Oral Rivaroxaban for the Treatment of Symptomatic Pulmonary Embolism Journal Articles uri icon

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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 standard-therapy 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.).


  • Schulman, Sam
  • EINSTEIN–PE Investigators
  • Büller, Harry R
  • Prins, Martin H
  • Lensin, Anthonie WA
  • Decousus, Hervé
  • Jacobson, Barry F
  • Minar, Erich
  • Chlumsky, Jaromir
  • Verhamme, Peter
  • Wells, Phil
  • Agnelli, Giancarlo
  • Cohen, Alexander
  • Berkowitz, Scott D
  • Bounameaux, Henri
  • Davidson, Bruce L
  • Misselwitz, Frank
  • Gallus, Alex S
  • Raskob, Gary E
  • Schellong, Sebastian
  • Segers, Annelise

publication date

  • April 5, 2012

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