Variability in platelet response to the antiplatelet agents aspirin and clopidogrel: mechanisms, measurement, and clinical relevance.

Platelet reactivity (eg, platelet adhesion, activation, aggregation) is the underlying pathology for atherothrombotic processes and subsequent ischemic complications. Antiplatelet drugs, including aspirin, dipyridamole, thienopyridines (clopidogrel and ticlopidine), and glycoprotein IIb/IIIa antagonists, have proven efficacy in atherothrombotic event prevention. However, variability of platelet response measured in the laboratory has been reported and is a subject of keen interest.It is unclear to what extent variability of platelet response to antiplatelet agents is associated with clinical outcomes. A better understanding of this issue requires a general consensus for a standard, preferably point-of-care, ex vivo or in vitro assay to determine the effects of antiplatelet agents on key platelet functions. Currently, results using various methods have not yielded an obvious answer. Small-scale studies have examined the correlation between ex vivo inhibition of platelet aggregation or residual platelet activity and clinical endpoints, and although evidence shows that such correlations may exist, results have not been consistent or definitive. Data from large-scale prospective trials are needed to expand our current understanding of the benefits and limitations of utilizing platelet function tests to effectively manage the balance between protection and risks associated with the antiplatelet therapies, aspirin, and clopidogrel.