Anticoagulant therapy plays an important role in the prevention and treatment of pathologic arterial and
venous thrombosis. There is increasing enthusiasm in the inhibition of
Factor Xa as a target to achieve therapeutic anticoagulation because of its central and 'upstream' position in the coagulation process. The indirect, selective, parenteral
Factor Xa inhibitor fondaparinux sodium (synthetic pentasaccharide) has been studied extensively in the prevention and treatment of
venous thromboembolism. In an overview of four studies in patients undergoing major
orthopedic surgery,
fondaparinux sodium was associated with a 55% reduction in recurrent
thromboembolism, albeit with a modest increase in
bleeding. Preliminary results from phase II studies of
fondaparinux sodium in patients with ST-elevation and non-ST-elevation
acute coronary syndromes have been promising and have led to the initiation of two large phase III trials, which are currently underway.
Idraparinux sodium, a long-acting synthetic pentasaccharide, is currently being investigated as a once-weekly alternative to other long-term
anticoagulants.
DX-9065a and
razaxaban are two of many direct selective
Factor Xa inhibitors currently in development.
DX-9065a has been studied in phase II trials in patients undergoing
percutaneous coronary intervention and in those with non-ST-elevation
acute coronary syndromes.
Razaxaban has been studied in a phase II trial in patients who have undergone
orthopedic surgery. Data from these trials, although preliminary and based on small numbers of patients, suggest that direct selective
Factor Xa inhibition may provide effective anticoagulation, perhaps without excessive
bleeding. Inhibition of
Factor Xa is a promising target for the prevention and treatment of
thrombosis in both the venous and arterial circulation. Ongoing investigation with numerous oral and parenteral inhibitors of
Factor Xa will establish the potential of
Factor Xa as a target for therapeutic anticoagulation.