Han Sang Won, Kim Yong-Jae, Ahn Seong Hwan, Seo Woo-Keun, Yu Sungwook, Oh Seung-Hun, Nam Hyo Suk, Choi Hye-Yeon, Yoon Sung Sang, Kim Seo Hyun, Lee Jong Yun, Lee Jun Hong, Hwang Yang-Ha, Lee Kee Ook, Jung Yo Han, Lee Jun, Sohn Sung-Il, Kim Youn Nam, Lee Kyung-A, Bushnell Cheryl D, Lee Kyung-Yul
Department of Neurology, Inje University College of Medicine, Seoul, Korea.
Department of Neurology, Ewha Womans University School of Medicine, Seoul, Korea.
J Stroke. 2017 Sep;19(3):356-364. doi: 10.5853/jos.2017.01249. Epub 2017 Sep 29.
To compare the efficacy and safety of antiplatelet agents for the secondary prevention of ischemic stroke based on cytochrome P450 2C19 (CYP2C19) polymorphisms.
This study was a prospective, multicenter, randomized, parallel-group, open-label, blind genotype trial. First time non-cardiogenic ischemic stroke patients were enrolled and screened within 30 days. Participants were randomized to receive either triflusal or clopidogrel for secondary stroke prevention. The primary outcome was the time from randomization to first recurrent ischemic stroke or hemorrhagic stroke.
The required sample size was 1,080 but only 784 (73%) participants were recruited. In patients with a poor CYP2C19 genotype for clopidogrel metabolism (n=484), the risk of recurrent stroke among those who received triflusal treatment was 2.9% per year, which was not significantly different from those who received clopidogrel treatment (2.2% per year; hazard ratio [HR], 1.23; 95% confidence interval [CI], 0.60-2.53). In the clopidogrel treatment group (n=393), 38% had good genotypes and 62% poor genotypes for clopidogrel metabolism. The risk of recurrent stroke in patients with a good CYP2C19 genotype was 1.6% per year, which was not significantly different from those with a poor genotype (2.2% per year; HR, 0.69; 95% CI, 0.26-1.79).
Whilst there were no significant differences between the treatment groups in the rates of stroke recurrence, major vascular events, or coronary revascularization, the efficacy of antiplatelet agents for the secondary prevention of stroke according to CYP2C19 genotype status remains unclear.
基于细胞色素P450 2C19（CYP2C19）基因多态性比较抗血小板药物在缺血性卒中二级预防中的疗效与安全性。
本研究为前瞻性、多中心、随机、平行组、开放标签、盲法基因型试验。首次非心源性缺血性卒中患者在30天内入组并接受筛查。参与者被随机分配接受曲氟尿苷或氯吡格雷进行卒中二级预防。主要结局是从随机分组到首次复发性缺血性卒中或出血性卒中的时间。
所需样本量为1080例，但仅招募到784例（73%）参与者。在氯吡格雷代谢CYP2C19基因型不佳的患者（n = 484）中，接受曲氟尿苷治疗者每年复发性卒中风险为2.9%，与接受氯吡格雷治疗者（每年2.2%；风险比[HR]，1.23；95%置信区间[CI]，0.60 - 2.53）无显著差异。在氯吡格雷治疗组（n = 393）中，38%氯吡格雷代谢基因型良好，62%不佳。CYP2C19基因型良好的患者每年复发性卒中风险为1.6%，与基因型不佳者（每年2.2%；HR，0.69；95% CI，0.26 - 1.79）无显著差异。
虽然各治疗组在卒中复发率、主要血管事件或冠状动脉血运重建率方面无显著差异，但根据CYP2C19基因型状态，抗血小板药物在卒中二级预防中的疗效仍不明确。
