Role of platelet inhibitor therapy in myocardial infarction

Summary Atherosclerotic plaque disruption is the predominant pathogenetic mechanism underlying the acute coronary syndromes. Plaque rupture leads to the exposure of collagen and vessel media, resulting in platelet and clotting activation, and occlusive thrombus formation. While drugs that interfere with platelet activation and function have been available for years, more powerful agents with novel mechanisms of action are being developed. Of the available platelet inhibitor drugs, only aspirin, sulfinpyrazone, and dipyridamole have undergone extensive clinical testing in patients with cardiovascular disease. More recently ticlopidine, a new and potent platelet inhibitor, has been successfully tested in patients with coronary and vascular disease.In acute myocardial infaction, aspirin significantly reduces cardiovascular mortality and reinfarction. Furthermore, the combination of aspirin and a thrombolytic agent produces maximal benefit. A role for heparin in the prevention of early mortality and reinfaction is emerging. This drug is effective for the prevention of left ventricular thrombosis in patients with anterior myocardial infarction.In the secondary prevention of reinfarction and cardiovascular mortality, available data support the use of a platelet inhibitor. Trials have shown that aspirin is as effective alone as in combination with dipyridamole, and is probably more effective than sulfinpyrazone. Long-term anticoagulant therapy also appears to be beneficial, but is associated with a high cost, need for extensive monitoring, and potential for hemorrhagic side effects.The role of aspirin in primary prevention is controversial. It may be indicated for patients at high risk for coronary disease in whom the benefit of therapy may outweigh the potential risk of cerebral bleeding.Coronary atherosclerotic plaque rupture, associated with thrombus formation, is fundamental to the development of acute myocardial infarction. Based on this concept, the role of antithrombotic therapy for the prevention or treatment of ischemic events in patients with coronary artery disease has stimulated enormous interest among clinicians and basic investigators. In this review we will examine: a) the pathogenesis of coronary thrombosis, b) the pharmacology of plateletinhibitor agents, and c) their role in the management of patients with acute myocardial infarction and in primary and secondary prevention of cardiovascular disease.Platelets interact with both the coagulation and fibrinolytic systems in the pathogenesis of thrombosis. While the purpose of this review is to discuss the role of platelets and platelet inhibitors in coronary disease, the use of anticoagulant or thrombolytic agents will be analyzed briefly when pertinent.