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.