Current Evidence for Genetic Testing in Clopidogrel-Treated Patients Undergoing Coronary Stenting

Abstract

A combined dual antiplatelet treatment consisting of aspirin and the P2Y12 receptor inhibitor clopidogrel is still considered the standard of care treatment in most of the patients undergoing percutaneous coronary intervention (PCI). Numerous research studies during the last decade, however, have highlighted possible shortcomings of the oral antiplatelet agent clopidogrel, namely its large response variability resulting in an unpredictable response for the individual patient,1,2 the association of both a low3 or enhanced response4,5 with a worse clinical outcome and the dependency of individual responsiveness on nongenetic and genetic variables.6 Response by Pare and Eikelboom on p 513 Clopidogrel is a prodrug that requires bioactivation into its active thiol metabolite before it targets the P2Y12 receptor on blood platelets. In vivo bioactivation of the drug is a 2-step process that is closely linked to the cytochrome P450 (CYP) system. Different isoenzymes are responsible for clopidogrel bioactivation and among them the isoenzyme CYP2C19 was found to play a key role in this setting by contributing to both clopidogrel bioactivation steps.7 In this context, common genetic variants within the CYP2C19 gene have been the subject of considerable attention and have stimulated numerous research projects in recent years.8–14 Beyond CYP2C19, other genes involved in clopidogrel absorption, bioactivation or interplay with the blood platelet and their receptors have been associated with drug responsiveness and clinical outcome as well. Indeed, a growing body of evidence suggests a possible role of genotyping in patients undergoing coronary stenting with a view on optimizing response to P2Y12 receptor inhibitors during and after the procedure. We review available evidence on the need of individualizing antiplatelet treatment regimens in everyday clinical practice. ### Genetic Determinants for Clopidogrel Response and Clinical Outcome In recent years, multiple genetic factors within different candidate genes being involved in clopidogrel absorption, bioactivation, and …