Oral, direct Factor Xa inhibition with BAY 59-7939 for the prevention of venous thromboembolism after total hip replacement

Background: Joint replacement surgery is an appropriate model for dose-ranging studies investigating new anticoagulants. Objectives: To assess the efficacy and safety of a novel, oral, direct factor Xa (FXa) inhibitor - BAY 59-7939 - relative to enoxaparin in patients undergoing elective total hip replacement. Methods: In this double-blind, double-dummy, doseranging study, patients were randomized to oral BAY 59-7939 (2.5, 5, 10, 20, or 30 mg b.i.d.), starting 6-8 h after surgery, or s.c. enoxaparin 40 mg once daily, starting on the evening before surgery. Treatment was continued until mandatory bilateral venography was performed 5-9 days after surgery. Results: Of 706 patients treated, 548 were eligible for the primary efficacy analysis. The primary efficacy endpoint was the incidence of any deep vein thrombosis, non-fatal pulmonary embolism, and all cause mortality; rates were 15%, 14%, 12%, 18%, and 7%for BAY 59-7939 2.5, 5, 10, 20, and 30 mg b.i.d., respectively, compared with 17% for enoxaparin. The primary efficacy analysis did not demonstrate any signi.cant trend in dose-response relationship for BAY 59-7939. The primary safety endpoint was major, postoperative bleeding; there was a significant increase in the frequency of events with increasing doses of BAY 59-7939 (P = 0.045), but no signi.cant di.erences between individual BAY 59-7939 doses and enoxaparin. Conclusions: When eficacy and safety were considered together, compared favorably with enoxaparin for the prevention of venous thromboembolism in patients undergoing elective total hip replacement. © 2006 International Society on Thrombosis and Haemostasis.