Platelet-endothelial interactions in atherothrombotic disease: Therapeuticimplications

The role of the platelet and the endothelium in the pathogenesis of atheros clerosis and subsequent ischemic events has been the subject of extensive i nvestigation. Arterial sites where endothelial function is severely impaire d are often the sites of atheroma development. Lesion evolution impairs end othelial function, leading to a self-perpetuating cycle of growth. During e arly lesion development, overt thrombotic events are rare. However, rupture of an advanced, necrotic plaque or intimal ulceration triggers arterial th rombosis, at which point the importance of platelet function may be seen cl early. The Antiplatelet Trialists' Collaboration meta-analysis demonstrated the benefit of antiplatelet therapy to patients with atherosclerotic disea se. Aspirin is the most widely studied agent and is considered the standard of antiplatelet therapy. Newer agents that intervene at different stages o f the platelet activation pathway have been developed. Clopidogrel, a new a denosine diphosphate receptor antagonist, is more effective than aspirin in reducing vascular events in patients with prior myocardial infarction, str oke, or established peripheral arterial disease. The glycoprotein IIb-IIIa antagonists such as abciximab have proven effective in the setting of activ e arterial thrombosis and percutaneous revascularization, but their value i n secondary prevention remains unknown. All patients with atherosclerosis s hould be treated with an antiplatelet drug. Current evidence suggests that either aspirin or clopidogrel are appropriate first-line agents. There is u rgent need for an analysis of the risk/benefit ratio in various populations and clinical settings to determine the most appropriate type and intensity of therapy for a given patient.