What are the recommendations for changing Direct Oral Anticoagulants (DOACs) if a patient develops Deep Vein Thrombosis (DVT) while on Eliquis (Apixaban)?

Management of Breakthrough DVT on Apixaban (Eliquis)

When a patient develops DVT while on therapeutic apixaban, switch to low molecular weight heparin (LMWH) rather than another DOAC, and conduct a thorough investigation to identify the underlying cause of anticoagulation failure. 1

Initial Assessment and Investigation

Before making any therapeutic changes, you must determine whether this represents true anticoagulation failure or inadequate therapy:

• Verify medication adherence - Confirm the patient has been taking apixaban as prescribed, including correct dosing frequency (twice daily) and timing 1
• Review current dosing - Ensure the patient is on treatment-dose apixaban (10 mg twice daily for first 7 days, then 5 mg twice daily), not the reduced 2.5 mg twice daily dose used only for extended secondary prevention after completing at least 6 months of full-dose therapy 2
• Check for drug interactions - Identify any P-glycoprotein inducers (rifampin, carbamazepine, phenytoin, St. John's wort) that could reduce apixaban levels 2
• Assess for underlying prothrombotic conditions - Screen for active malignancy, antiphospholipid syndrome, occult cancer, or other hypercoagulable states that may overwhelm standard anticoagulation 1
• Evaluate renal function - While apixaban has minimal renal clearance (27%), severe renal impairment (CrCl <15 mL/min) may affect drug levels 2

Recommended Anticoagulation Change

Switch to LMWH as the preferred alternative anticoagulant for breakthrough thrombosis on apixaban 1. The American Society of Hematology 2020 guidelines specifically suggest LMWH over switching to another DOAC for patients with breakthrough VTE during therapeutic anticoagulation, though this recommendation is based on very low certainty evidence 1.

Rationale for LMWH:

• Predictable pharmacokinetics - LMWH provides consistent anticoagulation with weight-based dosing and does not rely on the same pathways as apixaban 1
• Monitoring capability - Anti-Xa levels can be measured if needed to confirm therapeutic anticoagulation 1
• Established efficacy - LMWH has decades of evidence in treating VTE, including in challenging populations 1

When NOT to Switch from Apixaban:

This recommendation does not apply if the breakthrough DVT occurred due to:

• Poor INR control - This guidance is specifically for patients on therapeutic VKA with poor control; for apixaban, this translates to documented non-adherence or subtherapeutic dosing 1
• Prophylactic dosing error - If the patient was mistakenly on 2.5 mg twice daily instead of treatment dose, simply correcting to 5 mg twice daily (after 10 mg twice daily for 7 days) may be appropriate 2

Alternative DOAC Considerations

While the ASH guidelines suggest LMWH over another DOAC, no evidence demonstrates superiority of one DOAC over another for VTE treatment 1. If LMWH is not feasible (patient preference, access issues, inability to self-inject), switching to a different DOAC class may be considered:

• Switch to rivaroxaban or edoxaban (factor Xa inhibitors with different pharmacokinetic profiles) 1
• Switch to dabigatran (direct thrombin inhibitor with entirely different mechanism) 1
• Ensure 5 days of parenteral anticoagulation (LMWH or UFH) before starting dabigatran or edoxaban 1

However, this approach lacks evidence and should only be pursued after excluding correctable causes of anticoagulation failure 1.

Specific Clinical Scenarios

Active Malignancy:

• LMWH remains preferred for cancer-associated thrombosis, particularly with breakthrough events 1
• If oral therapy strongly preferred, rivaroxaban or edoxaban may be considered, but avoid in gastrointestinal malignancies due to increased bleeding risk 3

Antiphospholipid Syndrome:

• DOACs should be avoided entirely - switch to therapeutic LMWH or warfarin (target INR 2.0-3.0) 1
• DOACs have shown increased thrombotic risk in triple-positive antiphospholipid syndrome 1

Severe Renal Impairment (CrCl <30 mL/min):

• LMWH with dose adjustment or unfractionated heparin are preferred 1
• All DOACs have contraindications or require significant dose reductions at this level of renal function 2

Duration of Anticoagulation After Switch

• Minimum 3 months of therapeutic anticoagulation from the time of the breakthrough event 1
• Consider indefinite anticoagulation if no reversible cause is identified, as breakthrough thrombosis on therapeutic anticoagulation represents very high recurrence risk 1
• Reassess annually if continuing extended anticoagulation 1

Common Pitfalls to Avoid

• Do not simply increase apixaban dose - there is no evidence supporting higher than standard treatment doses, and no approved higher dosing regimen exists 2
• Do not switch DOACs without investigation - identifying the cause of failure is essential to prevent recurrence 1
• Do not use reduced-dose DOACs (apixaban 2.5 mg or rivaroxaban 10 mg) for acute breakthrough thrombosis - these doses are only for extended secondary prevention after completing full treatment 1, 2
• Do not assume all breakthrough events represent drug failure - non-adherence is the most common cause and should be thoroughly assessed 1