What is the best approach for transitioning a patient with a history of atrial fibrillation, deep vein thrombosis, or pulmonary embolism from warfarin (coumarin) to Eliquis (apixaban)?

Transitioning from Warfarin to Eliquis (Apixaban)

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

Transition Protocol

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

• Stop warfarin immediately and monitor the INR 1
• Begin apixaban when INR drops below 2.0 1
• Do not use bridging anticoagulation during the transition period 1
• Start apixaban at the appropriate maintenance dose based on patient characteristics (see dosing below) 1

Apixaban Dosing After Transition

For Atrial Fibrillation

• Standard dose: 5 mg orally twice daily for most patients 1
• Reduced dose: 2.5 mg orally twice daily if the patient has at least TWO of the following: 1
  • Age ≥80 years
  • Body weight ≤60 kg
  • Serum creatinine ≥1.5 mg/dL

For Venous Thromboembolism (DVT/PE)

• If transitioning during acute treatment phase: 5 mg orally twice daily (assuming the patient has already completed the initial 7 days at 10 mg twice daily) 1
• If transitioning during extended/secondary prevention phase: 2.5 mg orally twice daily after at least 6 months of initial treatment 1

Why This Approach is Superior

Direct oral anticoagulants like apixaban are recommended over warfarin for eligible patients with atrial fibrillation because they demonstrate superior or noninferior efficacy with significantly lower bleeding risk. 2 The 2020 ACC/AHA guidelines give a Class 1, Level A recommendation for DOACs over warfarin in DOAC-eligible patients. 2

Key advantages of apixaban specifically include:

• Fewer overall strokes and systemic emboli compared to warfarin 3
• Significantly fewer major bleeding events, particularly intracranial hemorrhages 3
• Lower all-cause mortality compared to warfarin 3
• No routine INR monitoring required 4, 5
• Predictable pharmacokinetics with multiple elimination pathways 5

Critical Timing Considerations

The transition must occur when INR is below 2.0 because:

• Warfarin affects INR measurements, making initial INR readings unreliable for guiding warfarin dosing during overlap 1
• Starting apixaban at INR <2.0 prevents excessive anticoagulation while maintaining adequate thromboembolic protection 1
• The rapid onset of apixaban (peak effect in 3-4 hours) provides immediate anticoagulation once warfarin effect wanes 5

Common Pitfalls to Avoid

• Do NOT bridge with heparin or LMWH during the transition - this increases bleeding risk without added benefit for routine transitions 1
• Do NOT start apixaban while INR remains ≥2.0 - this creates excessive anticoagulation and bleeding risk 1
• Do NOT use the acute VTE dosing (10 mg twice daily) when transitioning from warfarin unless the patient is within the first 7 days of acute VTE treatment 1
• Do NOT underdose patients with atrial fibrillation - the 2.5 mg twice daily dose for AF requires TWO dose-reduction criteria, not just one 1
• Do NOT assume all patients need dose reduction for renal impairment - apixaban has multiple elimination pathways and is safer in renal dysfunction than other DOACs 3, 6

Special Populations Requiring Attention

Patients with Severe Renal Impairment

• Patients with CrCl 15-29 mL/min can still use apixaban with appropriate dose reduction 3
• Dialysis patients may benefit from apixaban over warfarin with lower bleeding risk, though data are limited 3
• Standard-dose apixaban (5 mg twice daily) showed better outcomes than low-dose in dialysis patients 3

Patients with Cancer-Associated VTE

• Apixaban is an acceptable alternative to LMWH for cancer-associated thrombosis, though LMWH remains preferred in some guidelines 2
• Use the full VTE treatment dose (5 mg twice daily after initial 7 days), not the reduced dose 2, 1

High Thrombotic Risk Patients

• Ensure adequate overlap timing - do not allow INR to drop too low before starting apixaban in patients with recent thrombotic events 1
• Consider starting apixaban when INR reaches 2.0-2.5 rather than waiting for <2.0 in very high-risk patients (e.g., within 1 month of acute VTE) 1

Monitoring After Transition

• No routine anticoagulation monitoring required 4, 5
• Assess renal function, body weight, and bleeding risk regularly 3
• Evaluate for drug interactions, particularly with combined P-gp and strong CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir) which require dose reduction 1
• Ensure medication adherence - missed doses significantly increase thrombotic risk 1