Current Evidence for Genetic Testing in Clopidogrel-Treated Patients Undergoing Coronary StentingResponse to Sibbing, Bernlochner and Kastrati

• Controversies in Interventional Cardiology

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

1. Dirk Sibbing, MD,
2. Isabell Bernlochner, MD and
3. Adnan Kastrati, MD

+ Author Affiliations

1. From the From Deutsches Herzzentrum München and 1. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München (D.S., I.B., A.K.), Munich, Germany.

1. Correspondence to Dirk Sibbing, MD, Deutsches Herzzentrum München, Lazarettstrasse 36, 80838 München, Germany. E-mail dirk@sibbing.net

Introduction

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 low ³ or enhanced response ^{4, 5} with a worse clinical outcome and the dependency of individual responsiveness on nongenetic and genetic variables. ⁶

Response by Paré 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 …

Current Evidence for Genetic Testing in Clopidogrel-Treated Patients Undergoing Coronary StentingResponse to Sibbing, Bernlochner and Kastrati