Variable Interindividual Responses to Antiplatelet Therapies – Do They Exist, Can We Measure Them, and Are They Clinically Relevant?

Abstract

Many patients suffer thrombotic events such as myocardial infarction, stroke and peripheral embolism despite therapy with recommended doses of all currently approved antiplatelet agents. Researchers have suggested that a subset of patients may be resistant to the antiplatelet effects of aspirin, and have developed substantial evidence to support this theory. The thienopyridines ticlopidine and clopidogrel and the glycoprotein IIb/IIIa inhibitors also exhibit substantial interpatient variability in the level of platelet inhibition they achieve. There are several biochemical factors that may contribute to the etiology of individual resistance to antiplatelet medications. Some studies suggest that the variability in patient responsiveness to these drugs may have clinical consequences, and data from trials evaluating clinical end points are needed to further elucidate this correlation.

Current status and prospects of antiplatelet therapy in percutaneous coronary intervention in Japan: Focus on adenosine diphosphate receptor inhibitors

“…Increasing the dosage of clopidogrel might be expected to overcome poor clinical response. However, this is not uniformly supported by results of clinical trials indicating that targeting an independent pathway may offer a more effective approach than attempting to overload an ineffective system [43].…”

Glycoprotein IIb/IIIa antagonists - from bench to practice

“…This degree of receptor occupancy is associated with a median ADP-induced platelet aggregation response of < 10 % of baseline [81 -83]. During the course of the infusion, the extent of inhibition in most patients declines gradually and the consistency of inhibition becomes less uniform, perhaps due to the emergence of the platelet a granule storage pool of receptors [84,85]. Nevertheless, at the completion of the 12-h infusion, most patients continue to have > 80 % receptor occupancy, and the median platelet aggregation is ~20 % of baseline [81 -83, 86].…”