title: Evaluation of the incremental prognostic value of the combination of CYP2C19 poor metabolizer status and ABCB1 3435 TT polymorphism over conventional risk factors for cardiovascular events after drug-eluting stent implantation in East Asians.
abstract: We evaluated the incremental prognostic value of combining the CYP2C19 poor metabolizer (PM) and ABCB1 3435 TT for adverse clinical outcomes over conventional risk factors in a percutaneous coronary intervention (PCI) cohort.
  
  
  
  We enrolled 2,188 patients. The primary end point was a composite of death from any cause, nonfatal myocardial infarction (MI), and stroke during 1-year follow-up. The population was stratified into the following four groups: CYP2C19 EM/IM+ABCB1 3435 CC/CT, CYP2C19 EM/IM+ABCB1 3435 TT, CYP2C19 PM+ABCB1 3435 CC/CT, and CYP2C19 PM+ABCB1 3435 TT.
  
  
  
  A total of 87 (3.97%) primary end-point events occurred (64 deaths, 8 non-fatal MIs and 15 strokes). Multivariate Cox analysis indicated that CYP2C19 PM+ABCB1 3435 TT status was a significant predictor of the primary end point (hazard ratio = 4.51, 95% confidence interval (CI) = 1.92-10.58). However, addition of combined genetic status to the clinical risk model did not improve the model discrimination (C-statistic = 0.786 (95% CI = 0.734-0.837) to 0.785 (95% CI = 0.733-0.838)) or risk reclassification (categorical net reclassification improvement (0.040, P = 0.32), integrated discrimination improvement (0.021, P = 0.026)).
  
  
  
  In a real-world East Asian PCI population taking clopidogrel, although the concurrent presence of CYP2C19 PM and ABCB1 TT is a strong independent predictor of adverse outcomes, the combined status of two at-risk variants does not have an incremental prognostic value beyond that of the conventional clinical risk factors.Genet Med 18 8, 833-841.
authors.affiliation: Department of Cardiology, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Mahn-Won
authors.identifier: 0000-0001-5293-8461
authors.initials: MW
authors.lastname: Park
authors.affiliation: Department of Cardiology, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Her
authors.affiliation: Department of Cardiology, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Chan Joon
authors.initials: CJ
authors.lastname: Kim
authors.affiliation: Department of Cardiology, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Jung
authors.initials: J
authors.lastname: SunCho
authors.affiliation: Department of Cardiology, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Gyung-Min
authors.initials: GM
authors.lastname: Park
authors.affiliation: Department of Cardiology, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Tae-Seok
authors.initials: TS
authors.lastname: Kim
authors.affiliation: Department of Cardiology, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Yun-Seok
authors.initials: YS
authors.lastname: Choi
authors.affiliation: Department of Cardiology, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Chul-Soo
authors.initials: CS
authors.lastname: Park
authors.affiliation: Department of Cardiology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Yoon-Seok
authors.initials: YS
authors.lastname: Koh
authors.affiliation: Department of Cardiology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Hun-Jun
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Department of Cardiology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Pum-Joon
authors.initials: PJ
authors.lastname: Kim
authors.affiliation: Department of Cardiology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Wook-Sung
authors.initials: WS
authors.lastname: Chung
authors.affiliation: Department of Cardiology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Ki-Bae
authors.initials: KB
authors.lastname: Seung
authors.affiliation: Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Gimhae, Korea.|Department of Clinical Pharmacology, Inje University Busan Paik Hospital, Gimhae, Korea.
authors.forename: Ho-Sook
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Gimhae, Korea.|Department of Clinical Pharmacology, Inje University Busan Paik Hospital, Gimhae, Korea.
authors.forename: Jae-Gook
authors.initials: JG
authors.lastname: Shin
authors.affiliation: Department of Cardiology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Kiyuk
authors.initials: K
authors.lastname: Chang
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D001241:Aspirin / Q000008:administration & dosage / Q000493:pharmacokinetics; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D054855:Drug-Eluting Stents; D005202:Asia, Eastern; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects*; D000071184:Pharmacogenomic Variants; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011379:Prognosis; D012307:Risk Factors; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine; D001241:Aspirin