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
1   McGill University Health Centre, Montreal, Canada
,
Bengt I. Eriksson
2   Sahlgrenska University Hospital/Östra, Gothenburg, Sweden
,
Kenneth A. Bauer
3   Beth Israel Deaconess Medical Center, Boston, Massachussetts, USA
,
Lars Borris
4   Aarhus University Hospital, Aarhus, Denmark
,
Ola E. Dahl
5   Thrombosis Research Institute/International Surgical Thrombosis Forum, London, UK
,
Michael Gent
6   Department of Medicine, HHS-General Hospital, Hamilton, Canada
,
Sylvia Haas
7   Institute for Experimental Oncology and Therapy Research, Munich, Germany
,
Martin Homering
8   Bayer HealthCare AG, Wuppertal, Germany
,
Menno V. Huisman
9   Leiden University Medical Center, Leiden, The Netherlands
,
Ajay K. Kakkar
10   Thrombosis Research Institute and Barts and the London School of Medicine, London, UK
,
Peter Kälebo
2   Sahlgrenska University Hospital/Östra, Gothenburg, Sweden
,
Louis M. Kwong
11   Harbor-UCLA Medical Center, Torrance, California, USA
,
Frank Misselwitz
8   Bayer HealthCare AG, Wuppertal, Germany
,
Alexander G. G. Turpie
6   Department of Medicine, HHS-General Hospital, Hamilton, Canada
› Author Affiliations

Financial support: The original studies and the analysis reported in this manuscript were sponsored by Bayer HealthCare AG. F. Misselwitz and M. Homering are employees of Bayer Health-Care AG. W.D. Fisher, L. Kwong, and B.I. Eriksson were investigators in the studies and received grants for enrolling patients. P. Kälebo received honoraria for adjudication of the venograms during the studies. All steering committee members (A.G.G. Turpie, B.I. Eriksson, K.A. Bauer, L. Borris, O.E. Dahl, M. Gent, S. Haas, M.V. Huisman, A.K. Kakkar, L.M. Kwong, and W.D. Fisher) received honoraria for their participation. The steering committees had the final responsibility for the study protocol, the analyses, and the manuscript.
Further Information

Publication History

Received 25 January 2007

Accepted after revision 26 March 2007

Publication Date:
27 November 2017 (online)

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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.

Footnote: This paper was presented at the American Society of Hematology meeting, Atlanta, Georgia, December 12, 2005.