Antithrombotic prevention in vascular disease: bases for a new strategy in antithrombotic therapy

The hemostatic system is a physiological process to prevent hemorrhage and maintain a balance between clot formation and fluidity of blood in the circulation. After endothelial injury, platelets adhere to the exposed subendothelium and are activated by locally released agonists to stimulate thrombin formation [1], contributing to hemostatic control. Under other circumstances, such as in arterial disease, clots form upon atheroma rupture, primarily in connection with plaque conditions and in situ thrombin generation. After a clot starts to form, its growth depends on platelet recruitment and aggregation, concentration of thrombin at the surface of the clot, and changes in local blood flow. Thus, clot growth can be inhibited by blocking thrombus-bound thrombin activity and/or by inhibiting platelet function.Thrombin is the strongest platelet agonist, and inhibition of thrombin can also prevent platelet activation. In fact, any intervention singly directed at thrombin activity or platelet activation may simultaneously affect the other function [2].Aspirin (acetylsalicylic acid), and clopidogrel, are the mainstay antiplatelet therapies for arterial disease. Together with heparin, they constitute the first-line treatments for acute coronary disease. Clinical trials have established the benefit of aspirin for coronary prevention, and it is considered the gold standard for arterial antithrombotic therapy – despite its limitations with regard to preventing thrombosis.Coadministration of aspirin and clopidogrel enhances platelet inhibition, because these agents act through different platelet receptors; however, the benefit of combined antiplatelet treatment over aspirin alone in preventing thrombotic outcomes is debated [3-5].Therapies that include multiple drugs affecting primary hemostasis (antiplatelet drugs) or a combination of antiplatelets and anticoagulants, as in ischemic heart disease, are more aggressive than a single therapy. Combined antithrombotic treatment conf