Gene variants in responsiveness to clopidogrel have no impact on clinical outcomes in Chinese patients undergoing percutaneous coronary intervention - A multicenter study
Gene variants in responsiveness to clopidogrel have no impact on clinical outcomes in Chinese patients undergoing percutaneous coronary intervention - A multicenter study
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对氯吡格雷反应性的基因变异对接受经皮冠状动脉介入治疗的中国患者的临床结果没有影响——一项多中心研究
DOI：
10.1016/j.ijcard.2017.03.015
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发表时间：
2017-08-01
影响因子：
3.5
通讯作者：
Wang, Dao Wen
中科院分区：
文献类型：
--
作者：
Li, Chenze;Zhang, Lina;Wang, Dao Wen
背景：基因变异有助于个体对氯吡格雷反应的变异性，并影响高加索急性冠脉综合征（ACS）患者的心血管结局。然而，亚洲人群的数据有限。方法：我们对138例ACS患者氯吡格雷代谢和活性途径中的14个基因进行了重新测序，并前瞻性评估了13个可能与氯吡格雷疗效相关的变异对5820例ACS患者经皮冠状动脉介入治疗（PCI）后一年心血管事件发生的调节作用。此外，对1084名参与者的血小板聚集率进行了测量，并对15名患者的血浆活性代谢物水平进行了测定，以测试增加氯吡格雷维持剂量是否会增加活性代谢物暴露。结果：与非携带者相比，CYP2C19*2携带者的治疗期血小板聚集率略高，活性代谢物暴露率略低（中位数[IQR] 51.49[35.43-66.75]比49.05 [32.36-63.38],P = 0.012）（平均值+/- SD AUC， 22.84 +/- 5.00比35.05 +/- 12.34,P = 0.008），但检测的任何变异与心血管事件风险之间均未发现显著相关性（P < 0.05）。在CYP2C19*2携带者中，从每日75 mg氯吡格雷切换到每日150 mg完全克服了氯吡格雷活性代谢物的低暴露（mean +/- SD AUC, 32.35 +/- 8.65 vs. 35.05 +/- 12.34, P = 0.314）。结论：与高加索人群不同，基因变异对中国ACS患者PCI术后血小板和氯吡格雷活性代谢物水平的抑制作用较轻，对血小板和氯吡格雷活性代谢物水平的影响较小，每日剂量增加至150mg可以克服这一影响。(C) 2017由爱思唯尔爱尔兰有限公司出版。
Background: Gene variants contribute to variability in individual responsiveness to clopidogrel and influence cardiovascular outcomes in Caucasian patients with acute coronary syndrome (ACS). However, limited data is available in Asian populations.Methods: We resequenced 14 genes in metabolizing and activity pathway of clopidogrel in 138 patients with ACS and prospectively assessed the modulating effects of 13 variants possibly related to clopidogrel efficacy on one-year cardiovascular event occurrence in 5820 ACS patients after percutaneous coronary intervention (PCI). In addition, platelet aggregation rate was measured in 1084 participants and plasma levels of active metabolite were determined in 15 patients to test whether increasing clopidogrel maintenance doses increases active metabolite exposure.Results: No significant associations were found between any of the tested variants and risk of cardiovascular events (P > 0.05), although CYP2C19*2 carriers had slightly higher on-treatment platelet aggregation rate and lower active metabolite exposure compared with that of non-carriers (Median [IQR] 51.49 [35.43-66.75] vs. 49.05 [32.36-63.38], P = 0.012) (means +/- SD AUC, 22.84 +/- 5.00 vs. 35.05 +/- 12.34, P = 0.008). Switching from 75 mg daily clopidogrel to 150 mg daily fully overcomes low exposure to clopidogrel active metabolite in CYP2C19*2 carriers (means +/- SD AUC, 32.35 +/- 8.65 vs. 35.05 +/- 12.34, P = 0.314).Conclusion: Different from Caucasian populations, genetic variants have no significant influence on clinical outcomes and have much milder effects on inhibition of platelet and active clopidogrel metabolite levels in Chinese patients with ACS after PCI, an effect which could be overcome with a dose escalation to 150 mg daily. (C) 2017 Published by Elsevier Ireland Ltd.