title: Clopidogrel response variability: impact of genetic polymorphism and platelet biomarkers for predicting adverse outcomes poststenting.
abstract: The aim of this study was to triage platelet reactivity and adverse vascular outcomes after dual antiplatelet therapy due to percutaneous coronary intervention (PCI) dependent on CYP2C19*2 and CYP2C19*3 genotypes in patients with coronary artery disease. Fifty-five patients with coronary artery disease were studied serially pre-PCI and post-PCI. Platelet reactivity was assessed by conventional light transmission aggregometry, VerifyNow Analyzer, and thromboelastography with platelet mapping. Genetic testing was performed with allele-specific real-time polymerase chain reaction. Adverse events included vascular death, acute myocardial infarction, repeated PCI, definite stent thrombosis, and angina recurrence. The common genotype (GG) was found in 39 patients, heterozygous polymorphism CYP2C19 (GA) G681A allele was detected in 14 patients, and the rare homozygous polymorphism CYP2C19 (AA) G681A allele was exhibited in 2 patients. There were no CYP2C19*3 (Trp212Ter) carriers among index patients. The platelet reactivity was higher in patients with heterozygous and homozygous carriers compared with GG genotype. The largest differences were observed among GG, GA, and AA genotypes, which correlated with the average values of platelet aggregation (P = 0.02). There was a significant link between adverse events and high platelet reactivity assessed by light transmission aggregometry (P = 0.002). We found a trend between different genotype and VerifyNow readings (P = 0.057); moreover, their cumulative impact on adverse events was significant (P = 0.041). Platelet reactivity is higher in patients with heterozygous and homozygous carriers of CYP2C19*2 versus common genotype and may predict an increased risk of clopidogrel response variability and/or experiencing adverse cardiac events.
authors.affiliation: 1Bakoulev Center for Cardiovascular Surgery, Department of Nonivasive Cardiology, Moscow, Russia; and 2HeartDrug™ Research Laboratories, Johns Hopkins University, Towson, MD.
authors.forename: Elena Z
authors.initials: EZ
authors.lastname: Golukhova
authors.forename: Mariya N
authors.initials: MN
authors.lastname: Ryabinina
authors.forename: Naida I
authors.initials: NI
authors.lastname: Bulaeva
authors.forename: Marina V
authors.initials: MV
authors.lastname: Grigorian
authors.forename: Maida Ch
authors.initials: MCh
authors.lastname: Kubova
authors.forename: Victor L
authors.initials: VL
authors.lastname: Serebruany
mesh_terms: D000368:Aged; D015415:Biomarkers; D001792:Blood Platelets / Q000187:drug effects*; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011110:Polymorphism, Genetic; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine