Dual Antiplatelet Therapies and Causes in Minor Stroke or Transient Ischemic Attack: A Prespecified Analysis in the CHANCE-2 Trial
Authors: Xie Xuewei , Jing Jing , Meng Xia , Claiborne Johnston S. , Bath Philip M. , Li Zixiao , Zhao Xingquan , Liu Liping , Wang Yilong , Xu Qin , Wang Anxin , Jiang Yong , Li Hao , Wang Yongjun , Wang Yongjun , Johnston S. Claiborne , Xu Anding , Bath Philip M. W. , Dong Qiang , Wang Yongjun , Li Hao , Meng Xia , Jing Jing , Xie Xuewei , Lin Jinxi , Simon Tabassome , Danchin Nicolas , Zhi Helen , Peng Bin , Fan Dongsheng , Wang David , Youn Teddy , Adams Harold P. , Meng Xia , Xie Xuewei , Jing Jing , Lin Jinxi , Niu Siying , Li Hao , Pan Yuesong , Wang Anxin , Jiang Yong , Jin Aoming , Wu Haibo , Shi Wei , Wu Haibo , Li Jianhua , Wang Yanxia , Wei Yan , Liu Haichao , Zhao Jianhua , Han Xinshen , Sheng Baoying , Yang Xiaofan , Jing Ping , Chen Jiechun , Huang Panbing , Chen Guofang , Feng Yefang , Wu Lie , Zhu Runxiu , Liu Peiru , Chang Liguo , Yang Xiafeng , Wang Xinqiang , Zhao Jinguo , Zhang Wei , Cui Zhigang , Wu Xuemei , Huang Hua , Liu Qiuwu , Zhao Xingquan , Cheng Dongli , Zhu Yulan , Wang Lihua , Li Guozhong , Zhang Xiaoxuan , Xue Wenjun , Chen Guohua , Li Haipeng , Deng Ke , Liu Jingyao , Liu Yansong , Wei Xiu’e , Wang Dunjing , Feng Juan , Wang Baojun , Chen Yongming , Wu Bing , Chai Xiangting , Shi Fudong , Cai Xueli , Yang Hongqin , Zhang Yundong , Wang Xia , Wang Yumei , Shi Zhimin , Chen Shengli , Chen Yangmei , Zhou Lichun , Hong Weimin , Yin Lufeng , Ren Lijie , Ma Jianhua , Lei Yongqian , Wu Minghua , Zeng Guoyong , Wu Lingfeng , Cao Mingha , Guo Cunju , Man Honghao , Bai Yu , Wu Aimei , Huang Xuerong , Zhang Chunhua , Jiang Xiaoling , Shao Peining , Luo Dexin , Cai Zhiyou , Jia Yi , Ma Aijun , Bai Ying , Gong Xuhai , Liu Jirong , Zhang Meng , Xu Anding , Tan Hong , An Yi , Wang Zhimin , Zhao Weili , Wu Xiangbin , Gao Wenwei , Gao Yueqiang , Li Xinyi , Wu Jin , Wang Feng , Du Ganqin , Wu Kaiyi , Wan Hebin , Chu Lan , Hong Daojun , Cao Hui , Xu Bing , Liu Jie , Zhang Hao , Yang Jie , Zhang Guiru , Chen Hong , Zhang Jianling , Li Xuemei , Zou Yu’an , Wang Yan , Wei Xia , Wang Jianlin , Chen Weifeng , Liu Chunfeng , Sui Changbai , Li Hongyan , Zhong Hua , Wu Aisheng , Fan Jinqi , Ji Qiuhong , Lin Jinshen , Shi Xueying , Kang Guangming , Xie Haiyang , Ma Dan , Wang Hongliang , Chen Wei , Shi Peng , Shangguan Wen , Gu Jun , Feng Xiaopeng , Zhan Qunling , Han Xianwen , Cao Hongyuan , Wei Liang , Lu Weifeng , Zheng Chunling , Yang Chunjie , Zhao Min , Wu Heng , Dong Chunhua , He Yongli , Yao Shufang , Zhu Xiangyang , Zhao Zhong , Ye Min , Cai Guodong , Peng Guangyao , Li Hongfei , Zhang Lujun , Zhang Shoucheng , Zhou Wei , Liu Hong , Fan Xuewen , Tan Wei , Zhu Renxiang , He Tianhui , Wang Qizhang , Zhang Lifang , Yang Jinsuo , Liu Yuqing , Su Shaohua , He Li , Yu Yadong , Wei Zhang , Zhankui Lin , Rong Qiu Xue , Bin Qi Ying , Sheng Lei , Zheng Wu Shi , Di Wu Song , Liang Wu Sheng , Qin Ding , Xiao Bo , Wang Kai , Ting Zhang Xi , Jing Pang Jin 
Published: August 2023

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.