• Ying Gao, Weiqi Chen, Yuesong Pan, Jing Jing, Chunjuan Wang, S Claiborne Johnston, Pierre Amarenco, Philip M Bath, Lingling Jiang, Yingying Yang, Tingting Wang, Shangrong Han, Xia Meng, Jinxi Lin, Xingquan Zhao, Liping Liu, Jinguo Zhao, Ying Li, Yingzhuo Zang, Shuo Zhang, Hongqin Yang, Jianbo Yang, Yuanwei Wang, Dali Li, Yanxia Wang, Dongqi Liu, Guangming Kang, Yongjun Wang, Yilong Wang, and INSPIRES Investigators.
• From the Department of Neurology, Beijing Tiantan Hospital (Y.G., W.C., Y.P., J.J., C.W., Y.Y., T.W., S.H., X.M., X.Z., L.L., Yongjun Wang, Yilong Wang), the Advanced Innovation Center for Human Brain Protection (Yongjun Wang, Yilong Wang), Beijing Laboratory of Oral Health (Yilong Wang), and Beijing Municipal Key Laboratory of Clinical Epidemiology (Yilong Wang), Capital Medical University, the China National Clinical Research Center for Neurological Diseases (Y.P., J.J., C.W., L.J., X.M., J.L., X.Z., L.L., Yongjun Wang, Yilong Wang), the National Center for Neurological Disorders (Yongjun Wang, Yilong Wang), the Research Unit of Artificial Intelligence in Cerebrovascular Disease, Chinese Academy of Medical Sciences (Yongjun Wang), and the Chinese Institute for Brain Research (Yilong Wang), Beijing, the Department of Neurology, Weihai Wendeng District People's Hospital, Weihai (J.Z.), the Department of Neurology, Sui Chinese Medical Hospital, Shangqiu (Y.L.), the Department of Neurology, Qinghe People's Hospital, Xingtai (Y.Z.), the Department of Neurology, Biyang People's Hospital, Zhumadian (S.Z.), the Department of Neurology, Jiyuan Chinese Medical Hospital, Jiyuan (H.Y.), the Department of Neurology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an (J.Y.), the Department of Neurology, Affiliated Shuyang Hospital of Xuzhou Medical University, Suqian (Yuanwei Wang), the Department of Neurology, Mengzhou People's Hospital (D. Li), and the Department of Neurology, Xiuwu People's Hospital (G.K.), Jiaozuo, and the Department of Neurology, Hejian People's Hospital, Cangzhou (Yanxia Wang, D. Liu) - all in China; the Department of Neurology, University of California, San Francisco, San Francisco (S.C.J.); the Department of Neurology and Stroke Center, Assistance Publique-Hôpitaux de Paris, Bichat Hospital, INSERM Laboratory for Vascular Translational Science-Unité 1148, University of Paris, Paris (P.A.); the Population Health Research Institute, McMaster University, Hamilton, ON, Canada (P.A.); and the Stroke Trials Unit, Mental Health and Clinical Neuroscience, University of Nottingham, Nottingham, United Kingdom (P.M.B.).
• N. Engl. J. Med. 2023 Dec 28; 389 (26): 241324242413-2424.

BackgroundDual antiplatelet treatment has been shown to lower the risk of recurrent stroke as compared with aspirin alone when treatment is initiated early (≤24 hours) after an acute mild stroke. The effect of clopidogrel plus aspirin as compared with aspirin alone administered within 72 hours after the onset of acute cerebral ischemia from atherosclerosis has not been well studied.MethodsIn 222 hospitals in China, we conducted a double-blind, randomized, placebo-controlled, two-by-two factorial trial involving patients with mild ischemic stroke or high-risk transient ischemic attack (TIA) of presumed atherosclerotic cause who had not undergone thrombolysis or thrombectomy. Patients were randomly assigned, in a 1:1 ratio, within 72 hours after symptom onset to receive clopidogrel (300 mg on day 1 and 75 mg daily on days 2 to 90) plus aspirin (100 to 300 mg on day 1 and 100 mg daily on days 2 to 21) or matching clopidogrel placebo plus aspirin (100 to 300 mg on day 1 and 100 mg daily on days 2 to 90). There was no interaction between this component of the factorial trial design and a second part that compared immediate with delayed statin treatment (not reported here). The primary efficacy outcome was new stroke, and the primary safety outcome was moderate-to-severe bleeding - both assessed within 90 days.ResultsA total of 6100 patients were enrolled, with 3050 assigned to each trial group. TIA was the qualifying event for enrollment in 13.1% of the patients. A total of 12.8% of the patients were assigned to a treatment group no more than 24 hours after stroke onset, and 87.2% were assigned after 24 hours and no more than 72 hours after stroke onset. A new stroke occurred in 222 patients (7.3%) in the clopidogrel-aspirin group and in 279 (9.2%) in the aspirin group (hazard ratio, 0.79; 95% confidence interval [CI], 0.66 to 0.94; P = 0.008). Moderate-to-severe bleeding occurred in 27 patients (0.9%) in the clopidogrel-aspirin group and in 13 (0.4%) in the aspirin group (hazard ratio, 2.08; 95% CI, 1.07 to 4.04; P = 0.03).ConclusionsAmong patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause, combined clopidogrel-aspirin therapy initiated within 72 hours after stroke onset led to a lower risk of new stroke at 90 days than aspirin therapy alone but was associated with a low but higher risk of moderate-to-severe bleeding. (Funded by the National Natural Science Foundation of China and others; INSPIRES ClinicalTrials.gov number, NCT03635749.).Copyright © 2023 Massachusetts Medical Society.

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