Fixed-dose oral rivaroxaban appears noninferior to standard therapy for PE

Fixed-dose oral rivaroxaban is as effective as standard anticoagulant therapy for pulmonary embolism (PE) and may have a lower bleeding risk, a new study found.

Researchers conducted a four-year, randomized, open-label noninferiority trial with 4,832 patients who had acute symptomatic PE with or without deep vein thrombosis (DVT). Patients came from 263 sites in 38 countries.

Half received 15 mg of rivaroxaban twice a day for three weeks, followed by 20 mg once daily. The other, “standard therapy” patients received enoxaparin at a dose of 1.0 mg per kilogram of body weight twice daily, plus warfarin or acenocoumarol. Treatment lasted for three, six, or 12 months, with duration determined by the treating physician before randomization.

The primary efficacy outcome was symptomatic recurrent venous thromboembolism (VTE), and the primary safety outcome was a first major or clinically relevant nonmajor bleeding event. The study was supported by Bayer Healthcare and Janssen Pharmaceuticals.

There were 50 symptomatic recurrent VTE events in the rivaroxaban group (2.1%), which was noninferior to the 44 events in the standard therapy group (1.8%; hazard ratio [HR], 1.12; noninferiority margin, 2.0; P=0.003). The primary safety outcome occurred in 10.3% of rivaroxaban patients and 11.4% of standard-therapy patients (HR, 0.90; P=0.23). Major bleeding was seen in 26 patients (1.1%) in the rivaroxaban group and 52 patients (2.2%) in the standard-therapy group (HR, 0.49; P=0.003). Rates of other adverse outcomes were similar between the two groups. Results were published online March 26 by the New England Journal of Medicine.

Study strengths included that the population represented the real-life spectrum of patients who present with symptomatic PE, excluding those for whom fibrinolysis is planned, the authors said. Nearly 25% had extensive disease, and nearly 25% had concomitant symptomatic DVT, for example.

The study's open design may have caused a slight diagnostic-suspicion bias against rivaroxaban. There was a higher number of suspected VTE events in the rivaroxaban group than in the enoxaparin group, yet confirmed event rates were similar.

Overall, this study's findings, combined with the authors' previous study in DVT patients, “support the use of rivaroxaban as a single oral agent for patients with (VTE),” they said. The fixed-dose regimen will simplify treatment by obviating the need for laboratory monitoring that accompanies standard therapy, they said.