1. 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.
- Author
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Park MW, Her SH, Kim CJ, SunCho J, Park GM, Kim TS, Choi YS, Park CS, Koh YS, Park HJ, Kim PJ, Chung WS, Seung KB, Kim HS, Shin JG, and Chang K
- Subjects
- ATP Binding Cassette Transporter, Subfamily B genetics, Aged, Aged, 80 and over, Aspirin administration & dosage, Aspirin pharmacokinetics, Clopidogrel, Drug-Eluting Stents, Asia, Eastern, Female, Humans, Male, Middle Aged, Pharmacogenomic Variants, Platelet Aggregation Inhibitors pharmacokinetics, Prognosis, Risk Factors, Ticlopidine administration & dosage, Ticlopidine analogs & derivatives, Ticlopidine pharmacokinetics, Asian People genetics, Cytochrome P-450 CYP2C19 genetics, Mutation, Percutaneous Coronary Intervention adverse effects, Platelet Aggregation Inhibitors administration & dosage
- Abstract
Purpose: 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., Methods: 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., Results: 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))., Conclusions: 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.
- Published
- 2016
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