title: Defining predictive values using three different platelet function tests for CYP2C19 phenotype status on maintenance dual antiplatelet therapy after PCI.
abstract: Published data suggests that the presence of CYP2C19*2 or *3 loss of function (LOF) alleles is indicative of increased platelet aggregation and a higher risk of adverse cardiovascular events after clopidogrel administration. We sought to determine cut-off values using three different assays for prediction of the CYP2C19 phenotype in Korean percutaneous coronary intervention (PCI) patients. We enrolled 244 patients with drug-eluting stent implantation who were receiving clopidogrel and aspirin maintenance therapy for one month or more. Platelet reactivity was assessed with light transmittance aggregometry (LTA), multiple electrode aggregometry (MEA) and the VerifyNow P2Y12 assay (VN). The CYP2C19 genotype was analyzed by polymerase chain reaction (PCR) and snapshot method. The frequency of CYP2C19 LOF allele carriers was 58.6%. The cut-off values from LTA, MEA and VerifyNow for the identification of LOF allele carriers were as follows: 10 µM ADP-induced LTA ≥ 48 %, VN>242 PRU and MEA ≥ 37 U. Between the three tests, correlation was higher between LTA vs. VN assays (r=0.69) and LTA vs. MEA (r=0.56), with moderate agreement (κ=0.46 and κ=0.46), but between VN assay and MEA, both devices using whole blood showed a lower correlation (r=0.42) and agreement (κ=0.3). Our results provide guidance regarding cut-off levels for LTA, VerifyNow and MEA assays to detect the CYP2C19 LOF allele in patients during dual antiplatelet maintenance therapy.
authors: Department of Cardiology, Dong-A University Hospital , Busan , South Korea .
authors: Hong-Zhe
authors: HZ
authors: Zhang
authors: Moo Hyun
authors: MH
authors: Kim
authors: Jin-Yeong
authors: JY
authors: Han
authors: Young-Hoon
authors: YH
authors: Jeong
mesh_terms: D000483:Alleles; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics / Q000378:metabolism*; D054855:Drug-Eluting Stents / Q000009:adverse effects; D005838:Genotype; D006801:Humans; D017202:Myocardial Ischemia / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects; D010641:Phenotype; D015539:Platelet Activation / Q000187:drug effects / Q000235:genetics; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D010979:Platelet Function Tests; D012372:ROC Curve; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine; D001241:Aspirin