Effect of Argatroban Plus Intravenous Alteplase vs Intravenous Alteplase Alone on Neurologic Function in Patients With Acute Ischemic Stroke

作者：Dawei Chen, Yu Cui, Zhonghe Zhou, Ying-Jie Dai, Gaohua Li, Zhaolong Peng, Yi Zhang, Xiaodong Liu, Zhi-Mei Yuan, Changhao Jiang, Qingcheng Yang, Ying-Jie Duan, Guang-Bin Ma, Liwei Zhao, Ruixian Wang, Yuanlin Sun, Lei Shen, Er-Qiang Wang, Lihua Wang, Ye-Fang Feng, Fengyun Wang, Ren-Lin Zou, Heping Yang, Kai Wang, Duolao Wang, Yilong Wang, ARAIS Investigators, Xuewen Liu, Zilong Chen, Ming-Zhe Yu, Shuman Huang, Lian-Qiang Wang, Shi-Mei Geng, Shi-Huo Chen, Wei-Zhong Wang, Ming Zou, L X Hu, Dan Wang, Shiyong Zhang, Zai-Hui Zhang, Zhao Jiang, Liyun Wang, Sufang Wu, Run-Hui Li, Yongsheng Wang, Min Yu, Li Liu, Kui-Hua Yang, Hui Li, Haijun Wang, Jun-Hai Wang, Runxiu Zhu, Guoqiang Wen, Yongjun Cao, Qi-Da Zhou, Wenhai Yang · 发表于：JAMA · 年份：2023 · DOI：10.1001/jama.2023.0550 · 被引用次数：66 · 研究领域：Acute Ischemic Stroke Management、S100 Proteins and Annexins、Intracerebral and Subarachnoid Hemorrhage Research

Importance: Previous studies suggested a benefit of argatroban plus alteplase (recombinant tissue-type plasminogen activator) in patients with acute ischemic stroke (AIS). However, robust evidence in trials with large sample sizes is lacking. Objective: To assess the efficacy of argatroban plus alteplase for AIS. Design, Setting, and Participants: This multicenter, open-label, blinded end point randomized clinical trial including 808 patients with AIS was conducted at 50 hospitals in China with enrollment from January 18, 2019, through October 30, 2021, and final follow-up on January 24, 2022. Interventions: Eligible patients were randomly assigned within 4.5 hours of symptom onset to the argatroban plus alteplase group (n = 402), which received intravenous argatroban (100 μg/kg bolus over 3-5 minutes followed by an infusion of 1.0 μg/kg per minute for 48 hours) within 1 hour after alteplase (0.9 mg/kg; maximum dose, 90 mg; 10% administered as 1-minute bolus, remaining infused over 1 hour), or alteplase alone group (n = 415), which received intravenous alteplase alone. Both groups received guideline-based treatments. Main Outcomes and Measures: The primary end point was excellent functional outcome, defined as a modified Rankin Scale score (range, 0 [no symptoms] to 6 [death]) of 0 to 1 at 90 days. All end points had blinded assessment and were analyzed on a full analysis set. Results: Among 817 eligible patients with AIS who were randomized (median [IQR] age, 65 [57-71] year...