Oral rivaroxaban for the treatment of symptomatic pulmonary embolism

N Engl J Med. 2012 Apr 5;366(14):1287-97. doi: 10.1056/NEJMoa1113572. Epub 2012 Mar 26.

Abstract

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.).

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use*
  • Drug Therapy, Combination
  • Enoxaparin / adverse effects
  • Enoxaparin / therapeutic use
  • Female
  • Follow-Up Studies
  • Hemorrhage / chemically induced
  • Humans
  • International Normalized Ratio
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Morpholines / adverse effects
  • Morpholines / therapeutic use*
  • Pulmonary Embolism / drug therapy*
  • Pulmonary Embolism / mortality
  • Recurrence
  • Rivaroxaban
  • Thiophenes / adverse effects
  • Thiophenes / therapeutic use*
  • Treatment Outcome
  • Vitamin K / antagonists & inhibitors

Substances

  • Anticoagulants
  • Enoxaparin
  • Morpholines
  • Thiophenes
  • Vitamin K
  • Rivaroxaban

Associated data

  • ClinicalTrials.gov/NCT00439777