Niu Xuan, Mao Ling, Huang Yan, Baral Suraj, Li Jian-Yong, Gao Yuan, Xia Yuan-Peng, He Quan-Wei, Wang Meng-Die, Li Man, Zou Li, Miao Xiao-Ping, Hu Bo
Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
J Huazhong Univ Sci Technolog Med Sci. 2015 Apr;35(2):147-156. doi: 10.1007/s11596-015-1404-7. Epub 2015 Apr 16.
Several studies have investigated the association between CYP2C19 polymorphism and clinical outcomes of patients treated with clopidogrel, but few have noticed the difference in association between Westerners and Asians. We searched MEDLINE, EMBASE and Cochrane Library database and conducted a systematic review and meta-analysis. Thirty-six studies involving 44 655 patients with coronary artery disease (CAD) treated with clopidogrel were included, of which more than 68% had undergone percutaneous coronary intervention (PCI). The primary outcome of our interest was the recurrence of major adverse cardiovascular events (MACE) in those CAD patients. Firstly, we found that the distribution of reduced-function CYP2C19 allele varied between Westerners and Asians. Among Asians, 1 and 2 reduced-function CYP2C19 mutant allele carriers accounted for 42.5% and 10%, respectively. While among Westerners, 1 and 2 reduced-function CYP2C19 mutant allele carriers accounted for 25.5% and 2.4%, respectively. Secondly, the impact of CYP2C19 polymorphism on clinical outcomes of patients treated with clopidogrel varied with races. Among Asians, only 2 reduced-function CYP2C19 mutant allele carriers had the reduced effect of clopidogrel. And the reduced effect was significant only after the 30th day of treatment. While among Westerners, both 1 and 2 reduced-function CYP2C19 allele carriers had the reduced effect, and it mainly occurred within the first 30 days. Thirdly, the safety of clopidogrel was almost the same among races. Reduced-function allele non-carriers had higher risk for total bleeding but did not have higher risk for major bleeding. It is suggested that CYP2C19 polymorphism affects the efficacy of clopidogrel differently among Westerners and Asians.
多项研究调查了CYP2C19基因多态性与接受氯吡格雷治疗患者临床结局之间的关联,但很少有人注意到西方人与亚洲人在这种关联上的差异。我们检索了MEDLINE、EMBASE和Cochrane图书馆数据库,并进行了系统评价和荟萃分析。纳入了36项研究,共44655例接受氯吡格雷治疗的冠心病(CAD)患者,其中超过68%接受了经皮冠状动脉介入治疗(PCI)。我们感兴趣的主要结局是这些CAD患者主要不良心血管事件(MACE)的复发情况。首先,我们发现功能降低的CYP2C19等位基因分布在西方人和亚洲人之间存在差异。在亚洲人中,携带1个和2个功能降低的CYP2C19突变等位基因的携带者分别占42.5%和10%。而在西方人中,携带1个和2个功能降低的CYP2C19突变等位基因的携带者分别占25.5%和2.4%。其次,CYP2C19基因多态性对接受氯吡格雷治疗患者临床结局的影响因种族而异。在亚洲人中,只有携带2个功能降低的CYP2C19突变等位基因的携带者氯吡格雷疗效降低。且这种降低的效果仅在治疗第30天后才显著。而在西方人中,携带1个和2个功能降低的CYP2C19等位基因的携带者均有疗效降低的情况,且主要发生在治疗的前30天内。第三,氯吡格雷在不同种族中的安全性几乎相同。非携带功能降低等位基因者发生总出血的风险较高,但发生大出血的风险并不高。提示CYP2C19基因多态性对氯吡格雷疗效在西方人和亚洲人中的影响不同。