CYP2C192 and CYP2C93 alleles are associated with stent thrombosis: a case–control study

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/...

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Published in:European heart journal 2010-12, Vol.31 (24), p.3046-3053
Main Authors: Harmsze, Ankie M., van Werkum, Jochem W., ten Berg, Jurriën M., Zwart, Bastiaan, Bouman, Heleen J., Breet, Nicoline J., van 't Hof, Arnoud W.J., Ruven, Hendrik J.T., Hackeng, Christian M., Klungel, Olaf H., de Boer, Anthonius, Deneer, Vera H.M.
Format: Article
Language:English
Subjects:
Absorption
Aged
Angioplasty, Balloon, Coronary - methods
Aryl Hydrocarbon Hydroxylases - genetics
Aspirin - therapeutic use
Blood Vessel Prosthesis
Case-Control Studies
Clopidogrel
Cytochrome P-450 CYP2C19
Cytochrome P-450 CYP2C9
Drug Therapy, Combination
Female
Genetic variants
Genotype
Graft Occlusion, Vascular - genetics
Heterozygote
Humans
Male
Metabolism
Middle Aged
Percutaneous coronary intervention
Platelet Aggregation Inhibitors - therapeutic use
Stent thrombosis
Stents
Ticlopidine - analogs & derivatives
Ticlopidine - therapeutic use
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Summary: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 (ORadj: 1.7, 95% CI: 1.0–2.6, P = 0.018 and ORadj: 2.4, 95% CI: 1.0–5.5, P = 0.043, respectively). The influence of CYP2C19*2 (ORadj: 2.5, 95% CI: 1.1–5.5, P = 0.026) and CYP2C9*3 (ORadj: 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.
ISSN:0195-668X
1522-9645
DOI:10.1093/eurheartj/ehq321