article233

EINSTEIN CHOICE

"Rivaroxaban for the Prevention of Venous Thromboembolism". The New England Journal of Medicine. 2017.

Clinical Question

In patients with venous thromboembolism and in equipoise for continued anticoagulation, is rivaroxaban more effective than aspirin in preventing recurrent thrombosis without an increase in bleeding risk?

Bottom Line

Rivaroxaban, either at a treatment dose of 20 mg or thromboprophylactic dose of 10 mg, was more effective than aspirin at preventing recurrent venous thromboembolism without a significant increase in bleeding rates.

Major Points

Guidelines

The results of this study could inform future guidelines by providing an alternative to aspirin for extended VTE treatment, particularly in patients with equipoise regarding continued anticoagulation.

Design

- Multicenter, double-blind, randomized, placebo-controlled phase 3 trial
- N=3,396 patients with venous thromboembolism
- Interventions:
* Rivaroxaban 20 mg PO daily (n=1,107)
* Rivaroxaban 10 mg PO daily (n=1,127)
* Aspirin 100 mg PO daily (n=1,131)
- Mean follow-up: 351 days

Population

- Inclusion criteria: Patients 18 years or older with symptomatic proximal deep-vein thrombosis or pulmonary embolism who completed 6 to 12 months of anticoagulation therapy and were in equipoise regarding the need for continued anticoagulation.
- Exclusion criteria: Contraindication to continued anticoagulant therapy, need for extended therapeutic-dose anticoagulant agents, antiplatelet therapy, or creatinine clearance less than 30 ml per minute.
- Baseline characteristics: Similar across all three groups.

Interventions

- Patients were assigned to receive rivaroxaban (20 mg or 10 mg) or aspirin (100 mg) once daily with food for up to 12 months.

Outcomes

- Primary efficacy outcome: Symptomatic recurrent fatal or nonfatal VTE, and unexplained death where PE could not be ruled out.
* 20 mg rivaroxaban: 17 events (1.5%)
* 10 mg rivaroxaban: 13 events (1.2%)
* Aspirin: 50 events (4.4%)
- Principal safety outcome: Major bleeding
* 20 mg rivaroxaban: 6 events (0.5%)
* 10 mg rivaroxaban: 5 events (0.4%)
* Aspirin: 3 events (0.3%)

Criticisms

- The study excluded patients who required ongoing therapeutic doses of anticoagulants, thus its findings may not apply to this population.
- Study duration limited to up to 12 months; longer-term outcomes remain unknown.
- Noninferiority of 10 mg rivaroxaban to 20 mg rivaroxaban not established due to study power.

Funding

The study was funded by Bayer Pharmaceuticals.