Chen Hui-Sheng, Cui Yu, Wang Xin-Hong, Ma Yu-Tong, Han Jing, Duan Ying-Jie, Lu Jiang, Shen Li-Ying, Liang Yong, Wang Wei-Zhong, Wang Hui, Zhao Yong, Zhang Jin-Tao, Song Yu-Lin, He Xiao-Mei, Li Run-Hui, Tao Ding-Bo, Li Jing, Huang Shu-Man, Wang Ni, Hong Mei, Meng Chong, Zhang Wei, Wang Duo-Lao, Nguyen Thanh N
Department of Neurology, General Hospital of Northern Theatre Command, Shenyang, China.
Department of Neurology, Beipiao Central Hospital, Beipiao, China.
JAMA Neurol. 2024 May 1;81(5):450-460. doi: 10.1001/jamaneurol.2024.0146.
Dual antiplatelet therapy has been demonstrated to be superior to single antiplatelet in reducing recurrent stroke among patients with transient ischemic attack or minor stroke, but robust evidence for its effect in patients with mild to moderate ischemic stroke is lacking.
To evaluate whether dual antiplatelet therapy is superior to single antiplatelet among patients with mild to moderate ischemic stroke.
DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter, open-label, blinded end point, randomized clinical trial conducted at 66 hospitals in China from December 20, 2016, through August 9, 2022. The date of final follow-up was October 30, 2022. The analysis was reported on March 12, 2023. Of 3065 patients with ischemic stroke, 3000 patients with acute mild to moderate stroke within 48 hours of symptom onset were enrolled, after excluding 65 patients who did not meet eligibility criteria or had no randomization outcome.
Within 48 hours after symptom onset, patients were randomly assigned to receive clopidogrel plus aspirin (n = 1541) or aspirin alone (n = 1459) in a 1:1 ratio.
The primary end point was early neurologic deterioration at 7 days, defined as an increase of 2 or more points in National Institutes of Health Stroke Scale (NIHSS) score, but not as a result of cerebral hemorrhage, compared with baseline. The superiority of clopidogrel plus aspirin to aspirin alone was assessed based on a modified intention-to-treat population, which included all randomized participants with at least 1 efficacy evaluation regardless of treatment allocation. Bleeding events were safety end points.
Of the 3000 randomized patients, 1942 (64.6%) were men, the mean (SD) age was 65.9 (10.6) years, median (IQR) NIHSS score at admission was 5 (4-6), and 1830 (61.0%) had a stroke of undetermined cause. A total of 2915 patients were included in the modified intention-to-treat analysis. Early neurologic deterioration occurred in 72 of 1502 (4.8%) in the dual antiplatelet therapy group vs 95 of 1413 (6.7%) in the aspirin alone group (risk difference -1.9%; 95% CI, -3.6 to -0.2; P = .03). Similar bleeding events were found between 2 groups.
Among Chinese patients with acute mild to moderate ischemic stroke, clopidogrel plus aspirin was superior to aspirin alone with regard to reducing early neurologic deterioration at 7 days with similar safety profile. These findings indicate that dual antiplatelet therapy may be a superior choice to aspirin alone in treating patients with acute mild to moderate stroke.
ClinicalTrials.gov Identifier: NCT02869009.
在短暂性脑缺血发作或轻度卒中患者中，双重抗血小板治疗已被证明在降低复发性卒中方面优于单一抗血小板治疗，但在轻度至中度缺血性卒中患者中其疗效缺乏有力证据。
评估双重抗血小板治疗在轻度至中度缺血性卒中患者中是否优于单一抗血小板治疗。
设计、地点和参与者：这是一项多中心、开放标签、终点设盲的随机临床试验，于2016年12月20日至2022年8月9日在中国66家医院进行。最终随访日期为2022年10月30日。分析报告于2023年3月12日发布。在3065例缺血性卒中患者中，纳入了3000例症状发作后48小时内的急性轻度至中度卒中患者，排除了65例不符合纳入标准或无随机分组结果的患者。
症状发作后48小时内，患者按1:1比例随机分配接受氯吡格雷联合阿司匹林治疗（n = 1541）或单独使用阿司匹林治疗（n = 1459）。
主要终点为7天时的早期神经功能恶化，定义为与基线相比，美国国立卫生研究院卒中量表（NIHSS）评分增加2分或更多分，但并非由脑出血导致。基于改良意向性治疗人群评估氯吡格雷联合阿司匹林相对于单独使用阿司匹林的优越性，该人群包括所有至少有1次疗效评估的随机参与者，无论治疗分配情况如何。出血事件为安全性终点。
在3000例随机分组的患者中，1942例（64.6%）为男性，平均（标准差）年龄为65.9（10.6）岁，入院时NIHSS评分中位数（四分位间距）为5（4 - 6），1830例（61.0%）卒中病因不明。共有2915例患者纳入改良意向性治疗分析。双重抗血小板治疗组1502例中有72例（4.8%）发生早期神经功能恶化，而单独使用阿司匹林组1413例中有95例（6.7%）发生早期神经功能恶化（风险差异 -1.9%；95%置信区间，-3.6至 -0.2；P = 0.03）。两组间出血事件相似。
在中国急性轻度至中度缺血性卒中患者中，氯吡格雷联合阿司匹林在降低7天时的早期神经功能恶化方面优于单独使用阿司匹林，且安全性相似。这些发现表明，双重抗血小板治疗在治疗急性轻度至中度卒中患者时可能是优于单独使用阿司匹林的选择。
ClinicalTrials.gov标识符：NCT02869009。
