New direct thrombin inhibitors

  • Alessandro Squizzato
  • Francesco Dentali
  • Luigi Steidl
  • Walter Ageno
IM - Review


Direct thrombin inhibitors (DTIs) are a class of anticoagulants that bind selectively to thrombin and block its interaction with its substrates. Dabigatran etexilate and AZD0837, the new generation of DTIs, are now under intense development, and are potentially of great interest for internists. Dabigatran etexilate is a potent, non-peptidic small molecule that specifically and reversibly inhibits both free and clot-bound thrombin by binding to the active site of thrombin molecule. It has been already licensed in the European Union and in Canada for the prevention of VTE in patients undergoing hip- and knee-replacement surgery. Ongoing trials are evaluating its efficacy and safety for the treatment of deep venous thrombosis and pulmonary embolism, primary and secondary prevention of VTE, prevention of systemic embolism in patients with non-valvular atrial fibrillation, and prevention of cardiac events in patients with acute coronary syndromes. AZD0837 is the prodrug of ARH06737, a potent, competitive, reversible inhibitor of free and fibrin-bound thrombin. At present, only limited, preclinical, phase I and phase II clinical data have been presented. The drug has now entered a phase III clinical program in the population of patients with atrial fibrillation. Their properties and the oral administration render these compounds, theoretically, more convenient than both vitamin K antagonist and low molecular weight heparins. However, only reports from clinical practice patterns over the next months and years will tell us how and when to use the new DTIs.


Anticoagulants Thrombin inhibitors Dabigatran Venous thromboembolism Atrial fibrillation 



The authors did not receive any financial support to write this manuscript.

Conflict of interest statement

The authors declare that they have no conflict of interest related to the publication of this manuscript.


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Copyright information

© SIMI 2009

Authors and Affiliations

  • Alessandro Squizzato
    • 1
    • 2
  • Francesco Dentali
    • 1
  • Luigi Steidl
    • 1
  • Walter Ageno
    • 1
  1. 1.Department of Clinical MedicineUniversity of InsubriaVareseItaly
  2. 2.U.O. Medicina I, Ospedale di CircoloVareseItaly

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