Influence of CYP2C19 loss-of-function variants on the antiplatelet effects and cardiovascular events in clopidogrel-treated Chinese patients undergoing percutaneous coronary intervention

Jian-Jun Zou, Hong-Guang Xie, Shao-Liang Chen, Jie Tan, Ling Lin, Ying-Ying Zhao, Hai-Mei Xu, Song Lin, Juan Zhang, Guang-Ji Wang
European Journal of Clinical Pharmacology 2013, 69 (4): 771-7

BACKGROUND AND OBJECTIVES: A large number of clinical studies have well demonstrated that the loss-of-function variant allele CYP2C19 2 is associated with attenuated response to clopidogrel and increased risk of developing stent thrombosis (ST) in white or black patients with stenting. However, similar association studies on the effect of the CYP2C19 2 and 3 variants on maximum platelet aggregation (MPA) and the risk of cardiovascular events are currently unavailable for the Chinese patients. This work was aimed at assessing the impact of the CYP2C19 2 and 3 variants on the antiplatelet effects and adverse cardiovascular events in clopidogrel-treated Chinese patients undergoing percutaneous coronary intervention (PCI).

METHODS: The study population consisted of 617 patients undergoing PCI. Genotypes were determined using MALDI/TOF-MS. MPA was measured by light transmittance aggregometry. The clinical end-point was the 1-year incidence of adverse cardiovascular events, including ST.

RESULTS: Carriers of CYP2C19 heterozygous (1/2, or 1/3; n = 278) and mutant homozygous (2/2, 2/3, or 3/3, n = 80) genotypes had significantly higher MPA values than noncarriers (1/1; n = 259; P = 0.036 and 0.007 respectively). Moreover, the presence of the CYP2C19 2 or 3 mutant allele was significantly associated with an increased risk of developing ST, with the higher risk of ST being seen in patients homozygous for the CYP2C19 2 or 3 variant allele than in noncarriers (OR, 13.58; 95% CI, 1.49-123.31; P = 0.012). Furthermore, multivariate analysis revealed an independent association of the presence of CYP2C19*2 and/or 3 variant alleles with greater MPA values (P = 0.001) and increased risk of ST (OR, 11.67; 95% CI, 1.21-78.83; P = 0.022). However, there was no significant influence of CYP2C19 2 and 3 on the risk of developing other adverse cardiovascular events.

CONCLUSIONS: Carriage of the loss-of-function genetic variants CYP2C19 2 and 3 is significantly associated with attenuated platelet response to clopidogrel and an increased risk of ST in Chinese patients treated with stenting.

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