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Keywords:

  • direct factor Xa inhibitor;
  • oral anticoagulant;
  • prophylaxis;
  • total hip replacement;
  • venous thromboembolism;
  • YM150

Summary. Background: YM150, a new oral direct factor Xa inhibitor is used as prophylaxis for venous thromboembolism (VTE), a well-known risk after orthopaedic surgery. Objectives: To assess the safety and efficacy of thromboprophylaxis with YM150 in a dose escalation study. Patients/methods: Patients (174) undergoing hip replacement surgery were randomized per cohort to oral once daily YM150 or subcutaneous enoxaparin (40 mg daily) in a 4:1 ratio for 7–10 days treatment. The YM150 doses were 3, 10, 30 and 60 mg by sequential four-dose escalation cohorts. The primary endpoint was major and/or clinically relevant non-major bleeding. The incidence of VTE was defined as a composite of verified symptomatic events and/or positive findings at bilateral venography on the last treatment day. An independent adjudication committee evaluated blindly the outcomes of the open-label study. Results: No major and three clinically relevant non-major bleeds were reported, 1 (2.9%; 95% CI, 0.1–15.1) in the 3 mg and 2 (5.7%; 95% CI, 1.0–18.8) in the 10 mg YM150 dose groups. Of 147 patients (84%) with an evaluable venogram, VTE was observed in 51.9% (95% CI, 31.9–71.4), 38.7% (95% CI, 22.6–57.0), 22.6% (95% CI, 9.7–39.4), and 18.5% (95% CI, 7.5–36.5) in the YM150 dose groups 3, 10, 30 and 60 mg, respectively. A significant YM150 dose-related trend in VTE incidence was found (P=0.006). VTE with enoxaparin was 38.7% (95% CI, 22.6–57.0). Conclusions: YM150, 10–60 mg daily, starting 6–10 h after primary hip replacement, was shown to be safe, well tolerated and effective.