[Future potential indications for an oral thrombin inhibitor].
By the use of conventional anticoagulants, significant improvements were achieved in all fields of medicine. Although efficacious and widely used, their use is limited in several respects. In particular, the use of vitamin K antagonists is restricted in the clinical routine setting. The main reasons are the delayed on- and off-set of action, the narrow therapeutic window, the necessity of individual laboratory-controlled dosing, and interactions with food ingredients and drugs. The search for new antithrombotics with an improved safety/efficacy profile led to the development of the direct oral thrombin-inhibitor ximelagatran. It can be administered without routine monitoring of coagulation parameters and does not possess any of the previously mentioned limitations. The results from clinical phase II studies obtained so far are very encouraging. After completion of the clinical development program focussing on prevention and treatment of venous thromboembolism, on stroke prevention in atrial fibrillation and on acute coronary syndromes, it is desirable to continue with investigations with regard to long-term prophylaxis in high risk surgery, in chronic peripheral artery disease, in patients with left ventricular thrombi, artificial heart valves, or thrombophilia, as an alternative anticoagulant in heparin induced thrombocytopenia and for prevention of thromboembolic complications in oncology. Because of the mitogenic effects of thrombin on the proliferation of tumour cells, additional experimental studies aiming at a potential inhibition of thrombin-triggered oncogenesis is of uttermost interest.
Haas
S
S
Institut für Experimentelle Onkologie und Therapieforschung, Technische Universität München, Germany. sylvia.haas@lrz.turn.de
D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage / Q000592:standards / Q000627:therapeutic use*; D000991:Antithrombins / Q000008:administration & dosage / Q000592:standards / Q000627:therapeutic use*; D001384:Azetidines / Q000008:administration & dosage / Q000627:therapeutic use; D001596:Benzylamines; D006801:Humans; D011355:Prodrugs / Q000008:administration & dosage / Q000627:therapeutic use; D012449:Safety; D020521:Stroke / Q000517:prevention & control*; D013923:Thromboembolism / Q000517:prevention & control*
D000925:Anticoagulants; D000991:Antithrombins; D001384:Azetidines; D001596:Benzylamines; D011355:Prodrugs; C426686:ximelagatran