Fondaparinux sodium (
Arixtra;
fondaparinux) is the first of a new class of synthetic pentasaccharide
anticoagulants that bind to
antithrombin and inhibit the action of
factor Xa. In three large, well designed trials, subcutaneous
fondaparinux 2.5mg once daily was more effective than subcutaneous
enoxaparin sodium (
enoxaparin) 30 mg twice daily or 40 mg once daily at preventing
venous thromboembolism (VTE) at day 11 in patients undergoing hip replacement, elective major knee or hip fracture surgery; a fourth trial demonstrated similar efficacy to
enoxaparin 30 mg twice daily in hip replacement.
Fondaparinux recipients had a lower incidence of proximal
deep vein thrombosis (DVT) in two studies. In a meta-analysis of the four trials, patients receiving
fondaparinux had a >50% reduction in the relative risk of VTE at day 11.
Fondaparinux compared favourably with
enoxaparin in several pharmacoeconomic analyses. In a large, controlled trial in hip fracture patients, extended prophylaxis with
fondaparinux (duration 25-31 days) substantially reduced the incidence of VTE at day 25-32 compared with prophylaxis for 6-8 days, and was a cost-effective treatment strategy. Moreover, extended prophylaxis significantly decreased the rate of proximal, total and distal DVT and symptomatic VTE.
Fondaparinux was generally well tolerated in clinical trials in patients undergoing major orthopaedic surgery. However, following major knee surgery and in a meta-analysis of pooled data from four trials,
fondaparinux recipients had a significantly higher incidence of overt
bleeding with a
bleeding index > or =2, but no increase in fatal
bleeding,
bleeding into a critical organ or
bleeding leading to reoperation. The
bleeding risk is related to the timing of the first dose and when
fondaparinux was initiated between 6 and 8 hours after surgery, the
bleeding risk was similar to
enoxaparin. Extended prophylaxis with
fondaparinux was not associated with a significantly increased risk of
bleeding events. In conclusion,
fondaparinux is more effective than
enoxaparin at preventing postoperative VTE in patients undergoing elective hip replacement, major knee or hip fracture surgery. Extended
therapy with
fondaparinux considerably increases its efficacy without a significant increase in the incidence of
bleeding episodes.
Fondaparinux was generally well tolerated in clinical trials.
Fondaparinux is an effective and useful alternative to low molecular weight heparins for the prevention of VTE following major orthopaedic surgery.