The pharmacogenetic control of antiplatelet response: candidate genes and CYP2C19

Abstract

Introduction: Aspirin, clopidogrel, prasugrel and ticagrelor are antiplatelet agents for the prevention of ischemic events in patients with acute coronary syndromes (ACS), percutaneous coronary intervention (PCI) and other indications. Variability in response is observed to different degrees with these agents, which can translate to increased risks for adverse cardiovascular events. As such, potential pharmacogenetic determinants of antiplatelet pharmacokinetics, pharmacodynamics and clinical outcomes have been actively studied.

Areas covered: This article provides an overview of the available antiplatelet pharmacogenetics literature. Evidence supporting the significance of candidate genes and their potential influence on antiplatelet response and clinical outcomes are summarized and evaluated. Additional focus is directed at CYP2C19 and clopidogrel response, including the availability of clinical testing and genotype-directed antiplatelet therapy.

Expert opinion: The reported aspirin response candidate genes have not been adequately replicated and few candidate genes have thus far been implicated in prasugrel or ticagrelor response. However, abundant data support the clinical validity of CYP2C19 and clopidogrel response variability among ACS/PCI patients. Although limited prospective trial data are available to support the utility of routine CYP2C19 testing, the increased risks for reduced clopidogrel efficacy among ACS/PCI patients that carry CYP2C19 loss-of-function alleles should be considered when genotype results are available.

Keywords:

• antiplatelet agents
• aspirin
• candidate genes
• clopidogrel
• CYP2C19
• pharmacogenetics
• pharmacogenomics
• prasugrel
• ticagrelor

Declaration of interest

JP Lewis receives support from NIH for antiplatelet pharmacogenomics research. J-S Hulot has received research grant support from Biotronik, and consulting fees from Daiichi Sankyo. SA Scott receives support from NIH for antiplatelet pharmacogenomics research and is an Associate Director of a clinical laboratory that performs CYP2C19 testing. This research was supported in part by the National Institute of General Medical Sciences (NIGMS) of the National Institutes of Health (NIH), through grants K23 GM102678 (J.P.L.) and K23 GM104401 (S.A.S.). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Notes

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