Published Online
on November 20, 2006

A more recent version of this article appeared on November 28, 2006

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Submitted on May 26, 2006
Revised on August 10, 2006
Accepted on September 8, 2006

A Once-Daily, Oral, Direct Factor Xa Inhibitor, Rivaroxaban (BAY 59-7939), for Thromboprophylaxis After Total Hip Replacement

Bengt I. Eriksson MD, PhD^*, Lars C. Borris MD, Ola E. Dahl MD, PhD, Sylvia Haas MD, Menno V. Huisman MD, PhD, Ajay K. Kakkar MD, PhD, Eva Muehlhofer MD, Christoph Dierig PhD, Frank Misselwitz MD, PhD, Peter Kälebo MD, PhD, for the ODIXa-HIP Study Investigators

From the Department of Orthopaedics, Sahlgrenska University Hospital/Östra, Gothenburg, Sweden (B.I.E.); Department of Orthopaedics, Aarhus University Hospital, Aarhus, Denmark (L.C.B.); Thrombosis Research Institute, London, UK (O.E.D., A.K.K.); Institute for Experimental Oncology and Therapy Research, Munich, Germany (S.H.); Department of General Internal Medicine and Endocrinology, Leiden University Medical Center, Leiden, the Netherlands (M.V.H.); Centre for Surgical Sciences, Barts and the London School of Medicine, London, UK (A.K.K.); Bayer HealthCare AG, Wuppertal, Germany (E.M., C.D., F.M.); and Department of Radiology, Östra Hospital, Gothenburg, Sweden (P.K.).

^* To whom correspondence should be addressed. E-mail: b.eriksson{at}orthop.gu.se.

Background--Rivaroxaban (BAY 59-7939)--an oral, direct Factor Xa inhibitor--could be an alternative to heparins and warfarin for the prevention and treatment of thromboembolic disorders.

Methods and Results--This randomized, double-blind, double-dummy, active-comparator-controlled, multinational, dose-ranging study assessed the efficacy and safety of once-daily rivaroxaban relative to enoxaparin for prevention of venous thromboembolism in patients undergoing elective total hip replacement. Patients (n=873) were randomized to once-daily oral rivaroxaban doses of 5, 10, 20, 30, or 40 mg (initiated 6 to 8 hours after surgery) or a once-daily subcutaneous enoxaparin dose of 40 mg (given the evening before and 6 hours after surgery). Study drugs were continued for an additional 5 to 9 days; mandatory bilateral venography was performed the following day. The primary end point (composite of any deep vein thrombosis, objectively confirmed pulmonary embolism, and all-cause mortality) was observed in 14.9%, 10.6%, 8.5%, 13.5%, 6.4%, and 25.2% of patients receiving 5, 10, 20, 30, and 40 mg rivaroxaban, and 40 mg enoxaparin, respectively (n=618, per-protocol population). No significant dose-response relationship was found for efficacy (P=0.0852). Major postoperative bleeding was observed in 2.3%, 0.7%, 4.3%, 4.9%, 5.1%, and 1.9% of patients receiving 5, 10, 20, 30, and 40 mg rivaroxaban, and 40 mg enoxaparin, respectively (n=845, safety population), representing a significant dose-response relationship (P=0.0391).

Conclusions--Rivaroxaban showed efficacy and safety similar to enoxaparin for thromboprophylaxis after total hip replacement, with the convenience of once-daily oral dosing and without the need for coagulation monitoring. When both efficacy and safety are considered, these results suggest that 10 mg rivaroxaban once daily should be investigated in phase III studies.

Key words: anticoagulants • coagulation • embolism • prevention • thrombosis

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