Alternatives to Eliquis (Apixaban) for Atrial Fibrillation
Direct oral anticoagulants (DOACs) including rivaroxaban, dabigatran, and edoxaban are the recommended alternatives to apixaban for patients with atrial fibrillation, with all DOACs being preferred over warfarin in eligible patients. 1
DOAC Alternatives to Apixaban
Rivaroxaban
- Dosing: 20 mg once daily with the evening meal for patients with normal to mild renal impairment (CrCl ≥50 mL/min)
- Reduced dose: 15 mg once daily for patients with moderate renal impairment (CrCl 15-49 mL/min) 1
- Advantages: Once-daily dosing may improve adherence
- Considerations: Must be taken with food to ensure adequate absorption
Dabigatran
- Dosing: 150 mg twice daily for most patients
- Reduced dose: 110 mg twice daily for patients ≥80 years, concomitant verapamil, or increased risk of GI bleeding 1
- Unique feature: Only DOAC with a specific reversal agent (idarucizumab)
- Considerations: Higher rate of dyspepsia compared to other DOACs
Edoxaban
- Dosing: 60 mg once daily
- Reduced dose: 30 mg once daily if weight ≤60 kg, CrCl ≤50 mL/min, or concomitant therapy with strong P-glycoprotein inhibitor 1
- Advantages: Once-daily dosing
Vitamin K Antagonist Alternative
Warfarin
- Traditional anticoagulant requiring regular INR monitoring
- Target INR: 2.0-3.0 for atrial fibrillation 2
- Indications where warfarin is preferred over DOACs:
- Mechanical heart valves
- Moderate-to-severe mitral stenosis
- Severe renal impairment (CrCl <15 mL/min) in most cases
- Pregnancy (DOACs contraindicated)
Comparative Effectiveness
When comparing the alternatives to apixaban:
- Apixaban appears to have a better safety profile with less major bleeding compared to dabigatran 150 mg and rivaroxaban 3
- A 2022 study showed that apixaban was associated with lower rates of ischemic stroke or systemic embolism (HR 0.57) and bleeding (HR 0.51) compared to rivaroxaban in patients with AF and valvular heart disease 4
- All DOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) are recommended over warfarin in eligible patients due to:
- At least non-inferior efficacy in preventing stroke
- Lower risk of intracranial hemorrhage
- No need for routine INR monitoring 1
Selection Algorithm Based on Patient Characteristics
For patients with normal renal function:
- Any DOAC is appropriate (apixaban, rivaroxaban, dabigatran, edoxaban)
- Consider once-daily options (rivaroxaban, edoxaban) for patients with adherence concerns
For patients with renal impairment:
- CrCl 15-29 mL/min: Apixaban 2.5 mg twice daily or rivaroxaban 15 mg once daily
- CrCl <15 mL/min or dialysis: Limited data; apixaban 2.5 mg twice daily may be considered 5
For patients with high bleeding risk:
- Apixaban or edoxaban may be preferred due to lower bleeding rates
- Avoid dabigatran in patients with high GI bleeding risk
For patients with valvular AF:
- Mechanical heart valves or moderate-to-severe mitral stenosis: Warfarin only
- Other valvular disease: DOACs are acceptable 1
Important Caveats and Considerations
- Medication adherence: Once-daily medications (rivaroxaban, edoxaban) may improve compliance compared to twice-daily options (apixaban, dabigatran)
- Cost and insurance coverage: May influence choice between alternatives
- Drug interactions: All DOACs interact with P-glycoprotein inhibitors; rivaroxaban and apixaban also interact with strong CYP3A4 inhibitors
- Reversal agents: Consider availability of specific reversal agents (idarucizumab for dabigatran, andexanet alfa for factor Xa inhibitors)
- Monitoring: While routine coagulation monitoring is not required for DOACs, regular assessment of renal function is essential 5
Remember that all DOACs are contraindicated in pregnancy, breastfeeding, mechanical heart valves, and moderate-to-severe mitral stenosis. For these patients, warfarin remains the standard of care despite the need for regular INR monitoring.