{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T19:45:40Z","timestamp":1793303140893,"version":"4.5.0"},"reference-count":24,"publisher":"American Medical Association (AMA)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n Prior trials showed that dual antiplatelet therapy could reduce the risk of early new stroke in patients with acute mild ischemic stroke or transient ischemic attack (TIA) within 24 hours of symptom onset. However, it is currently uncertain whether dual antiplatelet therapy can reduce the risk of early new stroke in patients with a more delayed initiation time window.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To evaluate the efficacy and safety of clopidogrel and aspirin among patients with mild ischemic stroke or TIA when initiated within 24 hours, from more than 24 hours to 48 hours, and from more than 48 hours to 72 hours.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n The Intensive Statin and Antiplatelet Therapy for Acute High-Risk Intracranial or Extracranial Atherosclerosis randomized clinical trial was a double-blind, placebo-controlled, multicenter, 2-by-2 factorial randomized clinical trial conducted at 222 hospitals in China from September 17, 2018, to October 15, 2022. All patients with acute mild ischemic stroke and TIA were included in this subgroup analysis and categorized into 3 groups according to time from symptom onset to randomization (group 1: \u226424 hours; group 2: &amp;gt;24 to \u226448 hours; and group 3: &amp;gt;48 to 72 hours). Patients were followed up for 90 days.<\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n All patients received clopidogrel combined with aspirin (clopidogrel 300 mg loading dose on day 1, followed by 75 mg daily on days 2 to 90, and aspirin 100 to 300 mg on the first day, 100 mg daily for days 2 to 21, and then a matching aspirin placebo for days 22 to 90) or aspirin alone (100 to 300 mg on day 1 and then 100 mg daily for days 2 to 90) within 72 hours after symptom onset.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary outcome was new stroke (ischemic or hemorrhagic) within 90 days. The primary safety outcome was moderate-to-severe bleeding, according to Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries criteria.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n This analysis included a total of 6100 patients (3050 in the clopidogrel-aspirin group and 3050 in the aspirin group). The median age was 65 years (IQR, 57-71 years), and 3915 patients (64.2%) were male. In the population with time to randomization of 24 hours or less, stroke occurred in the next 90 days in 97 of 783 patients (12.4%); among those randomized from more than 24 hours to 48 hours, in 211 of 2552 patients (8.3%); and among those randomized from more than 48 hours to 72 hours, in 193 of 2765 patients (7.0%). The clopidogrel-aspirin group had a lower risk of new stroke within 90 days compared with the aspirin alone group both in patients with time to randomization of from 48 to 72 hours (5.8% vs 8.2%; hazard ratio [HR], 0.70 [95% CI, 0.53-0.94]), of more than 24 to 48 hours (7.6% vs 8.9%; HR, 0.85 [95% CI, 0.65-1.12]), and of 24 hours or less (11.5% vs 13.4%; HR, 0.83 [95% CI, 0.55-1.25]) (\n P<\/jats:italic>\n \u2009=\u2009.38 for interaction). Among those with time to randomization of more than 48 to 72 hours, moderate-to-severe bleeding occurred in 12 patients (0.9%) in the clopidogrel-aspirin group and in 6 patients (0.4%) in the aspirin-alone group (HR, 2.00 [95% CI, 0.73-5.43]), while moderate-to-severe bleeding in those with time to randomization of more than 24 hours to 48 hours occurred in 9 patients (0.7%) in the clopidogrel-aspirin group and in 4 patients (0.3%) in the aspirin-alone group (HR, 2.25 [95% CI, 0.68-7.39]) and in those with time to randomization of within 24 hours, occurred in 6 patients (1.5%) in the clopidogrel-aspirin group and in 3 patients (0.8%) in the aspirin-alone group (HR, 1.57 [95% CI, 0.36-6.83]) (\n P<\/jats:italic>\n \u2009=\u2009.92 for interaction).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this randomized clinical trial of antiplatelet therapy in China, patients with mild ischemic stroke or TIA had consistent benefit from dual antiplatelet therapy with clopidogrel and aspirin vs aspirin alone when initiated within 72 hours after symptom onset, with a similar increase in the risk of moderate-to-severe bleeding. Patients should receive dual antiplatelet therapy with clopidogrel and aspirin within 72 hours after symptom onset.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT03635749<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2024.31938","type":"journal-article","created":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T11:36:11Z","timestamp":1725622571000},"page":"e2431938","source":"Crossref","is-referenced-by-count":14,"title":["Clopidogrel and Aspirin Initiated Between 24 to 72 Hours for Mild Ischemic Stroke"],"prefix":"10.1001","volume":"7","author":[{"given":"Yuetong","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinguo","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Weihai Wendeng District People\u2019s Hospital, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiqi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Claiborne","family":"Johnston","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California, San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip M.","family":"Bath","sequence":"additional","affiliation":[{"name":"Stroke Trials Unit, Division of Mental Health and Clinical Neuroscience, University of Nottingham, Nottingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Amarenco","sequence":"additional","affiliation":[{"name":"Department of Neurology and Stroke Center, Bichat Hospital, Assistance Publique\u2013H\u00f4pitaux de Paris, University of Paris, Paris, France"},{"name":"Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyi","family":"Yan","sequence":"additional","affiliation":[{"name":"China National Clinical Research Center for Neurological Diseases, 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Capital Medical University, Beijing, China"},{"name":"China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medican University, Beijing, China"},{"name":"Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China"},{"name":"National Center for Neurological Disorders, Shanghai, China"},{"name":"Research Unit of Artificial Intelligence in Cerebrovascular Disease, Chinese Academy of Medical Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuesong","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China"},{"name":"China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medican University, Beijing, 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