Role of Platelets and Antiplatelet Therapy in Cardiovascular Disease

Platelets have a key role in normal hemostasis and in the pathogenesis of atherothrombotic events, such as acute coronary syndrome. Following plaque rupture, platelets adhere to the subendothelial matrix, become activated and then aggregate to form a prothrombotic surface that promotes clot formation and subsequently vascular occlusion. Multiple pathways are involved in platelet activation, including those activated by adenosine diphosphate (ADP), thromboxane A2, epinephrine, serotonin, collagen, and thrombin. Currently, two groups of inhibitors of platelet activation are approved for clinical use in patients with acute coronary syndromes: cyclooxygenase-1 inhibitors, namely aspirin, and oral ADP receptor antagonists such as clopidogrel. These agents have shown improved short- and long-term clinical outcomes but are associated with increased bleeding risk, and the rates of recurrent ischemic events remain high. These considerations underscore the need for novel antiplatelet agents that can provide greater reduction in recurrent atherothrombotic events without increasing the risk of bleeding. Several novel antiplatelet agents are currently under clinical development, such as more potent ADP receptor antagonists and protease-activated receptor-1 antagonists. This article provides an overview of the basic principles of platelet biology and the current status of knowledge on available oral antiplatelet therapy, as well as those under clinical development.