Clinical applications of new antithrombotic agents

The clinical targets for which new generations of antithrombotics have been or are currently under clinical development are those associated with a high risk for thromboembolism, (a) patients undergoing general, orthopedic, major abdominal, and cancer surgery, to prevent venous thromboembolism; (b) patients with deep-vein thrombosis and/or pulmonary embolism who are at high risk for extension or recurrence of thromboembolism; (c) patients with unstable angina or myocardial infarction treated with percutaneous transfemoral coronary angioplasty, in whom antithrombotic treatment aims to prevent subsequent arterial thrombus formation and reocclusion. In most of these conditions standard heparin at prophylactic or therapeutic doses has proven to be only moderately effective. Furthermore, standard heparin has a rather poor bioavailability, a large and unpredictable variability in anticoagulant response, and a non-specific binding to many plasma proteins. Moreover, heparin treatment is associated with side effects such as bleeding, heparin-induced thrombocytopenia, and osteopenia. New antithrombotics have been designed which more specifically inhibit pivotal activated coagulation factors, i.e., Xa and IIa, and have potentially fewer undesired interactions and side effects. In this review we first provide an overview of recent insights on the mechanism of blood coagulation and the levels at which antithrombotics interfere with this system. Subsequently, we discuss specific new antithrombotic agents, and in particular the results of recent clinical investigations.