This study was presented as an oral communication at the American Society of Hematology Meeting, Atlanta, GA, USA, in December 2007, and the abstract published in Blood 2007;110:98a.
Prevention of venous thromboembolism with an oral factor Xa inhibitor, YM150, after total hip arthroplasty. A dose finding study (ONYX-2)
Version of Record online: 17 JAN 2010
© 2010 International Society on Thrombosis and Haemostasis
Journal of Thrombosis and Haemostasis
Volume 8, Issue 4, pages 714–721, April 2010
How to Cite
ERIKSSON, B. I., TURPIE, A. G. G., LASSEN, M. R., PRINS, M. H., AGNELLI, G., KÄLEBO, P., WETHERILL, G., WILPSHAAR, J. W., MEEMS, L. and FOR THE ONYX-2 STUDY GROUP (2010), Prevention of venous thromboembolism with an oral factor Xa inhibitor, YM150, after total hip arthroplasty. A dose finding study (ONYX-2). Journal of Thrombosis and Haemostasis, 8: 714–721. doi: 10.1111/j.1538-7836.2010.03748.x
- Issue online: 23 MAR 2010
- Version of Record online: 17 JAN 2010
- Received 2 July 2009, accepted 5 January 2010
- direct factor Xa inhibitor;
- oral anticoagulant;
- total hip arthroplasty;
- venous thromboembolism;
Background: Anticoagulant prophylaxis substantially reduces the risk of venous thromboembolism (VTE) after major orthopedic surgery. The direct factor Xa inhibitor YM150 is currently under investigation for the prevention of VTE, stroke and ischemic vascular events in patients after orthopedic surgery, with atrial fibrillation and with acute coronary syndrome, respectively.
Objectives: To investigate the efficacy and safety of YM150 for the prevention of VTE following elective total hip arthroplasty.
Patients/methods: Patients were randomized to postoperative, once-daily, oral YM150 (5, 10, 30, 60 or 120 mg) (double-blind) or preoperative subcutaneous (open label) enoxaparin (40 mg) for 5 weeks. The primary efficacy endpoint comprised VTE diagnosed by mandatory bilateral venography or verified symptomatic deep vein thrombosis (DVT) plus all deaths up to 9 days after surgery. The primary safety outcome was major bleeding up to 9 days after surgery.
Results: Primary efficacy endpoint: of 1017 patients randomized, 960 patients were evaluable for safety and 729 patients for efficacy. A dose-related decrease in VTE incidence from YM150 5 to 60 mg (P = 0.0005) and from 5 to120 mg (P = 0.0002) was found. The VTE incidence was 27.4%, 31.7%, 19.3%, 13.3% and 14.5% for 5, 10, 30, 60 and 120 mg YM150, respectively, and 18.9% for enoxaparin. Primary safety endpoint: there was one major bleed with YM150 (60 mg) and one with enoxaparin.
Conclusions: The oral direct FXa inhibitor YM150 demonstrated a significant dose response regarding efficacy. Doses from 30 to 120 mg had comparable efficacy to enoxaparin, without compromising safety regarding major bleeding events.