title: Clopidogrel Resistance: case reports of CYP2C19 gene variants in suspected coronary stent thrombosis.
abstract: Clopidogrel is a widely used anti-platelet agent for the prevention of arterial thrombosis. Clopidogrel is administered as a pro-drug and metabolised to its active metabolite by the hepatic cytochrome P450 2C19 (CYP2C19) enzyme. The active metabolite is responsible for the anti-platelet activity of clopidogrel. Recent studies demonstrate that single nucleotide polymorphisms, (SNP's), in the gene for CYP2C19 result in significantly reduced production of the active metabolite of clopidogrel. Additional studies demonstrate that patients with SNP's in the CYP2C19 gene, including CYP2C19*2,*3,*4, and *5, have reduced production of the active metabolite of clopidogrel, reduced inhibition of platelet aggregation and increased incidence of coronary, cerebrovascular, and coronary stent thrombosis. We have been interested in determining the CYP2C19 genotype in cases of coronary stent thrombosis whilst on clopidogrel treatment and provide two case reports of coronary stent thrombosis whilst taking clopidogrel with subsequent CYP2C19 genotyping. As patients at risk of atherothrombosis in general, and stent thrombosis in particular, may be receiving or considered for anti-platelet therapy including clopidogrel, genotyping for CYP2C19 SNP's may be of benefit in the selection of appropriate anti-platelet therapy.
authors.affiliation: Department of Cardiology, Epworth Hospital, Richmond, Melbourne, Australia. drrjdick@bigpond.net.au
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Dick
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Dear
authors.forename: Keith A
authors.initials: KA
authors.lastname: Byron
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases; D000077144:Clopidogrel; D023921:Coronary Stenosis / Q000235:genetics / Q000628:therapy; D065731:Cytochrome P-450 CYP2C19; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics / Q000628:therapy; D010974:Platelet Aggregation / Q000187:drug effects / Q000235:genetics; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D020641:Polymorphism, Single Nucleotide; D015607:Stents; D013927:Thrombosis / Q000209:etiology / Q000235:genetics* / Q000628:therapy*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine