The Role of Oral Direct Thrombin Inhibitors in the Treatment of Venous Thromboembolism

Abstract

Unfractionated heparin and warfarin have been the mainstay of treatment of venous thromboembolism (VTE) for approximately half a century. However, both agents are difficult to dose accurately, require frequent blood testing and dosage adjustment, and can cause serious adverse effects. Oral direct thrombin inhibitors may provide more predictable anticoagulation with oral dosing, without the need for frequent blood test monitoring and without the adverse effects seen with conventional agents. The oral direct thrombin inhibitor closest to being marketed is ximelagatran, which has been through phase III trials. Available data thus far suggest that the efficacy and safety of this agent may allow it to replace both heparin (and low-molecular-weight heparin) and warfarin for VTE treatment and long-term prophylaxis. Concerns about ximelagatran that require further study are a 5-9% rate of transient elevation in liver enzyme levels, drug interactions, how patient adherence can be ensured in the absence of blood tests, and whether alterations in renal or hepatic function will require dosage adjustments. Although there is more to learn about ximelagatran, available data suggest that it is likely to be the most significant therapeutic advance in this area in over 50 years.