Antiplatelet therapies: from aspirin to GPIIb/IIIa-receptor antagonists and beyond.
This review discusses recent advances in antiplatelet therapies, comparative analysis between the antiplatelet/ antithrombotic efficacy of various antiplatelet strategies and that of platelet glycoprotein GPIIb/IIIa-receptor antagonists, issues in the development of chronic anti-GPIIb/IIIa-receptor therapy and potential adjunct strategies using GPIIb/IIIa-receptor antagonists. Acute coronary syndromes are secondary to unstable angina, ST-segment elevation, and acute myocardial infarction. These involve the rupture of a vulnerable atherosclerotic plaque, leading to platelet adhesion, activation and aggregation at the site of rupture. Several studies suggest that complex or ulcerated plaques, which might promote further thrombotic events, can persist for more than one month after the acute event. These data suggest the potential added benefit of chronic oral therapy with antiplatelet drugs beyond the well-documented benefit of acute intravenous use of various GPIIb/IIIa-receptor antagonists. However the efficacy-safety ratio or the risk-benefit ratio for chronic oral antiplatelet therapy needs to be defined. Both aspirin and clopidogrel are available for chronic oral use. By contrast, there are tremendous challenges ahead with the oral GPIIb/IIIa-receptor antagonists because of their lack of expected benefit over aspirin. However, much still remains to be defined with regard to the optimization of current and future antiplatelet therapies or their optimized combinations.
Mousa
SA
DuPont Pharmaceuticals Co., Wilmington, DE 19880, USA.