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Open Access Highly Accessed Original clinical investigation

Oral rivaroxaban versus standard therapy for the treatment of symptomatic venous thromboembolism: a pooled analysis of the EINSTEIN-DVT and PE randomized studies

Martin H Prins1*, Anthonie WA Lensing2, Rupert Bauersachs3, Bonno van Bellen4, Henri Bounameaux5, Timothy A Brighton6, Alexander T Cohen7, Bruce L Davidson8, Hervé Decousus9, Gary E Raskob10, Scott D Berkowitz11, Philip S Wells12 and on behalf of the EINSTEIN Investigators

Author Affiliations

1 Maastricht University Medical Center, Maastricht, The Netherlands

2 Bayer HealthCare AG, Wuppertal, Germany

3 Klinikum Darmstadt, Darmstadt, Germany

4 Hospital Beneficência Portuguesa, São Paulo, Brazil

5 Department of Medicine, University Hospitals of Geneva, Faculty of Medicine, Geneva, Switzerland

6 Department of Haematology, Prince of Wales Hospital, Sydney, New South Wales, Australia

7 Department of Haematological Medicine, King’s College Hospital, London, UK

8 University of Washington School of Medicine, Seattle, WA, USA

9 Service de Médecine et Thérapeutique, CHU Saint-Etienne, Saint-Etienne, France

10 University of Oklahoma Health Sciences Center, College of Public Health, Oklahoma City, OK, USA

11 Bayer HealthCare Pharmaceuticals, Whippany, NJ, USA

12 Department of Medicine, University of Ottawa and the Ottawa Hospital Research Institute, Ontario, Canada

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Thrombosis Journal 2013, 11:21  doi:10.1186/1477-9560-11-21

Published: 20 September 2013

Abstract

Background

Standard treatment for venous thromboembolism (VTE) consists of a heparin combined with vitamin K antagonists. Direct oral anticoagulants have been investigated for acute and extended treatment of symptomatic VTE; their use could avoid parenteral treatment and/or laboratory monitoring of anticoagulant effects.

Methods

A prespecified pooled analysis of the EINSTEIN-DVT and EINSTEIN-PE studies compared the efficacy and safety of rivaroxaban (15 mg twice-daily for 21 days, followed by 20 mg once-daily) with standard-therapy (enoxaparin 1.0 mg/kg twice-daily and warfarin or acenocoumarol). Patients were treated for 3, 6, or 12 months and followed for suspected recurrent VTE and bleeding. The prespecified noninferiority margin was 1.75.

Results

A total of 8282 patients were enrolled; 4151 received rivaroxaban and 4131 received standard-therapy. The primary efficacy outcome occurred in 86 (2.1%) rivaroxaban-treated patients compared with 95 (2.3%) standard-therapy-treated patients (hazard ratio, 0.89; 95% confidence interval [CI], 0.66–1.19; pnoninferiority < 0.001). Major bleeding was observed in 40 (1.0%) and 72 (1.7%) patients in the rivaroxaban and standard-therapy groups, respectively (hazard ratio, 0.54; 95% CI, 0.37–0.79; p = 0.002). In key subgroups, including fragile patients, cancer patients, patients presenting with large clots, and those with a history of recurrent VTE, the efficacy and safety of rivaroxaban were similar compared with standard-therapy.

Conclusion

The single-drug approach with rivaroxaban resulted in similar efficacy to standard-therapy and was associated with a significantly lower rate of major bleeding. Efficacy and safety results were consistent among key patient subgroups.

Trial registration

EINSTEIN-PE: ClinicalTrials.gov, NCT00439777; EINSTEIN-DVT: ClinicalTrials.gov, NCT00440193.

Keywords:
Rivaroxaban; Standard therapy; Venous thromboembolism; Randomized controlled trials