Efficacy of Clopidogrel-Aspirin Therapy for Stroke Does Not Exist in
C
YP2C19 Loss-of-Function Allele Noncarriers With Overweight/Obesity
Authors: Mo Jinglin , Chen Zimo , Xu Jie , Wang Anxin , Dai Liye , Cheng Aichun , Meng Xia , Li Hao , Wang Yongjun ,   on behalf of the CHANCE Investigators, Johnston S. Claiborne , Wang Yilong , Zhao Xingquan , Wang Zhimin , Xia Haiqin , Li Bin , Zhang Guiru , Ren Xudong , Ji Chunling , Zhang Guohua , Li Jianhua , Lu Bohua , Wang Liping , Feng Shutao , Wang Dali , Tang Weiguo , Li Juntao , Zhang Hongtian , Li Guanglai , Wang Baojun , Chen Yuhua , Lian Ying , Liu Bin , Teng Junfang , Sui Rubo , Li Lejun , Yuan Zhiling , Zang Dawei , Lu Zuneng , Sun Li , Wang Dong , Hou Liying , Yuan Dongcai , Cao Yongliang , Li Hui , Tan Xiuge , Wang Huicong , Du Haisong , Liu Mingyi , Wang Suping , Liu Qiuwu , Zhang Zhong , Cui Qifu , Wang Runqing , Zhao Jialin , Zhang Jiewen , Zhao Jianping , Bi Qi , Qi Xiyou , Liu Junyan , Li Changxin , Li Ling , Pan Xiaoping , Zhang Junling , Jiao Derang , Han Zhao , Qian Dawei , Xiao Jin , Xing Yan , Du Huishan , Huang Guang , Cui Yongqiang , Li Yan , Feng Lianyuan , Gao Lianbo , Xiao Bo , Cao Yibin , Wu Yiping , Liu Jinfeng , Zhang Zhiming , Dong Zhengxie , Wang Limin , He Li , Wang Xinchen , Guo Xueying , Wang Ming , Wang Xiaosha , Jiang Jiandong , Zhao Renliang , Zhou Shengnian , Hu Hao , He Maolin , Yu Fengchun , Ouyang Quping , Zhang Jingbo , Xu Anding , Qi Xiaokun , Wang Lei , Shi Fuming , Guo Fuqiang , Wang Jianfeng , Zhao Fengli , Dou Ronghua , Wei Dongning , Meng Qingwei , Xia Yilu , Wang Shimin , Xue Zhangcang , Xu Yuming , Ma Liping , Wang Chun , Wu Jiang , Du Yifeng , Wang Yinzhou , Xiao Lijun , Song Fucong , Hu Wenli , Chen Zhigang , Liu Qingrui , Zhang Jiemin , Chen Mei , Yuan Xiaodong , Liu Zhihui , Li Guozhong , Li Xiaohong , Tian Tingchen 
Published: November 2019

Background and Purpose—

The role of dual-antiplatelet therapy with clopidogrel plus aspirin has been demonstrated to substantially decrease the risk of recurrent stroke among patients with minor stroke and transient ischemic attack. We aimed to determine whether the efficacy of clopidogrel-aspirin therapy among patients with minor stroke / transient ischemic attack was influenced by the stratification of
CYP2C19
genotype and body mass index (BMI).

Methods—

CYP2C19
loss-of-function allele (LoFA) carriers were defined as patients with either LoFA of *2 or *3. Low/normal weight and overweight/obesity was defined as BMI <25 and ≥25 kg/m
2
, respectively. Primary outcome was defined as stroke recurrence at 3 months.

Results—

In a total of 2933 patients, there were 1726 (58.8%) LoFA carriers and 1275 (43.5%) patients with overweight/obesity (BMI ≥25 kg/m
2
). Stratified analyses by LoFA carrying status and BMI, hazard ratios (hazard ratios 95% CIs) of the clopidogrel-aspirin therapy for stroke recurrence were 0.90 (0.60–1.36), 0.87 (0.56–1.35), 0.65 (0.39–1.09), and 0.40 (0.22–0.71) among subgroups of LoFA carriers with overweight/obesity, LoFA carriers with low/normal weight, LoFA noncarriers with overweight/obesity, and LoFA noncarriers with low/normal weight, respectively, with
P
=0.049 for interaction.

Conclusions—

Efficacy of clopidogrel-aspirin therapy in reducing the risk of stroke recurrence is not present in
CYP2C19
LoFA noncarriers with overweight/obesity. Our study suggests that BMI significantly influences the correlation between
CYP2C19
genotype and efficacy of clopidogrel-aspirin therapy.

Clinical Trial Registration—

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT00979589.