/min or if patient develops acute illness 5, 4
• Reassess bleeding risk factors and manage modifiable risks (hypertension, concomitant NSAIDs, alcohol use) 3
• Confirm medication adherence at each visit, as DOACs have short half-lives and missed doses leave patients unprotected 5

When Cardioversion Is Planned

If cardioversion is anticipated during or shortly after the transition:

• Ensure at least 3 weeks of therapeutic anticoagulation (either warfarin with INR 2.0-3.0 or apixaban at appropriate dose) before cardioversion if AF duration ≥48 hours or unknown 3
• TEE-guided cardioversion can be performed with abbreviated anticoagulation if no thrombus is visualized, but therapeutic anticoagulation must still be established before the procedure 3
• Continue anticoagulation for at least 4 weeks post-cardioversion regardless of whether sinus rhythm is maintained, as atrial mechanical dysfunction persists 3