Platelets and new antiplatelet drugs

Rosemarie A Reiter and Bernd Jilma

Platelets play an important, live-saving role in hemostasis and blood clotting at sites of vascular injury. However, unwanted platelet activation and arterial thrombus formation are implicated in the onset of myocardial infarction (MI), stroke, and other cardiovascular diseases. Different mechanisms, such as vascular damage, the development of mural platelet thrombi as a response to injury, and the biochemical effects of intraplatelet substances that are released in response to damage may be involved. Thus, antiplatelet therapy has become a mainstay of treatment for these conditions and the benefit of antiplatelet drugs is documented across a wide spectrum of clinical conditions. Aspirin has been regarded as the prototype of antiplatelet drug and is still the most widely used agent. Aspirin’s antiplatelet effect is directly due to irreversible inactivation of arachidonic metabolism and suppression of thromboxane A2 (TXA2) synthesis. However, platelet activation occurs via several pathways that do not rely on amplification by released TXA2. Therefore a number of other compounds have been developed to complement the beneficial effect of aspirin. Four main classes of antiplatelet agents are currently available for clinical use: aspirin, the phosphodiesterase inhibitors, the thienopyridines, and the platelet glycoprotein αIIbβ3 (GPIIb/IIIa) receptor antagonists. This review discusses the state of the art of antiplatelet therapies and recent advances in antiplatelet therapies using aspirin as the reference standard.