Antiplatelet Therapy in Coronary Disease: What Agent to Use,When, and How?

The striking efficacy of aspirin in preventing the thrombotic complications associated with cardiovascular diseases has stimulated the development and clinical evaluation of a new antiplatelet therapy. Some of the new agents are less effective than aspirin and others are as effective, or slightly better in certain circumstances. Many new antiplatelet agents interfere with platelet function by mechanisms other than inhibition of cyclooxygenase. Selective inhibition of thromboxane synthase, and/or thromboxane receptor, and infusion of prostacyclin or analogues have not resulted in benefits superior to those of aspirin. Ticlopidine and clopidogrel provide an alternative pathway to inhibit platelet aggregation and are very effective drugs. The benefits derived from interventions targeting different pathways to platelet aggregation stress a potential for added benefits with combination of various drugs. Platelet aggregation can now be inhibited by occupying the GPIIb/IIIA receptor with pharmacological agents preventing part or all fibrinogen binding to the receptor. The use of abciximab, an antibody against the receptor, has resulted in a significant reduction of the acute complications associated with coronary angioplasty. The antibody is not specific against the receptor versus other synthetic peptidic and nonpeptidic compounds that have been developed, widening the spectrum of potential interventions. The antibody and the new agents are now being evaluated in unstable angina and myocardial infarction. Orally active inhibitors are also under development, extending the range of clinical investigation to secondary prevention of acute coronary syndromes. Other promising approaches include inhibition of platelets interaction with endothelium and with leukocytes, and inhibition of active platelet secretion products.