ABSTRACT
Thrombotic events contribute significantly to the morbidity, mortality, and health
care costs of patients undergoing major orthopedic surgery. Despite therapy with unfractionated
heparin, low-molecular-weight heparin, or warfarin, thrombotic events continue to
occur at an unacceptably high rate in populations at risk. The need for improved prophylaxis
against venous thromboembolism has resulted in the development of several new antithrombotics,
both recently approved and investigational, that target specific steps in the hemostatic
pathway. These include direct thrombin inhibitors, agents that inhibit the factor
VIIa-tissue factor complex, and selective factor Xa inhibitors. Fondaparinux is the
first of the selective factor Xa inhibitors. It was evaluated in the most comprehensive
drug development program ever in major orthopedic surgery, culminating in four phase
III trials involving more than 7000 enrollees, and is the first agent in its class
to be approved by the U.S. Food and Drug Administration and the European Agency for
the Evaluation of Medicinal Products. It has been suggested that fondaparinux's superior
efficacy may be related to its ability to initiate selective inhibition of factor
Xa and its predictable linear pharmacokinetics.
KEYWORDS
Antithrombotics - deep vein thrombosis - fondaparinux - orthopedic surgery - venous
thromboembolism
