ABSTRACT
Current strategies for the treatment and prevention of venous thrombosis require a mix of
parenteral and oral therapies that frequently require laboratory monitoring. Oral-direct thrombin
inhibitors have the potential to simplify antithrombotic therapy; these agents produce a
predictable anticoagulant response so that laboratory monitoring may be unnecessary. Ximela-
gatran, the oral direct thrombin inhibitor in the most advanced stage of development, is a prodrug
of melagatran, an active-site-directed inhibitor of thrombin. In phase II studies, ximelagatran has
been evaluated as thromboprophylaxis in patients undergoing elective hip or knee replacement
surgery and in patients with nonvalvular atrial fibrillation. The drug has also been studied in
patients with acute venous thrombosis. In each case, ximelagatran appears to be at least as safe
and effective as current antithrombotic interventions. Phase III studies with ximelagatran for
these indications are currently underway. If ximelagatran lives up to its initial promise, it has the
potential to revolutionize the prevention and treatment of thrombosis.
