Lin Longting, Liu Feifeng, Yi Tingyu, Zhu Yueqi, Yang Jianhong, Zhao Yanxin, Wang Feng, Xiang Guangyu, Chen Chen, Xiao Yaping, Shen Hao, Xu Luran, Long Yuming, Zhang Yue, Huang Zhengyu, Chen Chushuang, Churilov Leonid, Parsons Mark W, Chen Wenhuo, Li Gang
Department of Neurology, Shanghai East Hospital, Tongji University School of Medicine, Tongji University, Shanghai, China.
Sino-Australian Neurological Clinical Research Cooperation Centre, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
JAMA Netw Open. 2025 Apr 1;8(4):e255308. doi: 10.1001/jamanetworkopen.2025.5308.
Tirofiban is a nonpeptide antagonist of the glycoprotein IIb/IIIa receptor that inhibits platelet aggregation selectively. Despite widespread use in acute ischemic stroke in conjunction with endovascular treatment, the role of tirofiban is uncertain.
To assess whether intravenous tirofiban initiated before endovascular thrombectomy improves thrombectomy outcomes by achieving first-pass recanalization without intracranial hemorrhagic risk.
DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter, prospective, open-label, blinded, end point phase 2 randomized clinical trial that enrolled patients from 7 Chinese hospital stroke centers between April 30, 2021, and July 16, 2023. Eligible patients were aged 18 to 85 years with large vessel occlusion (internal carotid artery or M1 or M2 segment of middle cerebral artery) and were considered for endovascular thrombectomy within 24 hours of ischemic stroke onset or last known well time. Patients with a history of atrial fibrillation or treated with intravenous thrombolysis were excluded.
Patients were randomly assigned (1:1) to intravenous tirofiban (10 μg/kg bolus plus 0.1 μg/kg per minute infusion for 24 hours) or standard care before endovascular thrombectomy using a web-based, computer-generated randomization procedure.
The primary outcome was the proportion of patients achieving first-pass recanalization without symptomatic intracranial hemorrhage. First-pass recanalization was assessed by reviewers blinded to treatment allocation and predefined as successful recanalization of a targeted vessel after a single pass of thrombectomy. The primary outcome was analyzed by modified Poisson regression with robust error estimation, adjusting for time from onset or last known well time to randomization and vessel occlusion site.
Among 200 patients randomized (median age, 66 years [IQR, 58-72 years]; 146 male [73%]), 102 were allocated to receive intravenous tirofiban, and 98 were allocated to receive standard care before endovascular thrombectomy. In the intention-to-treat analysis, 64 of 99 patients receiving tirofiban (65%) and 46 of 95 control patients (48%) achieved the primary outcome of first-pass recanalization without symptomatic intracranial hemorrhage (adjusted risk ratio, 1.34 [95% CI, 1.04-1.73]; P = .03). Incidence of symptomatic intracranial hemorrhage was 0% (0 of 101 patients) in the tirofiban group vs 6% (6 of 98 patients) in the control group (unadjusted risk difference, -0.06 [95% CI, -0.11 to -0.01]).
In this randomized clinical trial of patients who had acute ischemic stroke with no history of atrial fibrillation and no prior intravenous thrombolysis, intravenous tirofiban administered before endovascular thrombectomy increased the likelihood of first-pass recanalization without symptomatic intracranial hemorrhage. These findings suggest that neurointerventionalists may consider this pre-procedure antiplatelet treatment to facilitate endovascular thrombectomy.
ClinicalTrials.gov Identifier: NCT04851457.
替罗非班是一种糖蛋白IIb/IIIa受体的非肽类拮抗剂，可选择性抑制血小板聚集。尽管其在急性缺血性卒中与血管内治疗联合应用中广泛使用，但其作用尚不确定。
评估血管内血栓切除术前行静脉注射替罗非班能否通过实现首次通过再通且无颅内出血风险来改善血栓切除术的结果。
设计、地点和参与者：这是一项多中心、前瞻性、开放标签、盲终点的2期随机临床试验，于2021年4月30日至2023年7月16日从7家中国医院卒中中心招募患者。符合条件的患者年龄在18至85岁之间，患有大血管闭塞（颈内动脉或大脑中动脉M1或M2段），并在缺血性卒中发作或最后已知良好时间的24小时内考虑进行血管内血栓切除术。排除有房颤病史或接受过静脉溶栓治疗的患者。
患者通过基于网络的计算机生成随机程序被随机分配（1:1）接受静脉注射替罗非班（10μg/kg推注加0.1μg/kg每分钟输注24小时）或血管内血栓切除术前行标准护理。
主要结局是实现首次通过再通且无症状性颅内出血的患者比例。首次通过再通由对治疗分配不知情的审查员评估，并预先定义为血栓切除术单次通过后目标血管成功再通。主要结局通过具有稳健误差估计的修正泊松回归分析，调整从发作或最后已知良好时间到随机分组的时间以及血管闭塞部位。
在200例随机分组的患者中（中位年龄66岁[四分位间距，58 - 72岁]；146例男性[73%]），102例被分配接受静脉注射替罗非班，98例被分配接受血管内血栓切除术前行标准护理。在意向性分析中，接受替罗非班的99例患者中有64例（65%）以及95例对照患者中有46例（48%）实现了首次通过再通且无症状性颅内出血的主要结局（调整风险比，1.34[95%置信区间，1.04 - 1.73]；P = 0.03）。替罗非班组症状性颅内出血发生率为0%（101例患者中0例），而对照组为6%（98例患者中6例）（未调整风险差异，-0.06[95%置信区间，-0.11至-0.01]）。
在这项针对无房颤病史且未接受过静脉溶栓治疗的急性缺血性卒中患者的随机临床试验中，血管内血栓切除术前行静脉注射替罗非班增加了首次通过再通且无症状性颅内出血的可能性。这些发现表明神经介入医生可能会考虑这种术前抗血小板治疗以促进血管内血栓切除术。
ClinicalTrials.gov标识符：NCT04851457。
