The major clinical indication for antiplatelet therapy has been the prevention of arterial thrombosis. Arterial thrombi are composed of predominantly platelets formed under conditions of elevated shear stress at sites of atherosclerotic vascular injury and disturbed blood flow. Aspirin, the prototype antiplatelet agent, has been in clinical use as an antithrombotic for almost a half century. However, clinical trials have exposed the limitations of aspirin, and there has been considerable recent progress in the development of more effective antiplatelet agents. These newer agents are rationally based on interrupting specific sites in the sequence of platelet activation. Inhibitors of the initial step of platelet adhesion remain experimental. Inhibitors of specific platelet agonist-receptor interactions include antithrombins, thromboxane A2 receptor antagonists, and adenosine diphosphate (ADP) receptor blockers including ticlopidine and clopidogrel. Inhibitors of arachidonic acid metabolism and thromboxane A2 include omega-3 fatty acids, aspirin and other nonsteroidal antiinflammatory drugs that inhibit cyclooxygenase, and thromboxane synthase inhibitors. The clinical efficacy of many of these agents may be limited by their actions, which are restricted to single, specific platelet receptors or metabolic pathways. Global interruption of the final step of platelet aggregation can be achieved with monoclonal antibodies and RGD (arginine-glycine-aspartic acid) analogs that block ligand binding to the platelet glycoprotein IIb/IIIa complex. Initial clinical trials with these novel agents have demonstrated superior efficacy in preventing reocclusion and restenosis following coronary angioplasty and atherectomy.
