The potential of genotype-guided antiplatelet therapy: promises and challenges

ABSTRACT

Introduction: Presence of loss-of-function (LoF) allele of CYP2C19 gene has been associated with poor clopidogrel active metabolite generation, poor antiplatelet response, and elevated risk for cardiovascular events in patients treated with coronary stenting. The utility of genetic testing to identify patients with CYP2C19 LoF allele and alternative strategies to overcome its limitations during clopidogrel therapy are the focus of recent translational research studies.

Areas covered: In this review, the authors discuss the relation of single nucleotide polymorphisms (SNPs) of CYP2C19 on clopidogrel pharmacology and their relation to clinical outcomes in coronary artery disease patients. They also discuss the methods available to assess CYP2C19 SNP’s, the current evidence available to support the genotype-guided antiplatelet therapy and its promises and challenges.

Expert commentary: There is a strong potential for genetic testing during clopidogrel therapy in patients undergoing coronary stenting and to personalize antiplatelet therapy. A point-of-care assay is more suitable to assess CYP2C19 LoF allele. The optimal strategy to overcome the influence of LoF carriage in patients treated with clopidogrel is either prasugrel or ticagrelor, although randomized studies assessing this approach have not been performed.

KEYWORDS:

• Platelet
• P2Y₁₂ receptor
• coronary stenting
• clopidogrel
• prasugrel
• ticagrelor
• CYP2C19
• genetic testing

Declaration of interest

P Gurbel reports receiving grants from the National Institutes of Health, Bayer, Medicure, Instrumentation labs, Haemonetics, Amgen, Idorisa, Ionis, Janssen, and Merck; receiving honoraria and payment for lectures, consultations including service on speaker’s bureaus from Bayer, Janssen, Merck, UptoDate and Medicure; and holding patents in the area of personalized antiplatelet therapy and interventional cardiology. U Tantry reports receiving honoraria from Astra Zeneca, UptoDate, and Medicure. 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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript has not been funded.