What is the best course of action for a patient experiencing recurrent Deep Vein Thrombosis (DVT) while on Eliquis (apixaban)?

Management of Recurrent DVTs on Apixaban (Eliquis)

For patients experiencing recurrent Deep Vein Thrombosis (DVT) while on apixaban, switching to therapeutic dose low-molecular-weight heparin (LMWH) is recommended as the most effective strategy to reduce morbidity and mortality. 1

Assessment of Recurrent DVT on Apixaban

When a patient experiences recurrent DVT while on apixaban therapy, consider:

• Confirm medication adherence to apixaban at the correct dose (5 mg twice daily for standard treatment) 2
• Verify that the initial lead-in dosing was appropriate (10 mg twice daily for the first 7 days) 2
• Rule out any drug interactions that may reduce apixaban efficacy 1
• Assess for underlying conditions that may increase thrombotic risk, particularly active cancer 1

Treatment Algorithm for Recurrent DVT on Apixaban

First-line Approach:

• Switch to therapeutic LMWH (e.g., enoxaparin 1 mg/kg twice daily or 1.5 mg/kg once daily) 1
  • LMWHs have demonstrated superior efficacy in managing recurrent thrombosis, particularly in patients with cancer-associated thrombosis 1
  • This approach has the strongest evidence for reducing recurrent VTE events 1

Alternative Options:

• Consider dose adjustment of apixaban to 10 mg twice daily (if patient was on 5 mg twice daily maintenance dose) 2, 3

  • Limited evidence supports this approach, and it may increase bleeding risk 4

• Switch to a different direct oral anticoagulant (DOAC) such as rivaroxaban or edoxaban 1

  • Rivaroxaban: 15 mg twice daily for 21 days, then 20 mg once daily 1
  • Edoxaban: Requires 5 days of parenteral anticoagulation before initiating 60 mg daily 1

• Consider warfarin therapy (target INR 2.0-3.0) if DOACs and LMWH are not feasible 1

  • Requires more frequent monitoring but may be effective in certain patients 1

Special Considerations

Cancer-Associated Thrombosis:

• For patients with active cancer and recurrent DVT on apixaban, LMWH is strongly preferred 1, 5
• LMWH regimens with the strongest evidence include:
  • Dalteparin: 200 IU/kg once daily for the first month, followed by 150 IU/kg once daily 5
  • Enoxaparin: 1 mg/kg twice daily or 1.5 mg/kg once daily 1

Renal Impairment:

• For patients with CrCl <30 mL/min, avoid apixaban and consider dose-adjusted LMWH or warfarin 1
• For moderate renal impairment (CrCl 30-50 mL/min), use caution with all DOACs 1

Potential Pitfalls and Caveats:

• Failure to assess medication adherence is a common oversight in evaluating recurrent thrombosis 3
• Drug-drug interactions (particularly P-glycoprotein and CYP3A4 inhibitors/inducers) may affect apixaban efficacy 4
• Patients with gastrointestinal or genitourinary malignancies may have higher bleeding risk with DOACs and might benefit from LMWH 1
• Inferior vena cava filters should only be considered when anticoagulation is absolutely contraindicated 1

Duration of Treatment After Recurrent DVT

• Extended anticoagulation (indefinite duration) is recommended for patients with recurrent unprovoked DVT 1
• Regular reassessment of bleeding risk is necessary for patients on indefinite anticoagulation 1

Monitoring Recommendations

• Clinical follow-up within 2-4 weeks after changing anticoagulation strategy 3
• Consider imaging to confirm resolution of thrombus if symptoms persist 3
• Regular assessment of bleeding risk factors throughout treatment 1