AIMS: despite treatment with clopidogrel on top of aspirin, stent thrombosis (ST) still occurs being the most serious complication after percutaneous coronary interventions (PCIs). In this study, we aimed to determine the effect of variations in genes involved in the absorption (ABCB1 C1236T, G2677T/A, C3435T), metabolism (CYP2C19*2 and *3, CYP2C9*2 and *3, CYP3A4*1B and CYP3A5*3), and pharmacodynamics (P2Y1 A1622G) of clopidogrel on the occurrence of ST. METHODS AND RESULTS: the selected genetic variants were assessed in 176 subjects who developed ST while on dual antiplatelet therapy with aspirin and clopidogrel and in 420 control subjects who did not develop adverse cardiovascular events, including ST, within 1 year after stenting. The timing of the definite ST was acute in 66, subacute in 87, and late in 23 cases. The presence of the CYP2C19*2 and CYP2C9*3 variant alleles was significantly associated with ST (OR(adj): 1.7, 95% CI: 1.0-2.6, P = 0.018 and OR(adj): 2.4, 95% CI: 1.0-5.5, P = 0.043, respectively). The influence of CYP2C19*2 (OR(adj): 2.5, 95% CI: 1.1-5.5, P = 0.026) and CYP2C9*3 (OR(adj): 3.3, 95% CI: 1.1-9.9, P = 0.031) was most strongly associated with subacute ST. No significant associations of the other genetic variations and the occurrence of ST were found. CONCLUSION: carriage of the loss-of-function alleles CYP2C19*2 and CYP2C9*3 increases the risk on ST after PCI.
AIMS: despite treatment with clopidogrel on top of aspirin, stent thrombosis (ST) still occurs being the most serious complication after percutaneous coronary interventions (PCIs). In this study, we aimed to determine the effect of variations in genes involved in the absorption (ABCB1C1236T, G2677T/A, C3435T), metabolism (CYP2C19*2 and *3, CYP2C9*2 and *3, CYP3A4*1B and CYP3A5*3), and pharmacodynamics (P2Y1 A1622G) of clopidogrel on the occurrence of ST. METHODS AND RESULTS: the selected genetic variants were assessed in 176 subjects who developed ST while on dual antiplatelet therapy with aspirin and clopidogrel and in 420 control subjects who did not develop adverse cardiovascular events, including ST, within 1 year after stenting. The timing of the definite ST was acute in 66, subacute in 87, and late in 23 cases. The presence of the CYP2C19*2 and CYP2C9*3 variant alleles was significantly associated with ST (OR(adj): 1.7, 95% CI: 1.0-2.6, P = 0.018 and OR(adj): 2.4, 95% CI: 1.0-5.5, P = 0.043, respectively). The influence of CYP2C19*2 (OR(adj): 2.5, 95% CI: 1.1-5.5, P = 0.026) and CYP2C9*3 (OR(adj): 3.3, 95% CI: 1.1-9.9, P = 0.031) was most strongly associated with subacute ST. No significant associations of the other genetic variations and the occurrence of ST were found. CONCLUSION: carriage of the loss-of-function alleles CYP2C19*2 and CYP2C9*3 increases the risk on ST after PCI.
Authors: Thomas O Bergmeijer; Jean-Luc Reny; Ruth E Pakyz; Li Gong; Joshua P Lewis; Eun-Young Kim; Daniel Aradi; Israel Fernandez-Cadenas; Richard B Horenstein; Ming Ta Michael Lee; Ryan M Whaley; Joan Montaner; Gian Franco Gensini; John H Cleator; Kiyuk Chang; Lene Holmvang; Willibald Hochholzer; Dan M Roden; Stefan Winter; Russ B Altman; Dimitrios Alexopoulos; Ho-Sook Kim; Jean-Pierre Déry; Meinrad Gawaz; Kevin Bliden; Marco Valgimigli; Rossella Marcucci; Gianluca Campo; Elke Schaeffeler; Nadia P Dridi; Ming-Shien Wen; Jae Gook Shin; Tabassome Simon; Pierre Fontana; Betti Giusti; Tobias Geisler; Michiaki Kubo; Dietmar Trenk; Jolanta M Siller-Matula; Jurriën M Ten Berg; Paul A Gurbel; Jean-Sebastien Hulot; Braxton D Mitchell; Matthias Schwab; Marylyn DeRiggi Ritchie; Teri E Klein; Alan R Shuldiner Journal: Am Heart J Date: 2017-12-17 Impact factor: 4.749
Authors: Thomas O Bergmeijer; Gerrit Ja Vos; Daniël Mf Claassens; Paul Wa Janssen; Remko Harms; Richard van der Heide; Folkert W Asselbergs; Jurriën M Ten Berg; Vera Hm Deneer Journal: Pharmacogenomics Date: 2018-04-27 Impact factor: 2.533
Authors: M Lin; M Todaro; J Chan; L Churilov; W S Zhu; S Ramdave; P J Mitchell; R J Dowling; P Kwan; B Yan Journal: AJNR Am J Neuroradiol Date: 2015-09-03 Impact factor: 3.825