Emerging options for thromboprophylaxis after orthopedic surgery: a review of clinical data.

In four randomized, controlled studies of patients undergoing orthopedic surgery, the antithrombotic efficacy and safety of subcutaneous fondaparinux 2.5 mg once/day were compared with those of subcutaneous enoxaparin regimens that were approved by the United States Food and Drug Administration. In patients undergoing elective hip replacement surgery, fondaparinux significantly reduced the frequency of venous thromboembolism (VTE). However, in a second trial that compared fondaparinux with enoxaparin 30 mg twice/day beginning 12-24 hours after surgery, a 26% risk reduction in favor of fondaparinux was not statistically significant. In patients undergoing elective knee replacement surgery, fondaparinux significantly reduced the risk of VTE compared with enoxaparin without increasing the risk of clinically relevant bleeding, although the risk of major bleeding defined by the bleeding index was significantly higher with fondaparinux. Fondaparinux was superior to enoxaparin 40 mg once/day in the setting of hip fracture surgery, with no increased risk of major bleeding. Meta-analysis of the four studies confirms the superior antithrombotic efficacy of fondaparinux over enoxaparin in orthopedic surgery and suggests that the risk of major bleeding is similar to that of enoxaparin when the first dose of fondaparinux is given at least 6 hours after surgery.