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Systematic review
Carrying one or two reduced-function CYP2C19 alleles is associated with an increased risk of major adverse cardiovascular events in people undergoing percutaneous coronary intervention and treated with clopidogrel
  1. Andrea H Ramirez1,
  2. Jessica T Delaney1,
  3. Alan R Shuldiner2
  1. 1Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
  2. 2Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA
  1. Correspondence to Alan R Shuldiner
    Division of Endocrinology, Diabetes and Nutrition, 660 West Redwood Street, Room 494, Baltimore, MD 21201, USA; ashuldin{at}

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The antiplatelet effect of clopidogrel varies among users as measured by ex vivo platelet function studies and clinical outcomes. Studies have identified common reduced-function variants in the cytochrome P450 enzyme gene, CYP2C19, that are associated with clopidogrel responsiveness. The fully functional form of the gene, designated CYP2C19*1, metabolises clopidogrel from its native prodrug state to its active antiplatelet metabolite more efficiently than CYP2C19*2, found commonly in Caucasians, African Americans and Asians, and CYP2C9*3, common only in Asians. Individuals carrying one of these reduced-function alleles are intermediate metabolisers, whereas those carrying two reduced-function alleles are poor metabolisers. In patients on clopidogrel, these variants have been associated with poorer clinical outcomes in many studies, although not all have shown an effect, particularly in patients with one reduced-function allele.


Relevant studies for this meta-analysis were gathered with a combination of computer database searches and expert consultation. Of the 31 possible studies, 9 met the inclusion criteria of patients predominantly invasively managed with percutaneous coronary intervention (PCI) and with …

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  • Competing interests ARS receives grant support from the National Institutes of Health to study the pharmacogenomics of antiplatelet agents. ARS is also a consultant for Bristol-Myers Squibb/Sanofi-aventis. AHR and JTD have no competing interests.