What is the comparison between Rivaroxaban (Xarelto) and Apixaban (Eliquis) for treating atrial fibrillation or venous thromboembolism?

Rivaroxaban vs Apixaban for Atrial Fibrillation and Venous Thromboembolism

Apixaban is superior to rivaroxaban for treating atrial fibrillation, with significantly lower rates of major ischemic and hemorrhagic events and better overall safety profile. 1

Efficacy Comparison

Atrial Fibrillation

• Apixaban demonstrates superior efficacy compared to rivaroxaban in preventing stroke and systemic embolism in patients with atrial fibrillation, with an adjusted rate of 13.4 vs 16.1 per 1000 person-years (hazard ratio 1.18 for rivaroxaban vs apixaban) 1
• Apixaban is associated with significantly fewer major ischemic events (7.6 vs 8.6 per 1000 person-years) compared to rivaroxaban in patients with atrial fibrillation 1
• Both medications are recommended for stroke prevention in nonvalvular AF, but apixaban has demonstrated superiority to warfarin while rivaroxaban has only shown non-inferiority 2

Venous Thromboembolism

• For VTE treatment, both medications are effective with different dosing regimens:
  • Apixaban: 10 mg twice daily for 7 days followed by 5 mg twice daily 2
  • Rivaroxaban: 15 mg twice daily with food for 21 days followed by 20 mg daily with food 2
• For extended VTE treatment (after 6 months), both offer reduced-dose options:
  • Apixaban: 2.5 mg twice daily 2
  • Rivaroxaban: 10 mg daily 2

Safety Profile

Bleeding Risk

• Apixaban has a significantly lower risk of major hemorrhagic events compared to rivaroxaban (5.9 vs 7.5 per 1000 person-years) 1
• Rivaroxaban is associated with more than double the risk of nonfatal extracranial bleeding compared to apixaban (39.7 vs 18.5 per 1000 person-years) 1
• Fatal bleeding events are also higher with rivaroxaban compared to apixaban (1.4 vs 1.0 per 1000 person-years) 1
• Both medications have lower rates of intracranial hemorrhage compared to warfarin, but apixaban has the most favorable profile 2

Mortality

• Total mortality is higher with rivaroxaban compared to apixaban (44.2 vs 41.0 per 1000 person-years) 1
• Fatal ischemic/hemorrhagic events are more common with rivaroxaban than apixaban (4.5 vs 3.3 per 1000 person-years) 1

Pharmacokinetic Differences

• Apixaban is administered twice daily, which provides more stable blood levels with lower peak-to-trough ratios 3
• Rivaroxaban is typically administered once daily (for AF) and should be taken with food to ensure adequate absorption 2
• Apixaban is predominantly eliminated hepatically and is highly protein bound 2
• Rivaroxaban is predominantly excreted by the kidneys 2
• Apixaban reaches steady-state concentrations by day 3, with an accumulation index of 1.3-1.9 3

Dosing Considerations

Renal Function

• For patients with renal impairment:
  • Apixaban: Standard dose can be used down to CrCl 15 mL/min; dose reduction to 2.5 mg twice daily if two of three criteria are met: age ≥80 years, weight ≤60 kg, or serum creatinine ≥1.5 mg/dL 2
  • Rivaroxaban: Dose reduction to 15 mg daily if CrCl 15-50 mL/min; not recommended if CrCl <15 mL/min 2

Special Populations

• For elderly patients (≥80 years), apixaban may be preferred due to its better safety profile and specific dose adjustment criteria 2, 1
• For patients with low body weight (≤60 kg), apixaban has specific dose adjustment criteria that may provide better safety 2

Clinical Decision-Making Algorithm

1. For atrial fibrillation patients:

   • Choose apixaban as first-line therapy due to superior efficacy and safety profile 1
   • Consider rivaroxaban only if compliance with twice-daily dosing is a concern 2

2. For VTE treatment:

   • Either agent is appropriate for initial treatment 2
   • For extended therapy, consider patient-specific factors:
     • Apixaban if bleeding risk is high 2
     • Rivaroxaban if once-daily dosing would improve adherence 2

3. For patients with renal impairment:

   • For severe renal impairment (CrCl 15-30 mL/min), apixaban is preferred 2
   • Neither drug is recommended for CrCl <15 mL/min 2

Common Pitfalls and Caveats

• Inappropriate dose reduction of either medication without meeting specific criteria can lead to underdosing and increased thromboembolic risk 2
• Failure to consider drug-drug interactions, particularly with CYP3A4 inhibitors/inducers, can affect drug levels 2
• Transitioning between anticoagulants requires careful timing and monitoring to prevent gaps in anticoagulation 4, 5
• Neither drug has routine laboratory monitoring requirements, but specific assays are available if needed in emergency situations 5
• Reversal strategies differ: specific reversal agents are now available but may have different availability and efficacy between the two drugs 5