What are the alternatives to Eliquis (apixaban) for anticoagulation?

Alternatives to Eliquis (Apixaban) for Anticoagulation

The primary alternatives to apixaban are the other direct oral anticoagulants (DOACs)—rivaroxaban, dabigatran, and edoxaban—which are all acceptable substitutes depending on the indication, with rivaroxaban and dabigatran having the most extensive evidence base across multiple indications. 1

DOAC Alternatives by Indication

For Atrial Fibrillation (Stroke Prevention)

The following DOACs are guideline-recommended alternatives with specific dosing 1:

• Rivaroxaban: 20 mg once daily (reduce to 15 mg once daily if CrCl ≤50 mL/min) 1
• Dabigatran: 150 mg twice daily or 110 mg twice daily (no pre-specified dose reduction criteria in the pivotal trial, though 110 mg twice daily if age ≥80 years, concomitant verapamil, or increased GI bleeding risk per product labeling) 1
• Edoxaban: 60 mg once daily (reduce to 30 mg once daily if weight ≤60 kg, CrCl ≤50 mL/min, or concomitant strong P-gp inhibitor) 1

Recent comparative effectiveness data from over 500,000 patients with atrial fibrillation showed that apixaban had lower gastrointestinal bleeding risk compared to all other DOACs, but similar rates of stroke, intracranial hemorrhage, and mortality. 2 This suggests that if GI bleeding risk is a concern, apixaban may be preferable, but if switching away from apixaban, the other DOACs provide comparable stroke prevention.

For Venous Thromboembolism (DVT/PE) Treatment

Initial treatment phase 1:

• Rivaroxaban: 15 mg twice daily for 21 days, then 20 mg once daily 1, 3, 4
• Dabigatran: Requires initial parenteral anticoagulation (heparin/LMWH) before starting dabigatran 150 mg twice daily 1
• Edoxaban: Requires initial parenteral anticoagulation (heparin/LMWH) before starting edoxaban 60 mg once daily (same dose reductions as for atrial fibrillation) 1

Extended treatment phase for unprovoked VTE 1:

• Reduced-dose rivaroxaban: 10 mg once daily (studied in EINSTEIN-CHOICE) 1, 3
• Full-dose rivaroxaban: 20 mg once daily 1
• Dabigatran: 150 mg twice daily (continued from initial treatment) 1
• Edoxaban: 60 mg once daily (with appropriate dose reductions) 1

The CHEST guidelines suggest using reduced-dose DOACs (rivaroxaban 10 mg daily or apixaban 2.5 mg twice daily) over full-dose for extended-phase anticoagulation, balancing efficacy against bleeding risk. 1

For VTE Prophylaxis After Major Orthopedic Surgery

Alternative DOACs include 1:

• Rivaroxaban: 10 mg once daily 1
• Dabigatran: 220 mg once daily 1
• Edoxaban: 30 mg once daily 1

Warfarin as an Alternative

Warfarin (a vitamin K antagonist) remains an acceptable alternative when DOACs cannot be used, though guidelines give preference to DOACs over warfarin for most indications due to better safety profiles and no need for routine monitoring. 1 Warfarin requires:

• INR monitoring with target range typically 2.0-3.0
• Bridging with parenteral anticoagulation for acute VTE
• Dietary considerations and multiple drug interactions

Special Situations

Cancer-Associated VTE

Low molecular weight heparin (LMWH) or a DOAC (including apixaban alternatives like rivaroxaban or edoxaban) are preferred over warfarin. 1 If apixaban is unavailable, rivaroxaban or edoxaban are reasonable alternatives with similar efficacy. 5

Heparin-Induced Thrombocytopenia (HIT)

If anticoagulation is needed in HIT, alternatives include 1:

• Fondaparinux: Subcutaneous once daily, no cross-reactivity with anti-PF4 antibodies 1
• Argatroban: Direct thrombin inhibitor, requires IV administration and monitoring 1
• Danaparoid: If available regionally 1
• Rivaroxaban: May be considered after acute phase, though less evidence than fondaparinux 1

Renal Impairment

All DOACs require dose adjustment or avoidance in severe renal impairment (CrCl <15-30 mL/min depending on the agent). 5 Apixaban has 27% renal clearance, making it favorable in renal dysfunction, but if switching is necessary:

• Rivaroxaban and edoxaban have specific dose reductions for CrCl ≤50 mL/min 1
• Warfarin may be preferred in severe renal impairment (CrCl <15 mL/min) as it has no renal elimination 1

Key Clinical Considerations

When selecting an alternative to apixaban, consider 1, 2:

• Dosing frequency: Rivaroxaban and edoxaban are once daily; dabigatran is twice daily
• Need for initial parenteral therapy: Rivaroxaban does not require bridging for VTE; dabigatran and edoxaban do 1
• Renal function: Apixaban and rivaroxaban may be better tolerated in moderate renal impairment 5
• GI bleeding risk: Apixaban has the lowest GI bleeding risk among DOACs; if this was the reason for switching away from apixaban, consider warfarin or reduced-dose DOAC 2
• Drug interactions: All DOACs interact with strong P-gp and CYP3A4 inhibitors/inducers 1

Common pitfall: Do not assume all DOACs are interchangeable without considering the specific indication and dosing regimen—rivaroxaban and apixaban have unique dosing for acute VTE treatment that differs from their maintenance dosing. 1, 3