近日，PEARL研究组报道了大血管闭塞急性缺血性卒中患者行取栓术后进行动脉内阿替普酶的临床益处。这一研究成果于2025年10月13日发表《美国医学会杂志》上。

大血管闭塞急性缺血性卒中患者行取栓术后的功能预后仍不理想，取栓后动脉内阿替普酶的益处仍不确定。

为了探讨血管内再灌注成功后动脉内阿替普酶治疗是否能改善急性前循环大血管闭塞性卒中患者的功能预后，研究组进行了一项多中心随机临床试验，招募了在症状出现24小时内实现再灌注成功（脑梗死扩大溶栓评分≥2b50）的前循环大血管闭塞性卒中患者。允许基于指南的静脉溶栓。患者在2023年8月1日至2024年10月16日之间随机分组，试验在中国28家医院进行。最终随访时间为2025年1月7日。

动脉内阿替普酶治疗（n=164）与标准治疗（n = 160）相比，剂量为0.225 mg/kg（最大剂量为20 mg）。主要结局是90天时改良Rankin量表评分为0或1的患者比例（评分范围为0[无症状]至6[死亡]；0或1分表示预后良好）。安全性结局包括随机分组后36小时内出现症状性颅内出血，90天内全因死亡率，以及36小时内出现颅内出血。

在随机分组的324例患者中（中位年龄68岁[IQR， 58-75岁]，女性99例[30.6%]），每组1例患者失访。动脉内阿替普酶组90天改良Rankin量表评分为0或1分的患者比例为44.8%(73/163)，而标准治疗组为30.2%(48/159)（校正风险比[RR]， 1.45; P = 0.01）。动脉内阿替普酶组36小时内出现症状性颅内出血的患者比例为4.3%(7/164)，而标准治疗组为5.0%(8/160)（调整后RR为0.85;P = 0.67）。动脉内阿替普酶治疗组90天内全因死亡率为17.1%(28/164)，标准治疗组为11.3%(18/160)（校正风险比为1.60；P = 0.12）。动脉内阿替普酶组在36小时内出现颅内出血的患者比例为32.9%(54/164)，而标准治疗组为26.9%(43/160)（调整后RR为1.22：P = 0.17）。

研究结果表明，在通过机械取栓成功实现血管内再灌注的急性前循环大血管闭塞性卒中患者中，动脉内阿替普酶在90天内获得良好预后的可能性更高。接受动脉内阿替普酶治疗的患者的全因死亡率和颅内出血发生率较高，尽管这些差异没有统计学意义。

附：英文原文

Title: Intra-Arterial Alteplase After Successful Endovascular Reperfusion in Acute Stroke: The PEARL Randomized Clinical Trial

Author: Writing Committee for the PEARL Investigators, Aoming Jin, Bing Sun, Chengbo Dai, Hongbing Chen, Hongyu Qiao, Jinsong You, Kangning Chen, Shuo Wang, Weihua Deng, Xu Tong, Yueqi Zhu, Zhong Ji, Xinguang Yang, Xiongjun He, Yongteng Xu, Dong Pan, Kaifeng Li, Yanting Chen, Yingying Zhu, Yuesong Pan, Tingyu Yi, Min Zhang, Huiyuan Peng, Weidong Huang, Dengxing Li, Jiyun Feng, Junbin Chen, Weiheng Lu, Bin Liao, Yituan Xie, Baogong Liao, Lei Yang, Longchong Tang, Bin Han, Yanchao Liu, Peijian Lin, Jixing Chen, Yanling Liang, Di Li, Guohu Weng, Hanning Huang, Hao Li, Chaoqun Li, Zhiqiang Peng, Hongzhuang Li, Baixuan He, Ruiqi Xue, Mingyi Bao, Haoyang Sun, Hongbiao Hou, Hongxing Zhou, Yibin Xiao, Jie Li, Wanzhou Zhang, Xi Chen, Wei Yan, Yaxuan Pi, Zhenhong Deng, Jinyuan Wang, Dongshu Xie, Mengqi Liu, Honghong Li, Qingxia Peng, Wenli Fang, Xuejing Lin, Ziyi Chen, Haiwei Li, Yuxi Lin, Queran Lin, Songhua Xiao, Zhongrong Miao, Duolao Wang, Thanh N. Nguyen

Issue&Volume: 2025-10-13

Abstract:

Importance  Functional outcomes in patients with acute ischemic stroke due to large-vessel occlusion who undergo thrombectomy remain suboptimal, and the benefits of intra-arterial alteplase after thrombectomy remain uncertain.

Objective  To investigate whether treatment with intra-arterial alteplase after successful endovascular reperfusion improves functional outcomes among patients with acute, anterior-circulation, large-vessel occlusion stroke.

Design, Setting, and Participants  This multicenter, randomized clinical trial recruited patients with anterior-circulation, large-vessel occlusion stroke within 24 hours of symptom onset who achieved successful reperfusion (expanded Thrombolysis in Cerebral Infarction scale score of ≥2b50) after thrombectomy. Guideline-based intravenous thrombolysis was allowed. Patients were randomized between August 1, 2023, and October 16, 2024, and the trial was conducted at 28 hospitals in China. Final follow-up occurred on January 7, 2025.

Interventions  Intra-arterial alteplase treatment (n=164) with 0.225 mg/kg (maximum dose of 20 mg) vs standard treatment (n=160).

Main Outcomes and Measures  The primary outcome was the proportion of patients with a modified Rankin Scale score of 0 or 1 at 90 days (score range, 0 [no symptoms] to 6 [death]; a score of 0 or 1 indicates an excellent outcome). The safety outcomes included symptomatic intracranial hemorrhage within 36 hours of randomization, all-cause mortality within 90 days, and any intracranial hemorrhage within 36 hours.

Results  Of the 324 patients randomized (median age, 68 years [IQR, 58-75 years]; 99 were female [30.6%]), 1 patient in each group was lost to follow-up. The proportion of patients with a modified Rankin Scale score of 0 or 1 at 90 days was 44.8% (73/163) in the intra-arterial alteplase group vs 30.2% (48/159) in the standard treatment group (adjusted risk ratio [RR], 1.45 [95% CI, 1.08-1.96]; P=.01). The proportion of patients with symptomatic intracranial hemorrhage within 36 hours was 4.3% (7/164) in the intra-arterial alteplase group vs 5.0% (8/160) in the standard treatment group (adjusted RR, 0.85 [95% CI, 0.43-1.69]; P=.67). The proportion of patients with all-cause mortality within 90 days was 17.1% (28/164) in the intra-arterial alteplase group vs 11.3% (18/160) in the standard treatment group (adjusted hazard ratio, 1.60 [95% CI, 0.88-2.89]; P=.12). The proportion of patients with any intracranial hemorrhage within 36 hours was 32.9% (54/164) in the intra-arterial alteplase group vs 26.9% (43/160) in the standard treatment group (adjusted RR, 1.22 [95% CI, 0.92-1.63]; P=.17).

Conclusions and Relevance  Among patients with acute, anterior-circulation, large-vessel occlusion stroke who achieved successful endovascular reperfusion by mechanical thrombectomy, intra-arterial alteplase resulted in a higher likelihood of excellent outcomes at 90 days. The incidence of all-cause mortality and any intracranial hemorrhage was higher in patients who received intra-arterial alteplase, although these differences were not statistically significant.

DOI: 10.1001/jama.2025.16876

Source: https://jamanetwork.com/journals/jama/fullarticle/2839937