What are alternative treatments to Eliquis (apixaban) for a patient with atrial fibrillation (AFib)?

Alternatives to Eliquis (Apixaban) for Atrial Fibrillation

For patients with atrial fibrillation requiring anticoagulation, the primary alternatives to apixaban are rivaroxaban, dabigatran, and edoxaban—all direct oral anticoagulants (DOACs) that have demonstrated efficacy in stroke prevention—or warfarin for patients who cannot tolerate DOACs. 1, 2, 3

Direct Oral Anticoagulant (DOAC) Alternatives

Rivaroxaban

• Dosing: 20 mg once daily (15 mg once daily if CrCl 15-50 mL/min) 1
• Evidence: Non-inferior to warfarin for stroke prevention in AF, with similar efficacy to apixaban for ischemic stroke or systemic embolism 4, 5
• Key consideration: Once-daily dosing may improve adherence in some patients, though missing a single dose creates a longer gap in anticoagulation coverage 6
• Comparative safety: Associated with higher gastrointestinal bleeding rates compared to apixaban (HR 1.39,95% CI 1.27-1.52) 4

Dabigatran

• Dosing: 150 mg twice daily (or 110 mg twice daily, though 110 mg dose not available in US) 1
• Dose reduction: 75 mg twice daily if CrCl 15-30 mL/min (US dosing) 1
• Evidence: Superior to warfarin for stroke prevention at 150 mg dose, with similar efficacy to apixaban 3, 5
• Comparative safety: Higher gastrointestinal bleeding risk than apixaban (HR 1.23,95% CI 1.07-1.42) 4
• Unique advantage: Idarucizumab available as specific reversal agent 3

Edoxaban

• Dosing: 60 mg once daily 1
• Dose reduction: 30 mg once daily if weight ≤60 kg, CrCl 15-50 mL/min, or concomitant strong P-glycoprotein inhibitor 1
• Evidence: Non-inferior to warfarin for stroke prevention 3
• Comparative safety: Higher gastrointestinal bleeding risk than apixaban (HR 1.30,95% CI 1.10-1.54) 4
• Key consideration: Once-daily dosing option 1

Warfarin as an Alternative

When to Consider Warfarin

• Mechanical heart valves: DOACs are contraindicated; warfarin is the only option 1
• Severe renal impairment: For patients with CrCl <15 mL/min not on dialysis, warfarin may be preferred as DOACs are contraindicated or have limited data 1, 2
• Cost considerations: Warfarin has significantly lower acquisition costs, though requires INR monitoring 5
• Patient already stable on warfarin: If well-controlled (time in therapeutic range >65-70%), compliant, and without complications, continuing warfarin is reasonable 1

Warfarin Dosing and Monitoring

• Target INR: 2.0-3.0 for nonvalvular AF 1, 2
• Monitoring: Regular INR checks required, with dose adjustments to maintain therapeutic range 1
• Limitations: Narrow therapeutic window, multiple drug and food interactions, and higher intracranial hemorrhage risk compared to DOACs 3, 5

Comparative Effectiveness Summary

Stroke Prevention

• All four DOACs demonstrate similar efficacy for preventing ischemic stroke or systemic embolism when compared head-to-head in real-world data 4
• No substantial differences observed between apixaban, dabigatran, edoxaban, and rivaroxaban for stroke prevention (all HRs crossing 1.0) 4

Bleeding Risk Profile

• Apixaban has the lowest gastrointestinal bleeding risk among all DOACs in large multinational cohort studies 4
• All DOACs demonstrate lower intracranial hemorrhage rates compared to warfarin 3, 5
• Apixaban showed 31% reduction in major bleeding versus warfarin in ARISTOTLE trial 7

Special Population Considerations

Elderly Patients (≥80 years)

• All DOACs maintain consistent safety and efficacy profiles in patients aged 80 years or older 4
• Dose reduction criteria apply for specific DOACs based on age combined with other factors 1

Chronic Kidney Disease

• CrCl 30-50 mL/min: All DOACs can be used with standard or reduced dosing per specific criteria 1
• CrCl 15-30 mL/min: Apixaban 5 mg twice daily (or 2.5 mg if ≥2 reduction criteria), dabigatran 75 mg twice daily (US), rivaroxaban 15 mg daily, edoxaban 30 mg daily 1
• CrCl <15 mL/min not on dialysis: DOACs contraindicated; warfarin preferred 1, 2
• Apixaban maintains lower GIB risk versus rivaroxaban even in CKD patients (HR 0.68,95% CI 0.59-0.77) 4

Patients Requiring Antiplatelet Therapy

• If recent PCI, use DOAC plus clopidogrel (not aspirin) after brief periprocedural triple therapy 1
• Rivaroxaban 15 mg once daily specifically studied in combination with antiplatelet therapy in PIONEER AF-PCI 1

Practical Decision-Making Algorithm

Step 1: Determine if patient has mechanical heart valve or severe renal impairment (CrCl <15 mL/min not on dialysis)

• If yes → Warfarin 1

Step 2: If patient already stable on warfarin with good INR control and no complications

• Consider continuing warfarin 1

Step 3: For DOAC selection, prioritize based on:

• Gastrointestinal bleeding risk: If high concern → Apixaban (lowest GIB risk) 4
• Need for reversal agent: If high bleeding risk → Dabigatran (idarucizumab available) or Apixaban (andexanet alfa available) 3
• Adherence concerns: Consider once-daily options (rivaroxaban or edoxaban), though evidence for improved adherence is mixed 6
• Renal function: Match DOAC to appropriate dosing based on CrCl 1

Common Pitfalls to Avoid

• Do not underdose DOACs without meeting specific dose-reduction criteria, as this increases stroke risk without reducing bleeding 1
• Do not use aspirin monotherapy for stroke prevention in AF—it provides minimal protection (21% risk reduction) compared to anticoagulation 8
• Do not combine DOACs with dual antiplatelet therapy long-term, as bleeding risk substantially increases 1
• Do not assume all DOACs are interchangeable—gastrointestinal bleeding rates differ significantly, with apixaban demonstrating lowest risk 4