title: Suboptimal response to clopidogrel: a genetic risk factor for recurrent ischaemic stroke.
abstract: Anti-platelet agents (APA) are widely used in the secondary prevention of ischaemic stroke but about 30% of patients derive suboptimal platelet inhibition from APA. An underlying cause for suboptimal platelet inhibition is varying response to clopidogrel, which is linked to polymorphisms in the CYP2C19 gene responsible for the metabolism and activation of clopidogrel. CYP2C19 polymorphism influences clinical outcomes in patients with coronary artery disease, particularly among those treated with percutaneous transluminal coronary artery stenting. Randomized controlled trials have shown that high doses of clopidogrel can overcome suboptimal platelet response in carriers of the CYP2C19(∗)2 allele. The United States Food and Drug Administration has issued a boxed warning advising clinicians to consider genotyping patients prior to prescribing clopidogrel. There are ongoing studies investigating the clinical utility of genotyping to inform management decisions in stroke prevention.
authors.affiliation: Department of Neurology, Royal Melbourne Hospital and University of Melbourne, Grattan Street, Parkville, Victoria 3050, Australia.
authors.forename: Daniel
authors.initials: D
authors.lastname: Bennett
authors.forename: Bernard
authors.initials: B
authors.lastname: Yan
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D004305:Dose-Response Relationship, Drug; D005838:Genotype; D006801:Humans; D007511:Ischemia / Q000150:complications; D010597:Pharmacogenetics; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D055502:Secondary Prevention; D020521:Stroke / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine