Development and Use of Platelet Glycoprotein Antagonists in Heart Disease

Platelets are not only responsible for primary hemostasis (1 ), but also for the thrombi that produce the morbidity and mortality of arterial vascular disease (2 ). Although considerable effort has been expended to associate augmented platelet function with arterial thrombosis, it is more likely that the formation of platelet thrombi simply represents normal platelet function in the wrong location. It follows then that a rational approach to treating atherosclerotic disease is to prevent the development of vascular lesions in the first place. Nonetheless, the administration of platelet-inhibitory drugs, such as aspirin (3 ), has been of proven benefit to individuals with established vascular disease, providing the impetus to identify more effective clinically useful platelet function inhibitors. Moreover, there has been substantial progress in understanding the biochemical basis of platelet function, providing additional targets for drug development. However, clinical experience has shown that the therapeutic index for the existing potent platelet inhibitors is narrow, suggesting that new and novel approaches to impairing platelet function will be required.