Rivaroxaban for thromboprophylaxis after orthopaedic surgery: Pooled analysis of two studies

William D. Fisher; Bengt I. Eriksson; Kenneth A. Bauer; Lars Borris; Ola E. Dahl; Michael Gent; Sylvia Haas; Martin Homering; Menno V. Huisman; Ajay K. Kakkar; Peter Kälebo; Louis M. Kwong; Frank Misselwitz; Alexander G. G. Turpie

doi:10.1160/TH07-01-0055

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2007; 97(06): 931-937
DOI: 10.1160/TH07-01-0055

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Rivaroxaban for thromboprophylaxis after orthopaedic surgery: Pooled analysis of two studies

William D. Fisher

¹McGill University Health Centre, Montreal, Canada

,

Bengt I. Eriksson

²Sahlgrenska University Hospital/Östra, Gothenburg, Sweden

,

Kenneth A. Bauer

³Beth Israel Deaconess Medical Center, Boston, Massachussetts, USA

,

Lars Borris

⁴Aarhus University Hospital, Aarhus, Denmark

,

Ola E. Dahl

⁵Thrombosis Research Institute/International Surgical Thrombosis Forum, London, UK

,

Michael Gent

⁶Department of Medicine, HHS-General Hospital, Hamilton, Canada

,

Sylvia Haas

⁷Institute for Experimental Oncology and Therapy Research, Munich, Germany

,

Martin Homering

⁸Bayer HealthCare AG, Wuppertal, Germany

,

Menno V. Huisman

⁹Leiden University Medical Center, Leiden, The Netherlands

,

Ajay K. Kakkar

¹⁰Thrombosis Research Institute and Barts and the London School of Medicine, London, UK

,

Peter Kälebo

²Sahlgrenska University Hospital/Östra, Gothenburg, Sweden

,

Louis M. Kwong

¹¹Harbor-UCLA Medical Center, Torrance, California, USA

,

Frank Misselwitz

⁸Bayer HealthCare AG, Wuppertal, Germany

,

Alexander G. G. Turpie

⁶Department of Medicine, HHS-General Hospital, Hamilton, Canada

› Author Affiliations

Abstract

Summary

Rivaroxaban (BAY 59-7939) is an oral, direct factor Xa inhibitor in clinical development for the prevention and treatment of venous thromboembolism (VTE). This analysis of pooled results from two phase II studies of rivaroxaban for VTE prevention after major orthopaedic surgery aimed to strengthen the conclusions of the individual studies. One study was conducted in patients undergoing total hip replacement (THR; N=722), and one in patients undergoing total knee replacement (TKR; N=621). In both studies, patients were randomized, doubleblind, to oral, twice-daily (bid) rivaroxaban beginning after surgery, or subcutaneous enoxaparin (40 mg once daily beginning before THR, and 30 mg bid beginning after TKR). Treatment continued until mandatory bilateral venography was performed 5–9 days after surgery. Total VTE (deep vein thrombosis, pulmonary embolism, and all-cause mortality) occurred in 16.1–24.4% of per-protocol patients receiving rivaroxaban 5–60 mg, and 27.8% receiving enoxaparin (n=914). There was a flat dose response relationship between rivaroxaban and total VTE (p=0.39). Major bleeding (safety population, n=1,317) increased dose-dependently with rivaroxaban (p<0.001), occurring in 0.9%, 1.3%, 2.1%, 3.9%, and 7.0% of patients receiving rivaroxaban total daily doses of 5, 10, 20, 40, and 60 mg, respectively, versus 1.7% of patients receiving enoxaparin. No routine coagulation monitoring was performed, and there were no significant differences between dose response relationships with rivaroxaban after THR and TKR. Overall, rivaroxaban total daily doses of 5–20 mg had the most favorable balance of efficacy and safety, relative to enoxaparin, for the prevention of VTE after major orthopaedic surgery.

Keywords

Rivaroxaban - venous thromboembolism - orthopaedic surgery - total hip replacement - total knee replacement

Full Text

References

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