How long after stopping warfarin should the first dose of apixaban (direct oral anticoagulant) be given in a patient with atrial fibrillation and a bioprosthetic valve?

Timing of Apixaban After Warfarin Discontinuation in Atrial Fibrillation with Bioprosthetic Valve

The first dose of apixaban should be administered when the INR is below 2.0 after stopping warfarin in patients with atrial fibrillation and bioprosthetic valve.

Rationale and Evidence

The transition from warfarin to apixaban requires careful consideration to maintain effective anticoagulation while minimizing bleeding risk. This is particularly important in patients with atrial fibrillation and bioprosthetic valves who require continuous protection against thromboembolic events.

Transition Protocol

1. Stop warfarin and begin checking INR regularly
2. Start apixaban when INR falls below 2.0
3. Do not use bridging therapy with heparin during the transition unless the patient is at exceptionally high risk of thromboembolism

The 2019 AHA/ACC/HRS guidelines for atrial fibrillation management support the use of direct oral anticoagulants (DOACs) like apixaban in patients with AF and bioprosthetic valves 1. Small subgroups from the ARISTOTLE trial (41 patients with bioprosthetic valves) suggest that apixaban appears to be an equitable alternative to warfarin in patients with AF and remote bioprosthetic valve implantation 1.

Special Considerations for Bioprosthetic Valves

While patients with mechanical valves require warfarin, those with bioprosthetic valves can be safely managed with DOACs like apixaban after the initial post-implantation period. The ARISTOTLE trial data specifically demonstrated that apixaban was effective and safe in patients with AF and bioprosthetic valves 2.

Dosing Considerations

• Standard dosing: Apixaban 5 mg twice daily
• Reduced dosing: 2.5 mg twice daily if the patient meets at least two of the following criteria:
  • Age ≥80 years
  • Body weight ≤60 kg
  • Serum creatinine ≥1.5 mg/dL

Renal function should be assessed before initiating apixaban, as dosing is affected by creatinine clearance 1.

Monitoring During Transition

• Check INR daily or every other day after stopping warfarin until it falls below 2.0
• Once apixaban is started, no routine coagulation monitoring is required
• Regular follow-up is recommended to assess for bleeding complications or thromboembolic events

Potential Pitfalls and Caveats

• Avoid overlap: Do not administer apixaban and warfarin simultaneously as this increases bleeding risk
• Avoid delays: Prolonged periods without anticoagulation increase thromboembolic risk, especially in patients with AF and bioprosthetic valves
• Renal function: Ensure appropriate dosing based on renal function, as impaired renal function affects apixaban clearance
• Drug interactions: Be aware of medications that may interact with apixaban (e.g., strong inhibitors of CYP3A4 and P-glycoprotein)

Comparison with Other Scenarios

While the transition protocol from warfarin to apixaban is similar for most patients with AF, those with bioprosthetic valves represent a special population. The evidence supporting DOACs in this population is growing but still limited compared to the broader AF population. Nevertheless, the available data from ARISTOTLE suggests comparable efficacy and safety 2.

For patients with mechanical valves, DOACs including apixaban are contraindicated, and warfarin remains the standard of care 1.