When is Xarelto (rivaroxaban) preferred over Eliquis (apixaban)?

When to Choose Rivaroxaban (Xarelto) Over Apixaban (Eliquis)

Based on current evidence, apixaban should generally be preferred over rivaroxaban for most patients with VTE due to lower bleeding risk, though rivaroxaban may be chosen for specific clinical scenarios including once-daily dosing preference, patients requiring extended prophylaxis after major cancer surgery, or when apixaban's twice-daily initiation dosing is impractical. 1, 2, 3

General Preference: Apixaban Over Rivaroxaban

The most recent high-quality evidence demonstrates that apixaban has superior safety compared to rivaroxaban:

• Real-world data from 2022 involving nearly 50,000 VTE patients showed apixaban was associated with significantly lower rates of both recurrent VTE (HR 0.77,95% CI 0.69-0.87) and major bleeding (HR 0.60,95% CI 0.53-0.69) compared to rivaroxaban. 3

• A 2024 meta-analysis of observational studies confirmed apixaban's significantly lower risk of major bleeding (RR 0.68,95% CI 0.61-0.76), clinically relevant non-major bleeding (RR 0.58), and any bleeding (RR 0.64) compared to rivaroxaban. 4

• The absolute reduction in bleeding probability with apixaban versus rivaroxaban was 1.1% within 2 months and 1.5% within 6 months. 3

Specific Scenarios Where Rivaroxaban May Be Preferred

1. Once-Daily Dosing Preference

Rivaroxaban offers once-daily dosing after the initial 3-week period (15 mg twice daily for 21 days, then 20 mg once daily), while apixaban requires twice-daily dosing throughout treatment. 5

• Consider rivaroxaban when medication adherence is a concern and once-daily dosing would significantly improve compliance. 1

2. Extended Thromboprophylaxis After Cancer Surgery

For patients requiring extended prophylaxis (up to 4 weeks) after major abdominal or pelvic cancer surgery:

• Rivaroxaban may be offered as an alternative to LMWH after an initial period of parenteral anticoagulation, though evidence remains limited (weak recommendation). 1
• Apixaban is also an option in this setting, but both DOACs have limited evidence compared to LMWH. 1

3. Patients With Gastrointestinal Malignancies

This is a critical caveat where neither rivaroxaban nor apixaban may be ideal:

• For patients with luminal GI malignancies (gastric, gastroesophageal), apixaban or LMWH are preferred over rivaroxaban or edoxaban due to lower GI bleeding risk. 1
• Rivaroxaban showed 25 more major GI bleeding events per 1,000 cases compared to LMWH in cancer-associated thrombosis. 1
• Apixaban showed only 2 more major GI bleeding events per 1,000 cases versus LMWH. 1

4. Reduced-Intensity Extended Therapy

Both drugs offer reduced-intensity dosing for extended VTE treatment beyond 6 months:

• Rivaroxaban 10 mg once daily (EINSTEIN-CHOICE trial) 1
• Apixaban 2.5 mg twice daily (AMPLIFY-EXTEND trial) 1

The once-daily rivaroxaban regimen may be preferred when simplicity is paramount for long-term adherence. 1

Clinical Decision Algorithm

Step 1: Assess bleeding risk

• High bleeding risk (especially GI) → Prefer apixaban 3, 4
• Standard bleeding risk → Prefer apixaban (lower bleeding overall) 3

Step 2: Evaluate adherence factors

• Poor adherence anticipated with twice-daily dosing → Consider rivaroxaban (once-daily after 3 weeks) 5
• Good adherence expected → Prefer apixaban 3

Step 3: Consider cancer-specific factors

• Luminal GI malignancy → Apixaban or LMWH preferred over rivaroxaban 1
• Non-GI cancer → Either DOAC acceptable, but apixaban has lower bleeding risk 1, 3
• Post-surgical extended prophylaxis → Rivaroxaban or apixaban may be offered after initial LMWH 1

Step 4: Extended therapy considerations

• If planning reduced-intensity extended therapy and once-daily dosing is critical → Rivaroxaban 10 mg daily 1
• If twice-daily dosing acceptable → Apixaban 2.5 mg twice daily 1

Important Caveats

• All DOACs (apixaban, rivaroxaban, dabigatran, edoxaban) are recommended over warfarin for non-cancer VTE treatment. 1

• For cancer-associated thrombosis, oral factor Xa inhibitors (apixaban, rivaroxaban, edoxaban) are recommended over LMWH, except in luminal GI malignancies where apixaban or LMWH are preferred. 1

• Rivaroxaban requires administration with food for proper absorption, while apixaban can be taken without regard to meals. This may influence choice in patients with eating difficulties. 5

• Both drugs should be avoided in severe renal impairment (CrCl <30 mL/min for rivaroxaban; insufficient data for apixaban in dialysis patients). 1