Optimizing antiplatelet therapy in coronary interventions.

Percutaneous coronary intervention has had a dramatic impact on the current practice of cardiology. One of its important limitations, however, is the potential for producing unfavorable outcomes such as acute coronary closure following angioplasty or atherectomy or subacute thrombosis following stent implantation. These complications may lead to death, myocardial infarction, or the need for urgent bypass surgery. One mechanism underlying these clinical events is platelet-mediated thrombosis due to arterial trauma. Therapeutically, platelet activation by thromboxane and adenosine diphosphate (ADP), as well as platelet aggregation by glycoprotein IIb/IIIa (GPIIb/IIIa) receptors, has been inhibited with various pharmacologic agents. c7E3 (abciximab), a monoclonal antibody directed against GPIIb/IIIa, has been shown to have potent effects on reducing both acute and subacute complications. Other parenteral GPIIb/IIIa inhibitors, including peptide and small nonpeptide molecules, have also been found to be clinically effective. Oral versions of similar drugs are currently being evaluated, but several have resulted in disappointing efficacy and safety profiles and have failed to show advantages over aspirin. With all antiplatelet agents, in particular GPIIb/IIIa receptor inhibitors, bleeding and vascular complications must be addressed. Inhibition of thromboxane-induced platelet activation with aspirin has been standard therapy for angioplasty and in the global management of vascular disease. Newer agents that block ADP-mediated platelet activation, the thienopyridines, have been found to be synergistic to aspirin in their effects on the complications of coronary intervention. Ticlopidine and, more recently, clopidogrel, in conjunction with aspirin, have become standard therapies for preventing subacute thrombosis after stent implantation. Large-scale clinical trials are ongoing to optimize their use in combination with GPIIb/IIIa inhibitors.