New therapeutic option for thromboembolism – dabigatran etexilate

Abstract

Background: Thrombin plays a key role in blood coagulation and haemostasis; thus its inhibition has been identified as a reasonable target to block the coagulation cascade. Direct thrombin inhibitors are potential prophylactic agents for venous thromboembolism and arterial thrombosis, which often accompany operative procedures and cardiac disease, especially orthopedic surgery and atrial fibrillation, respectively. New orally available anticoagulant agents with a wide therapeutic window are keenly anticipated because warfarin and heparins have some disadvantages, and recent progress in pharmaceutical techniques has led to the development of orally administered direct thrombin inhibitors. Objectives: In this review, we discuss the usefulness of dabigatran etexilate as a new therapeutic option for preventing thromboembolism, including chemistry, pharmacokinetics, and pharmacodynamics, from the results of recent clinical studies. Methods: We systematically focused on relevant published studies, as data from recent clinical studies were difficult to obtain owing to their ongoing status. Conclusions: Dabigatran etexilate is a promising new oral anticoagulant that offers greatly expanded therapeutic options for both patients and physicians.

Keywords::

• anticoagulants
• dabigatran etexilate
• direct thrombin inhibitors
• thromboembolism
• thromboprophylaxis

7. Conclusion

Dabigatran etexilate is a promising new oral anticoagulant that offers definite options for thromboprophylaxis strategies. Since its efficacy and safety have been proven in Phase III studies, the drug is considered very useful for the prophylaxis and treatment of VTE. Although patients who receive treatment for a long period must be investigated further, DTIs including dabigatran etexilate are likely to take a central role in antithrombotic therapy beyond heparins and warfarin.

Figure 1. Multiple functions of thrombin in coagulation cascade and with platelets. The tissue factor pathway initiates coagulation, triggering the tissue factor/activated factor VIIa (TF/VIIa) complex, which activates factors IX and X. Activated factor IX (IXa) propagates coagulation by activating factor X with activated factor VIII (VIIIa). Furthermore, activated factor X (Xa) converts prothrombin to thrombin in cooperation with activated factor V (Va) as a cofactor. Thrombin also activates factors V, VIII, and XI. This positive feedback accelerates the production of thrombin, which plays a central role in a common pathway to promote fibrin formation. Platelet activation is mediated by PARs on platelets.

Figure 2. Chemical structure of dabigatran etexilate.

Table 1. Summary of double-blind, randomized studies of dabigatran etexilate.