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. \ua9 2006 International Society on Thrombosis and Haemostasis