Immediate- or Delayed-Intensive Statin in Acute Cerebral Ischemia
Authors: Gao Ying , Jiang Lingling , Pan Yuesong , Chen Weiqi , Jing Jing , Wang Chunjuan , Johnston S. Claiborne , Amarenco Pierre , Bath Philip M. , Yang Yingying , Wang Tingting , Han Shangrong , Meng Xia , Lin Jinxi , Zhao Xingquan , Liu Liping , Zhao Jinguo , Li Ying , Zang Yingzhuo , Zhang Shuo , Yang Hongqin , Yang Jianbo , Wang Yuanwei , Li Dali , Wang Yanxia , Liu Dongqi , Kang Guangming , Wang Yongjun , Wang Yilong ,   INSPIRES Investigators, Wang Zhimin , Guo Jianmin , Song Xiujuan , Wang Xinqiang , Lu Weifeng , Huang Panbing , Li Feng , Wang Lihua , Xiao Weigang , Cao Yibin , Rong Liangqun , Xing Ying , Ma Lili , Zhou Yanhua , Han YuQing , Fang Jingxian , Liu Jie , Shangguan Wen , Liu Bin , Li Jianhua , Han Yan , Song Chengguang , Song Xuhong , Lv Yuanfeng , Xu Changqing , Ma Congmin , Duan Zhihui , Pan Yungao , Ren Lijie , Li Bin , Fan Jinqi , Zhang Yuanren , Li Jingfang , Wang Baojun , Gu Jun , Yin Xiaoping , Wang Xiao , Chang Liguo , Gong Kaoling , Zhang Wenhua , Che Yu , Wan Yinyuan , Gui Linying , Sun Ping , Jia Zhonghai , Liu Haichao , Meng Qinglian , Chai Donghe , Zhang Lei , Li Guofeng , Jin Huafeng , Liu Gexia , Tang Yonghong , Mei Xiaomin , Zou Guoping , Yang Yuefeng , Li Quanhao , Tian Xiju , Chen Hong , Xiao Jialiang , Song Xiaoming , Li Guangning , Li Guozhong , Yang Chunjie , Zhang Xiting , Wang Chun , Hu Jizheng , Hu Wei , Jiao Zhen , Lu Yunnan , Xia Zhangyong , Wang Yufen , Wang Yinshan , Qi Jinxing , Wang Xiaoping , Liu Shuqin , Li Bo , Li Yinghui , Sun Yaming , Jing Ping , Wu Jialing , Yang Bo , Zhang Jinghua , Zhang Tianxia , Zheng Chunling , Li Lejun , Li Huimin , Yu Fumin , Yao Shufang , Chang Jianjun , Li Dongqun , Du Ganqin , Zhao Yi , Liang Pengfei , Wang Ming , Fang Qi , Deng Youqing , Gao Xuzhao , Zhu Runxiu , Xie Yimin , Liu Yanshu , Yuan Yi , Wu Qiuyi , Zhao Guimei , Yang Yan , Lu Yong , Zhao Weidong , Chen Tianbao , Pan Deng , Yang Min , Xue Baoguo , Zhang Ge , Zhao Yanjiang , Wei Yunfei , Yun Wenwei , Chen Xiaoqi , Wu Danhong , Zhang Lifang , Sheng Baoying , Cui Zhigang , Xie Xiangdong , Cheng Guanghui , Zhang Yifei , Zhu Ruiming , Chen Yong , Liu GuoHua , Feng Lei , Long Zhihua , Chen Huisheng , Zhang Ping , Cui Yuanliang , Zhang Yongli , Han Yazhou , Bai Yajie , Tang Tieyu , Wu Songdi , Gong Wenping , Wang Jun , Zhu Zhishan , Ma Xiaoyan , Yao Leyi , Li Runhui , Zhu Shuanggen , Li Juntao , Qi Xiuhui , Jiang Zhongping , Liang Zhigang , Liu Chunping , Xu Dongjuan , Qiu Tao , Chen Chunping , Tan Hong , Chen Shengli , Yang Chunshui , Jun Wei , He Qing , Sun Zengqiang , Li Shen , Guo Cunju , Wang Hongliang , Li Dongfang , Wu Hongbin , Zhen Wenxu , Wang Lijun , Hong Wenke , Qiu Xuerong , Wei Xinxia , Lv Yongtao , Feng Xiangyang , Yang Gaiqing , Lin Songjun , Cao Aihua , Sun Dejin , Fu Pengcheng , Cao Cao , Xue Wenjun , Liu Haiyan , Li Shanshan , Qu Fang , Zhou Zhengguo , Liu Ping , Wang Lixia , Wu Yiping , Liu Jinxing , Sun Xin , Wang Qingyong , Li Xiaomei , Wang Qizhang , Wu Yongxiong , Liu Chunfeng , Zhao Yanxin , Lin Zhijian , Ma Rui , Li Jiedan , Zhu Zhishun , Guo Lili , Sun Bing , Tan Jun , Yang Ke , Bi Yong , Duan Yingjie , Li Shaochun , Lou Xiaoliang , Huang Xiaosong , Zang Fucai , Dong Yonghua , Zhao Jingyan , Cui Yanzeng , Zhang Zili , Zhang Yali , Yan Peng , Fan Huixian , Ji Qiuhong , Wu Aisheng , Han Xinshen , Liu Li , Song Jie , Liu Shuting , Che Xiaoyu , Liang Xianhong , Li Shangzhi , Qi Nan , Chen Xiaolei , Liu Chenhui , Pi Jingtao , Tian Yu , Wang Nan , Li Zhengyang , Luo Biyang , Yue Fanfang , Guo Lei , Hu Kun , Zhong Xi , Lu Jiawei , Wang Long , Yu Jiandong , Zhang Xiaowu , Zhou Mengyuan , Chen Yiyi , Ji Zhiyuan , Li Jianying , Yan Hongyi , Wang Mengxing , Wu Haibo 
Published: May 2024

Importance

Comparisons are limited for immediate-intensive and delayed-intensive statin for secondary stroke prevention and neuroprotection in patients with acute mild ischemic stroke or transient ischemic attack (TIA) from atherosclerosis.

Objective

To estimate whether immediate-intensive statin therapy is safe and can lower the risk of recurrent stroke compared with delayed-intensive statin in patients with acute mild ischemic stroke or high-risk TIA from atherosclerosis.

Design, Setting, and Participants

The Intensive Statin and Antiplatelet Therapy for High-Risk Intracranial or Extracranial Atherosclerosis (INSPIRES) trial, a double-blind, placebo-controlled, 2 × 2 factorial, randomized clinical trial enrolled patients from September 2018 to October 2022. The trial was conducted at 222 hospitals in China. Patients aged 35 to 80 years with mild ischemic stroke or high-risk TIA of presumed atherosclerosis within 72 hours of symptom onset were assessed.

Interventions

Patients were randomly assigned to receive immediate-intensive atorvastatin (80 mg daily on days 1-21; 40 mg daily on days 22-90) or 3-day delayed treatment (placebo for days 1-3, followed by placebo and atorvastatin, 40 mg daily on days 4-21, and then atorvastatin, 40 mg daily on days 22-90).

Main Outcomes and Measures

The primary efficacy outcome was new stroke within 90 days, and a secondary efficacy outcome was poor functional outcome. Moderate to severe bleeding was the primary safety outcome.

Results

A total of 11 431 patients were assessed for eligibility, and 6100 patients (median [IQR] age, 65 [57-71] years; 3915 men [64.2%]) were enrolled, with 3050 assigned to each treatment group. Within 90 days, new stroke occurred in 245 patients (8.1%) in the immediate-intensive statin group and 256 patients (8.4%) in the delayed group (hazard ratio, 0.95; 95% CI, 0.80-1.13). Poor functional outcome occurred in 299 patients (9.8%) and 348 patients (11.4%) in the immediate-intensive and delayed-intensive statin groups, respectively (odds ratio, 0.83; 95% CI, 0.71-0.98). Moderate to severe bleeding occurred in 23 of 3050 patients (0.8%) and 17 of 3050 patients (0.6%), in the immediate-intensive and delayed-intensive statin groups, respectively.

Conclusions and Relevance

Immediate-intensive statin initiated within 72 hours did not reduce the risk of stroke within 90 days and may be associated with improved functional outcomes without significant difference in moderate to severe bleeding, compared with 3-day delayed-intensive statin in Chinese patients with acute mild ischemic stroke or TIA from atherosclerosis.

Trial Registration

ClinicalTrials.gov Identifier: NCT03635749