缺血性脑卒中后 72 小时内的双联抗血小板治疗。
Dual Antiplatelet Treatment up to 72 Hours after Ischemic Stroke.
机构信息
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.).
出版信息
N Engl J Med. 2023 Dec 28;389(26):2413-2424. doi: 10.1056/NEJMoa2309137.
BACKGROUND
Dual 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.
METHODS
In 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.
RESULTS
A 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).
CONCLUSIONS
Among 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.).
背景
与单独使用阿司匹林相比，在急性轻度中风后尽早（≤24 小时）开始双联抗血小板治疗可降低复发性中风的风险。在动脉粥样硬化引起的急性大脑缺血发作后 72 小时内，氯吡格雷联合阿司匹林与单独使用阿司匹林相比的效果尚未得到很好的研究。
方法
在中国的 222 家医院中，我们进行了一项双盲、随机、安慰剂对照、两因素、2×2 析因试验，纳入了未接受溶栓或取栓治疗的轻度缺血性中风或有高风险短暂性脑缺血发作（TIA）的患者，这些患者的病因被认为是动脉粥样硬化。患者在症状发作后 72 小时内，以 1:1 的比例随机分配，接受氯吡格雷（第 1 天 300 mg，第 2 天至第 90 天每天 75 mg）联合阿司匹林（第 1 天 100-300 mg，第 2 天至第 21 天每天 100 mg）或匹配的氯吡格雷安慰剂联合阿司匹林（第 1 天 100-300 mg，第 2 天至第 90 天每天 100 mg）。该析因试验设计的这一部分与第二部分没有相互作用，第二部分比较了即刻与延迟使用他汀类药物的治疗效果（此处未报告）。主要疗效结局是新发中风，主要安全性结局是中度至重度出血-均在 90 天内评估。
结果
共有 6100 名患者入组，每组 3050 名。TIA 是患者入组的合格事件，占 13.1%。共有 12.8%的患者在中风发作后不超过 24 小时被分配到治疗组，87.2%的患者在中风发作后 24 小时至 72 小时内被分配到治疗组。氯吡格雷-阿司匹林组有 222 名（7.3%）患者发生新发中风，阿司匹林组有 279 名（9.2%）患者发生新发中风（风险比，0.79；95%置信区间[CI]，0.66 至 0.94；P=0.008）。氯吡格雷-阿司匹林组有 27 名（0.9%）患者发生中度至重度出血，阿司匹林组有 13 名（0.4%）患者发生中度至重度出血（风险比，2.08；95%CI，1.07 至 4.04；P=0.03）。
结论
在轻度缺血性中风或有高风险动脉粥样硬化性 TIA 的患者中，在中风发作后 72 小时内开始的氯吡格雷联合阿司匹林治疗与单独使用阿司匹林相比，90 天内新发中风的风险较低，但中度至重度出血的风险较低，但更高。（由国家自然科学基金委员会等资助；INSPIRES ClinicalTrials.gov 编号，NCT03635749。）
Zotero 插件