Oral rivaroxaban for the treatment of symptomatic pulmonary embolism

H Buller, M Prins, A Lensing, H Decousus, Barry Jacobson, E Minar, J Chlumsky, Peter Verhamme, P Wells, G Agnelli, A Cohen, Scott Berkowitz, Henri Bounameaux, B Davidson, F Misselwitz, Alexander Gallus, G Raskob, Sebastian Schellong, Annelise Segers

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    BACKGROUND: A fixed-dose regimen of rivaroxaban, an oral factor Xa inhibitor, has been shown to be as effective as standard anticoagulant therapy for the treatment of deep-vein thrombosis, without the need for laboratory monitoring. This approach may also simplify the treatment of pulmonary embolism. METHODS: In a randomized, open-label, event-driven, noninferiority trial involving 4832 patients who had acute symptomatic pulmonary embolism with or without deep-vein thrombosis, we 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. RESULTS: 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, 1.12; 95% confidence interval [CI], 0.75 to 1.68). The principal safety outcome occurred in 10.3% of patients in the rivaroxaban group and 11.4% of those in the standardtherapy group (hazard ratio, 0.90; 95% CI, 0.76 to 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 (hazard ratio, 0.49; 95% CI, 0.31 to 0.79; P = 0.003). Rates of other adverse events were similar in the two groups. CONCLUSIONS: A fixed-dose regimen of rivaroxaban alone was noninferior to standard therapy for the initial and long-term treatment of pulmonary embolism and had a potentially improved benefit-risk profile. (Funded by Bayer HealthCare and Janssen Pharmaceuticals; EINSTEIN-PE ClinicalTrials.gov number, NCT00439777.).

    Original languageEnglish
    Pages (from-to)1287-1297
    Number of pages11
    JournalNew England Journal of Medicine
    Issue number14
    Publication statusPublished - 2012

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    Buller, H., Prins, M., Lensing, A., Decousus, H., Jacobson, B., Minar, E., Chlumsky, J., Verhamme, P., Wells, P., Agnelli, G., Cohen, A., Berkowitz, S., Bounameaux, H., Davidson, B., Misselwitz, F., Gallus, A., Raskob, G., Schellong, S., & Segers, A. (2012). Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. New England Journal of Medicine, 366(14), 1287-1297. https://doi.org/10.1056/NEJMoa1113572