Platelet reactivity and nonresponse to dual antiplatelet therapy: a review

Clopidogrel is a second-generation thienopyridine that irreversibly inhibits the P2Y(12) adenosine diphosphate (ADP) receptor on platelets, preventing platelet aggregation. As early as 2003, researchers have observed inter-patient variability in response to clopidogrel, leading to a multitude of studies investigating the phenomenon of "clopidogrel resistance," due to the possible link between clopidogrel resistance and in-stent thrombosis. However, due to differences in study methodology and the lack of a clear definition, there is confusion about what it means and its clinical implications. Literature searches were performed using the Web of Science Database. Keywords used to search for relevant literature included clopidogrel resistance. While several studies have shown associations between high platelet reactivity and a high incidence of adverse outcomes, the optimal level of platelet inhibition is unknown. Regardless of the term used to describe high platelet reactivity after treatment, evidence shows that this leads to adverse clinical outcomes. Future goals for research should be aimed at developing a standard method of measuring platelet function and investigating determinants of high platelet reactivity. Alternative treatment options for patients with high platelet reactivity in the face of dual antiplatelet therapy are currently being investigated.