Are Eliquis (apixaban) and Xarelto (rivaroxaban) interchangeable for atrial fibrillation (AFib)?

Apixaban and Rivaroxaban Are Not Interchangeable for Atrial Fibrillation

Apixaban (Eliquis) and rivaroxaban (Xarelto) are not interchangeable for atrial fibrillation despite both being direct oral anticoagulants (DOACs). While both medications are effective for stroke prevention in non-valvular atrial fibrillation, they have important differences in dosing regimens, efficacy profiles, and bleeding risk that make direct substitution inappropriate.

Key Differences Between Apixaban and Rivaroxaban

Dosing Regimens

• Apixaban: Twice daily dosing (5 mg BID or 2.5 mg BID for dose reduction) 1
• Rivaroxaban: Once daily dosing (20 mg daily or 15 mg daily for dose reduction) 1

Efficacy Profile

• Apixaban: Demonstrated superior efficacy compared to warfarin in the ARISTOTLE trial with 21% reduction in stroke or systemic embolism 1
• Rivaroxaban: Showed non-inferiority to warfarin in the ROCKET-AF trial 1

Bleeding Risk

• Apixaban: Associated with lower risks of bleeding, including intracranial hemorrhage 1
• Rivaroxaban: Bleeding risk comparable to warfarin 1

Dose Adjustment Criteria

Both medications require dose adjustments based on different criteria:

Apixaban Dose Reduction (to 2.5 mg BID)

Required if patient has at least 2 of the following:

• Age ≥80 years
• Body weight ≤60 kg
• Serum creatinine ≥1.5 mg/dL 1

Rivaroxaban Dose Reduction (to 15 mg daily)

Required for:

• Moderate renal impairment (CrCl 30-49 mL/min)
• High bleeding risk (HAS-BLED score ≥3) 1

Clinical Implications of Non-Interchangeability

Pharmacokinetic Differences

• Different half-lives and peak-trough profiles affect the consequences of missed doses
• Rivaroxaban must be taken with food for optimal absorption, while apixaban can be taken without regard to meals

Renal Function Considerations

• Both medications have different recommendations for patients with renal impairment
• Neither should be used in severe renal impairment (CrCl <15 mL/min) 1
• Apixaban may be preferred in patients with moderate renal impairment due to its lower renal clearance 1

Perioperative Management

• Different interruption protocols before invasive procedures:
  • For low bleeding risk procedures: both should be stopped at least 24 hours before
  • For high bleeding risk procedures: both should be stopped at least 48 hours before 1

Switching Between Agents

When switching between these medications:

1. Stop the current DOAC
2. Check renal function to determine appropriate dosing of the new agent
3. Start the new DOAC when the next dose of the previous agent would have been due
4. For patients with high thrombotic risk, consider minimizing the time without anticoagulation

Pitfalls to Avoid

• Automatic substitution: Never substitute one DOAC for another without reassessing patient-specific factors
• Improper dosing: Inappropriate dose reduction occurs frequently in clinical practice (60.8% of reduced-dose apixaban prescriptions don't meet criteria) 2
• Inadequate monitoring: Regular assessment of renal function is required for both medications 1
• Drug interactions: Different interaction profiles may affect safety and efficacy

Conclusion

While both apixaban and rivaroxaban are effective DOACs for stroke prevention in atrial fibrillation, their differences in dosing, efficacy, and safety profiles mean they cannot be considered interchangeable. Selection between these agents should be based on patient-specific factors including renal function, bleeding risk, medication adherence capability, and comorbidities.