Intra-Arterial Alteplase After Successful Endovascular Reperfusion in Acute Stroke

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. Trial Registration ClinicalTrials.gov Identifier: NCT05856851

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Journal
JAMA
Published
2025-10-13
DOI
https://doi.org/10.1001/jama.2025.16876
Citations
4
Primary Topic
Acute Ischemic Stroke Management
Type
article
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5.42
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article

Intra-Arterial Alteplase After Successful Endovascular Reperfusion in Acute Stroke

Queran Lin, Zhiqiang Peng, Thanh N. Nguyen, Zhongrong Miao et al.
4 citations
JAMA
Acute Ischemic Stroke Management
5.42
article

Intra-Arterial Alteplase After Successful Endovascular Reperfusion in Acute Stroke

Queran Lin, Zhiqiang Peng, Thanh N. Nguyen, Zhongrong Miao, Rui Xue, Yituan Xie, Jixing Chen, Xuejing Lin, Yi-Bin Xiao, Hongzhuang Li, Huiyuan Peng, Weiheng Lu, Qingxia Peng, Zhenhong Deng, Hongyu Qiao, Xinguang Yang, Yanling Liang, Hanning Huang, Huan‐Xiang Zhou, Wanzhou Zhang, Haiwei Li, Di Li, Yaxuan Pi, Yingying Zhu, L.Q. Tang, Yongteng Xu, Haoyang Sun, Dan Xie, Yuesong Pan, J Wang, Mengmeng Bao, Bing Liao, Weidong Huang, Guohu Weng, Kangning Chen, Dong Pan, Aoming Jin, Yajie Liu, Yueqi Zhu, Hao Li, Ziyi Chen, Min Zhang, Jie Li, Xu Tong, Weihua Deng, Wei Yan, Hongbing Chen, Yuxi Lin, Songhua Xiao, Chaoqun Li, Mengqi Liu, Yanting Chen, Bin Han, Zhong Ji, Baixuan He, Xiongjun He, Bing Sun, Peijian Lin, Shuo Wang, Jinsong You, Kaifeng Li, Honghong Li, Lei Yang, Junbin Chen, Yanchao Liu, Wenli Fang, Jiyun Feng, Xi Chen, Yamei Tang, Tingyu Yi, Chengbo Dai, D. Li, Hongbiao Hou, Bin Liao, Duolao Wang, Raul G. Nogueira
article en
4 citations

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. Trial Registration ClinicalTrials.gov Identifier: NCT05856851

JAMAVol. 334(19)
Boston University (US), Guangzhou University of Chinese Medicine (CN), Boston Medical Center (US), Fujian Medical University (CN), Sun Yat-sen University (CN), University of Pittsburgh (US), Guilin Medical University (CN), Capital Medical University (CN), Liverpool School of Tropical Medicine (GB), Dalian University of Technology (CN), Shantou University (CN), Beijing Tian Tan Hospital (CN), Xinhui People's Hospital (CN), Third Affiliated Hospital of Guangzhou Medical University (CN), Ganzhou People's Hospital (CN), Sun Yat-sen Memorial Hospital (CN), The First People's Hospital of Shunde (CN), UPMC Health System (US), Central People's Hospital of Zhanjiang (CN), Zhangzhou Municipal Hospital of Fujian Province (CN), Dalian Municipal Central Hospital (CN), Yue Bei People's Hospital (CN), Songshan Lake Materials Laboratory (CN), Zhujiang Hospital (CN), Pearl River Hydraulic Research Institute (CN), Panyu District Central Hospital (CN), Zhongshan Hospital (CN), Fourth Affiliated Hospital of Guangxi Medical University (CN), Second Affiliated Hospital of Fujian Medical University (CN), University of Pittsburgh Medical Center (US), Huizhou Central People's Hospital (CN), Baise University (CN), Southern Medical University Shenzhen Hospital (CN), The First People's Hospital of Zhaoqing (CN), Hainan Provincial Hospital of Traditional Chinese Medicine (CN), Liaocheng People's Hospital (CN), Gaozhou People's Hospital (CN), Guhua Hospital (CN), Eighth Affiliated Hospital of Sun Yat-sen University, Imperial College London (GB), Southern Medical University (CN), Guangzhou Medical University (CN), Huizhou University (CN)
Openalex Percentile: Top 4%
Acute Ischemic Stroke Management
5.42
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