Fondaparinux sodium: a review of its use in the prevention of venous thromboembolism following major orthopaedic surgery.

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.