Oral Rivaroxaban for the Treatment of Symptomatic Pulmonary Embolism

Study Questions:

What is the safety and efficacy of oral rivaroxaban for the treatment of symptomatic pulmonary embolism?


EINSTEIN-PE was a randomized, open-label, event-driven, noninferiority trial involving 4,832 patients who had acute symptomatic pulmonary embolism with or without deep-vein thrombosis. The investigators compared rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily) with standard therapy with enoxaparin followed by an adjusted-dose vitamin K antagonist for 3, 6, or 12 months. The primary efficacy outcome was symptomatic recurrent venous thromboembolism. The principal safety outcome was major or clinically relevant nonmajor bleeding. The primary efficacy analysis was performed on an intention-to-treat basis with the use of a Cox proportional-hazards model stratified according to the intended duration of treatment, with adjustment for the presence or absence of cancer at baseline. Kaplan–Meier curves were generated to display the distribution of events over time.


Rivaroxaban was noninferior to standard therapy (noninferiority margin, 2.0; p = 0.003) for the primary efficacy outcome, with 50 events in the rivaroxaban group (2.1%) versus 44 events in the standard-therapy group (1.8%) (hazard ratio [HR], 1.12; 95% confidence interval [CI], 0.75-1.68). The principal safety outcome occurred in 10.3% of patients in the rivaroxaban group and 11.4% of those in the standard therapy group (HR, 0.90; 95% CI, 0.76-1.07; p = 0.23). Major bleeding was observed in 26 patients (1.1%) in the rivaroxaban group and 52 patients (2.2%) in the standard-therapy group (HR, 0.49; 95% CI, 0.31-0.79; p = 0.003). Rates of other adverse events were similar in the two groups.


The authors concluded that a fixed-dose regimen of rivaroxaban alone was noninferior to standard therapy for the initial and long-term treatment of pulmonary embolism.


This study suggests that in patients with symptomatic pulmonary embolism, oral rivaroxaban alone provided protection from recurrent venous thromboembolism that was similar to the protection provided by standard therapy, with similar bleeding rates. Overall, these findings, along with those of previous evaluation involving patients with deep-vein thrombosis, support the use of rivaroxaban as a single oral agent for patients with venous thromboembolism.

Clinical Topics: Anticoagulation Management, Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine, Anticoagulation Management and Venothromboembolism

Keywords: Vitamin K, Neoplasms, Morpholines, Pyridinolcarbamate, Pulmonary Embolism, Thiophenes, Venous Thromboembolism, Intention, Proportional Hazards Models, Enoxaparin, Research Personnel, Venous Thrombosis, Confidence Intervals

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