Clopidogrel Pharmacogenomics and Risk of Inadequate Platelet Inhibition: US FDA Recommendations

Abstract

Antiplatelet therapy with clopidogrel is the current standard of care for coronary artery disease patients undergoing a percutaneous coronary intervention. However, approximately 25% of patients experience a subtherapeutic antiplatelet response. Clopidogrel is a prodrug that undergoes hepatic biotransformation by CYP2C19 into its active metabolite. Several studies have reported that, compared with wild-type individuals, CYP2C19 variant allele carriers exhibit a significantly lower capacity to metabolize clopidogrel into its active metabolite and inhibit platelet activation, and are therefore at significantly higher risk of adverse cardiovascular events. Consequently, the US FDA has recently changed clopidogrel‘s prescribing information to highlight the impact of CYP2C19 genotype on clopidogrel pharmacokinetics, pharmacodynamics and clinical response. Future studies remain necessary to develop effective personalized therapeutic strategies for CYP2C19 variant allele carriers and other individuals at risk for clopidogrel nonresponsiveness.

KEYWORDS::

• clopidogrel
• CYP2C19
• FDA
• P-glycoprotein
• pharmacodynamics
• pharmacogenomics
• pharmacokinetics
• polymorphism
• proton-pump inhibitors

Financial & competing interest disclosure

Howard L McLeod is a consultant for Medco Health Solutions, Affymetrix and Myriad Genetics. 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.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

Howard L McLeod is a consultant for Medco Health Solutions, Affymetrix and Myriad Genetics. 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. No writing assistance was utilized in the production of this manuscript.