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

Thrombosis Journal

Philip S Wells⁸  Scott D Berkowitz³  Gary E Raskob⁷  Hervé Decousus^1,10  Bruce L Davidson¹  Alexander T Cohen⁴  Timothy A Brighton⁵  Henri Bounameaux²  Bonno van Bellen^1,12  Rupert Bauersachs⁹  Anthonie WA Lensing^1,11  Martin H Prins⁶ 

[1] University of Washington School of Medicine, Seattle, WA, USA;Department of Medicine, University Hospitals of Geneva, Faculty of Medicine, Geneva, Switzerland;Bayer HealthCare Pharmaceuticals, Whippany, NJ, USA;Department of Haematological Medicine, King’s College Hospital, London, UK;Department of Haematology, Prince of Wales Hospital, Sydney, New South Wales, Australia;Maastricht University Medical Center, Maastricht, The Netherlands;University of Oklahoma Health Sciences Center, College of Public Health, Oklahoma City, OK, USA;Department of Medicine, University of Ottawa and the Ottawa Hospital Research Institute, Ontario, Canada;Klinikum Darmstadt, Darmstadt, Germany;Service de Médecine et Thérapeutique, CHU Saint-Etienne, Saint-Etienne, France;Bayer HealthCare AG, Wuppertal, Germany;Hospital Beneficência Portuguesa, São Paulo, Brazil

关键词: Randomized controlled trials;    Venous thromboembolism;    Standard therapy;    Rivaroxaban;   

Others  :  838499
DOI  :  10.1186/1477-9560-11-21

 received in 2013-08-15, accepted in 2013-09-09,  发布年份 2013

【 摘 要 】

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; p_{noninferiority} < 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.

【 授权许可】

   
2013 Prins et al.; licensee BioMed Central Ltd.

【 图 表 】

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