Ximelagatran is a
direct thrombin inhibitor that offers numerous potential advantages compared with traditional
anticoagulants. It is given orally, has a rapid onset of action, does not require laboratory monitoring, and is not associated with immune-mediated
thrombocytopenia. Numerous phase III trials with
ximelagatran focusing on
deep vein thrombosis prophylaxis and treatment,
stroke prevention in patients with
atrial fibrillation, and
secondary prevention after acute
myocardial infarction have been conducted. Results of these trials indicate that
ximelagatran has similar efficacy and risk of
bleeding compared with currently used
anticoagulants. Accordingly, the potential of this agent to replace
warfarin therapy for a variety of indications has been widely touted.
Ximelagatran has already been approved in Europe for prophylaxis of
venous thromboembolism in patients undergoing hip or knee surgery. However, an adverse effect of
ximelagatran is liver
enzyme elevation, which has been observed in 5% to 10% of patients with chronic administration of the
drug. Although initially felt to be transient in nature, subsequent data presented to the Federal
Drug Administration suggest a small but real risk of significant hepatotoxicity. These data led the advisory committee to the Federal
Drug Administration to recommend against immediate approval of
ximelagatran pending further information. The consistent results of completed trials with
ximelagatran suggest that it has the potential to be used in many conditions that currently require treatment with
warfarin and
heparin products. The potential benefit that may be achieved by the replacement of these historically problematic narrow therapeutic index agents must be weighed against as yet undetermined long-term risks of hepatotoxicity.