In a patient with acute pulmonary embolism requiring oral anticoagulation, is Xarelto (rivaroxaban) or Eliquis (apixaban) the preferred agent?

Apixaban (Eliquis) is preferred over rivaroxaban (Xarelto) for pulmonary embolism anticoagulation

Based on the most recent head-to-head comparative evidence, apixaban demonstrates superior effectiveness and safety compared to rivaroxaban, with significantly lower rates of both recurrent VTE and major bleeding.

Evidence Supporting Apixaban Preference

The 2019 retrospective cohort analysis of 15,254 patients directly comparing apixaban versus rivaroxaban found 1:

• Recurrent VTE reduction: Apixaban reduced recurrent pulmonary embolism risk by 63% (HR 0.37,95% CI 0.24-0.55, p<0.0001) 1
• Major bleeding reduction: Apixaban reduced major bleeding events by 46% (HR 0.54,95% CI 0.37-0.82, p=0.0031) 1
• Absolute risk differences: Recurrent VTE occurred at 3 per 100 person-years with apixaban versus 7 per 100 person-years with rivaroxaban; major bleeding occurred at 3 per 100 person-years with apixaban versus 6 per 100 person-years with rivaroxaban 1

Guideline Context

While the 2021 CHEST guidelines recommend apixaban, dabigatran, edoxaban, or rivaroxaban equally over vitamin K antagonists (strong recommendation, moderate-certainty evidence), they explicitly note that "the choice of anticoagulant for the treatment phase of VTE necessitates consideration of patient-specific factors" 2. The guidelines acknowledge these agents as a class but do not address head-to-head comparisons between individual DOACs 2.

The 2020 European Society of Cardiology guidelines similarly recommend NOACs as a class without distinguishing between individual agents 2.

Clinical Implications for Morbidity and Mortality

The superior outcomes with apixaban directly impact the key clinical endpoints that matter most:

• Lower recurrent PE risk translates to reduced mortality risk, as recurrent VTE carries significant morbidity and potential for fatal outcomes 1
• Lower major bleeding risk reduces hemorrhagic complications that can be life-threatening and significantly impair quality of life 1
• Both benefits occur simultaneously with apixaban, creating a more favorable risk-benefit profile 1

Special Populations

Cancer-Associated Thrombosis

In patients with cancer and PE, the 2021 CHEST guidelines note that apixaban does NOT increase GI bleeding risk compared to LMWH (2 more events per 1,000 cases), while rivaroxaban/edoxaban DO increase GI bleeding (25 more events per 1,000 cases) 2. Apixaban is explicitly preferred for patients with luminal GI malignancies 2.

Dosing Considerations

• Apixaban: 10 mg twice daily for 7 days, then 5 mg twice daily 3
• Rivaroxaban: 15 mg twice daily for 21 days, then 20 mg once daily 3

The longer high-dose period with rivaroxaban (21 days versus 7 days) may contribute to increased bleeding risk 3.

Common Pitfalls to Avoid

• Do not assume all DOACs are equivalent: The class effect assumption from guidelines does not account for head-to-head comparative data showing meaningful differences in outcomes 1
• Do not overlook bleeding risk in cancer patients: Rivaroxaban carries significantly higher GI bleeding risk in patients with luminal GI malignancies 2
• Do not ignore renal function: Both agents require dose adjustment or avoidance in severe renal impairment (CrCl <30 mL/min), but this applies equally to both 3

Treatment Duration

Regardless of which DOAC is chosen, all PE patients require:

• Minimum 3 months of therapeutic anticoagulation 2, 4
• Discontinuation after 3 months if provoked by major transient/reversible risk factor 2, 4
• Indefinite anticoagulation for recurrent VTE, unprovoked PE, or active cancer 2, 4

For extended therapy beyond 6 months, reduced-dose apixaban (2.5 mg twice daily) should be considered 2.