Dual Antiplatelet Therapies and Causes in Minor Stroke or Transient Ischemic Attack: A Prespecified Analysis in the CHANCE-2 Trial
Xuewei Xie, Jing Jing, Xia Meng, S. Claiborne Johnston, Philip M. Bath, Zixiao Li, Xingquan Zhao, Liping Liu, Yilong Wang, Qin Xu, Anxin Wang, Yong Jiang, Hao Li, Yongjun Wang, Yongjun Wang, S. Claiborne Johnston, Anding Xu, Philip M. Bath, Qiang Dong, Yongjun Wang, Hao Li, Xia Meng, Jing Jing, Xuewei Xie, Jinxi Lin, Tabassome Simon, Nicolas Danchin, Helen Zhi, Bin Peng, Dongsheng Fan, David Wang, Teddy S. Youn, Harold P. Adams, Xia Meng, Xuewei Xie, Jing Jing, Jinxi Lin, Siying Niu, Hao Li, Yuesong Pan, Anxin Wang, Yong Jiang, Aoming Jin, Haibo Wu, Wei Shi, Haibo Wu, Jianhua Li, Yanxia Wang, Yan Wei, Haichao Liu, Jianhua Zhao, Xinshen Han, Bao-Ying Sheng, Xiaofan Yang, Jing Ping, Jie-Chun Chen, Panbing Huang, Guofang Chen, Yefang Feng, Lie Wu, Runxiu Zhu, Peiru Liu, Liguo Chang, Xiafeng Yang, Xinqiang Wang, Jinguo Zhao, Wei Zhang, Zhigang Cui, Xuemei Wu, Hua Huang, Qiuwu Liu, Xingquan Zhao, Dongli Cheng, Yulan Zhu, Lihua Wang, Guozhong Li, Xiao‐Xuan Zhang, Wenjun Xue, Guohua Chen, Haipeng Li, Ke Deng, Jing‐yao Liu, Yansong Liu, Xiue Wei, Dunjing Wang, Juan Feng, Baojun Wang, Yongming Chen, Bing Wu, Xiangting Chai, Fu‐Dong Shi, Xueli Cai, Hongqin Yang, Yundong Zhang, Xia Wang, Yumei Wang, Zhimin Shi, Shengli Chen, Yangmei Chen, Lichun Zhou
Abstract
BACKGROUND: It is unclear whether patients with different stroke/transient ischemic attack etiologies benefit differently from gene-directed dual antiplatelet therapy. This study explored the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin in transient ischemic attack or minor stroke with different causes in the CHANCE-2 trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events-II). METHODS: This was a prespecified analysis of the CHANCE-2 trial, which enrolled 6412 patients with minor stroke or transient ischemic attack who carried CYP2C19 loss-of-function alleles. Patients with centralized evaluation of TOAST (Trial of ORG 10172 in Acute Stroke Treatment) classification of large-artery atherosclerosis, small-vessel occlusion, and stroke of undetermined cause were included. The primary efficacy outcome was new stroke, and the primary safety outcome was severe or moderate bleeding, both within 90 days. Cox proportional hazards models were used to assess the interaction of TOAST classification with the effects of dual antiplatelet therapy with ticagrelor-aspirin versus clopidogrel-aspirin. RESULTS: A total of 6336 patients were included in this study. In patients administered ticagrelor-aspirin and clopidogrel-aspirin, respectively, stroke recurred in 85 (9.8%) and 88 (10.7%) patients with large-artery atherosclerosis (hazard ratio, 0.86 [95% CI, 0.63–1.18]; P =0.34); 32 (3.6%) and 61 (7.0%) patients with small-vessel occlusion (hazard ratio, 0.51 [95% CI, 0.33–0.79]; P =0.002); and 68 (4.8%) and 87 (5.9%) patients with stroke of undetermined cause (hazard ratio, 0.80 [95% CI, 0.58–1.10]; P =0.17), with P =0.08 for the treatment×cause subtype interaction effect. There were no significant differences in severe or moderate bleeding events in patients with different cause and different treatment. CONCLUSIONS: In this prespecified analysis of the CHANCE-2 trial, the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin in preventing new stroke were consistent in patients with different causes. The influence of stroke cause on benefit of gene-guided antiplatelet therapy should be explored by further trials. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04078737.