CYP2C19*2 and CYP2C9*3 alleles are associated with stent thrombosis: a case-control study

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. 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. Carriage of the loss-of-function alleles CYP2C19*2 and CYP2C9*3 increases the risk on ST after PCI.