In a 78-year-old woman with atrial fibrillation, poor balance and high fall risk, should she be switched from rivaroxaban (Xarelto) to apixaban (Eliquis)?

Switch to Apixaban for This High-Fall-Risk Patient

In a 78-year-old woman with atrial fibrillation, poor balance, and high fall risk currently on rivaroxaban, you should switch to apixaban 5 mg twice daily (or 2.5 mg twice daily if she meets ≥2 dose-reduction criteria). Apixaban has superior bleeding safety—particularly for intracranial hemorrhage—which is the critical concern in fall-prone patients, while maintaining equivalent stroke prevention.

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Why Apixaban Is Preferred in High-Fall-Risk Patients

Intracranial Hemorrhage Risk

• Apixaban reduced intracranial hemorrhage by 49% compared to warfarin (0.24%/year vs 0.47%/year) in the ARISTOTLE trial, and this advantage extends to comparisons with rivaroxaban 1, 2.
• In a large Medicare study of 581,451 patients, rivaroxaban was associated with 26% higher risk of major hemorrhagic events compared to apixaban (HR 1.26,95% CI 1.16-1.36), including significantly more fatal extracranial bleeding 3.
• A Canadian population study of 73,342 older AF patients found apixaban reduced major bleeding by 35-37% compared to rivaroxaban in both high-risk (HR 0.69) and low-risk (HR 0.63) bleeding populations, with no difference in stroke prevention 4, 5.

Pharmacokinetic Safety Margin

• Apixaban has only 27% renal clearance compared to rivaroxaban's 35-66% renal elimination, providing a wider safety margin as patients age and renal function fluctuates 1, 6.
• This lower renal dependence is particularly important in elderly patients with declining kidney function, which is common in the 78-year-old age group 2, 6.

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Determining the Correct Apixaban Dose

The "2-of-3" Dose-Reduction Algorithm

Use apixaban 2.5 mg twice daily ONLY if your patient meets ≥2 of these three criteria 1, 2:

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

If she meets 0-1 criteria, use the standard 5 mg twice daily dose 1, 2.

Critical Dosing Pitfall to Avoid

• Do NOT reduce the dose based solely on fall risk, perceived frailty, or age 78 years alone—these are not validated dose-reduction criteria 1, 2.
• Studies show that 9.4-40.4% of apixaban prescriptions involve inappropriate underdosing, often driven by clinician concern about bleeding risk when formal criteria are not met 2.
• Underdosing increases stroke risk without improving bleeding safety 2, 7.

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Practical Switching Protocol

Step-by-Step Transition

1. Stop rivaroxaban after the last dose 2.
2. Start apixaban at the next scheduled dosing time (no washout period needed; rivaroxaban's half-life is 5-9 hours) 2.
3. Calculate creatinine clearance using Cockcroft-Gault equation (not eGFR) to verify renal function 2.
4. Apply the 2-of-3 criteria to determine 5 mg vs 2.5 mg twice-daily dosing 2.

Renal Function Monitoring

• Reassess renal function at least annually, or every 3-6 months if CrCl <60 mL/min 2.
• Use the Cockcroft-Gault equation consistently, as this was the method used in pivotal trials and FDA labeling 2.

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Why Not Continue Rivaroxaban?

Comparative Safety Evidence

• The 2021 JAMA study of Medicare beneficiaries showed rivaroxaban had 18% higher risk of the composite primary outcome (major ischemic or hemorrhagic events) compared to apixaban (HR 1.18,95% CI 1.12-1.24) 3.
• Rivaroxaban doubled the risk of nonfatal extracranial bleeding (HR 2.07) and increased fatal bleeding by 41% (HR 1.41) compared to apixaban 3.
• These risks were present in both standard-dose and reduced-dose rivaroxaban groups 3.

Real-World Dosing Concerns

• A German study found that 52.1% of patients receiving reduced-dose rivaroxaban (15 mg) did not meet labeling criteria for dose reduction, suggesting widespread inappropriate underdosing 7.
• Inappropriate rivaroxaban dose reduction was associated with higher ischemic stroke rates in real-world data 8.

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Special Considerations for Fall-Risk Patients

The Fall-Risk Paradox

• Anticoagulation remains beneficial even in high-fall-risk patients because the stroke risk from untreated AF far exceeds the intracranial hemorrhage risk from falls 1.
• However, choosing the anticoagulant with the lowest intracranial bleeding risk is critical—this is apixaban 1, 2, 3.

Guideline Support

• The 2012 ESC guidelines note that apixaban had lower major bleeding than warfarin (31% reduction) and suggest it may be preferable in patients where bleeding risk is a concern 1.
• The 2014 AHA/ACC/HRS guidelines emphasize that apixaban demonstrated superiority over warfarin for both efficacy and safety, including in older patients 1.

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Drug Interactions to Screen

Reduce Apixaban to 2.5 mg Twice Daily If:

• Patient is taking combined P-glycoprotein AND strong CYP3A4 inhibitors (ketoconazole, ritonavir, itraconazole) 2.

Avoid Apixaban If:

• Patient is taking strong CYP3A4 inducers (rifampin, carbamazepine, phenytoin) 2.

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Monitoring After the Switch

No Routine Lab Monitoring Required

• No INR monitoring needed with apixaban 1.
• Monitor clinically for bleeding symptoms, particularly gastrointestinal bleeding in elderly patients 2.

When to Reassess

• Renal function annually (or every 3-6 months if declining) 2.
• Review fall-prevention strategies and consider physical therapy to address balance issues 2.

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Bottom Line Algorithm

1. Assess the 3 dose-reduction criteria (age, weight, serum creatinine).
2. Count criteria: 0-1 → 5 mg twice daily; ≥2 → 2.5 mg twice daily.
3. Calculate CrCl using Cockcroft-Gault.
4. Screen for drug interactions (P-gp/CYP3A4 inhibitors/inducers).
5. Stop rivaroxaban and start apixaban at the next scheduled dose.
6. Monitor renal function per schedule above.

The evidence strongly favors apixaban in this high-fall-risk, elderly patient due to its superior bleeding safety profile, particularly for intracranial hemorrhage, while maintaining equivalent stroke prevention 3, 4, 5.