Assessment, Mechanisms, and Clinical Implication of Variability in Platelet Response to Aspirin and Clopidogrel Therapy

Antiplatelet therapy is the mainstay of treatment for patients with cardiovascular disease. However, some patients experience adverse cardiac events despite treatment with single- or dual-antiplatelet (aspirin and clopidogrel) therapy. Some of those events could be caused by low responsiveness to aspirin or clopidogrel. The frequency of this phenomenon has been reported to range from 1% to 45% for the 2 drugs. This wide range arises from the lack of a "gold-standard" definition to assess antiplatelet drug response and differences in assays, agonist concentrations, and cut-off points. Regardless of the variability in the incidence of aspirin or clopidogrel low responsiveness, several studies have indicated a clear relation between clopidogrel or aspirin low responsiveness and cardiovascular events. The evidence for an association between adverse clinical events and the results of ex vivo platelet function tests is stronger for clopidogrel than for aspirin. Currently, there is no established therapeutic approach for managing low response to aspirin or clopidogrel that has been shown in large trials to have clinical benefit. This review focuses on laboratory testing of antiplatelet response to aspirin and clopidogrel, the prevalence of low response, potential mechanisms, clinical significance, and prognostic value of this phenomenon and alternative approaches to optimize treatment in patients with low response to the drugs.