Research Progress on the Effect of Intra-Arterial Thrombolysis on Improving Functional Outcomes Following Successful Endovascular Treatment

doi:10.3969/j.issn.1673-5765.2025.10.013

Abstract

Abstract: Endovascular treatment, as the first-line treatment for acute ischemic stroke with large vessel occlusion, achieves a successful recanalization rate of over 80%, yet half failed to achieve good functional outcome at 90 days, indicating the prevalence of futile recanalization. No-reflow phenomenon and early arterial reocclusion, both closely associated with post-procedural thrombotic burden, are the core mechanisms underlying futile recanalization after endovascular treatment. Intra-arterial thrombolysis after endovascular treatment can clear residual thrombi and improve microcirculatory perfusion in brain tissue, holding promise for further enhancing functional outcomes in acute ischemic stroke with large vessel occlusion patients. In 2022, after the publication of the chemical optimization of cerebral embolectomy in patients with acute stroke treated with mechanical thrombectomy (CHOICE) trial, subsequent studies exploring the efficacy of intra-arterial thrombolysis after endovascular treatment or the optimal dosage of thrombolytic agents have been initiated. However, due to differences in key design elements across these studies, their results exhibit significant heterogeneity. This article reviews the research progress on intra-arterial thrombolysis after endovascular treatment, discusses its potential value in improving the functional outcomes of patients with acute ischemic stroke with large vessel occlusion, and aims to provide clinicians and researchers with a reference for clinical decision-making and insights for relevant research design.

Key words: Endovascular treatment; Intra-arterial thrombolysis; Functional outcome; No-reflow phenomenon; Futile recanalization

摘要： 血管内治疗作为急性大血管闭塞性缺血性卒中的一线治疗措施，能实现80%以上的血管再通率。但血管内治疗后无效再通问题突出，约50%的患者无法获得良好功能预后。无复流现象和早期动脉再闭塞是血管内治疗后无效再通的核心机制，且两者均与术后血栓负荷密切相关。血管内治疗反桥接动脉溶栓可清除残余血栓并改善脑组织的微循环灌注，有望进一步改善急性大血管闭塞性缺血性卒中患者的功能预后。2022年，机械取栓治疗急性卒中血栓栓塞药物优化（chemical optimization of cerebral embolectomy in patients with acute stroke treated with mechanical thrombectomy，CHOICE）研究结果公布后，多项探索血管内治疗反桥接动脉溶栓有效性及溶栓药物最佳剂量的研究相继开展。然而，由于不同研究的关键设计要素存在差异，其结果具有明显的异质性。本文对血管内治疗后反桥接动脉溶栓相关研究进展进行综述，探讨该治疗技术改善急性大血管闭塞性缺血性卒中患者功能预后的潜在价值，以期为临床医师和研究者提供治疗决策参考和相关研究设计思路。

关键词: 血管内治疗; 动脉溶栓; 功能预后; 无复流现象; 无效再通

CLC Number:

SHEN Kejia, WANG Liyuan, XIONG Yunyun. Research Progress on the Effect of Intra-Arterial Thrombolysis on Improving Functional Outcomes Following Successful Endovascular Treatment[J]. Chinese Journal of Stroke, 2025, 20(10): 1308-1317.

沈柯佳, 王利圆, 熊云云. 缺血性卒中血管内治疗后时代：反桥接动脉溶栓研究进展[J]. 中国卒中杂志, 2025, 20(10): 1308-1317.

References

[1] MALHOTRA K，GORNBEIN J，SAVER J L. Ischemic strokes due to large-vessel occlusions contribute disproportionately to stroke-related dependence and death：a review[J/OL]. Front Neurol，2017，8：651[2025-03-07]. https://doi.org/10.3389/fneur.2017.00651.
[2] GOYAL M，MENON B K，VAN ZWAM W H，et al. Endovascular thrombectomy after large-vessel ischaemic stroke：a meta-analysis of individual patient data from five randomised trials[J]. Lancet，2016，387（10029）：1723-1731.
[3] GILES J A，VELLIMANA A K，ADEOYE O M. Endovascular treatment of acute stroke[J]. Curr Neurol Neurosci Rep，2022，22（1）：83-91.
[4] POWERS W J，DERDEYN C P，BILLER J，et al. 2015 American Heart Association/American Stroke Association focused update of the 2013 guidelines for the early management of patients with acute ischemic stroke regarding endovascular treatment[J]. Stroke，2015，46（10）：3020-3035.
[5] NOGUEIRA R G，JADHAV A P，HAUSSEN D C，et al. Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct[J]. N Engl J Med，2018，378（1）：11-21.
[6] ALBERS G W，MARKS M P，KEMP S，et al. Thrombectomy for stroke at 6 to 16 hours with selection by perfusion imaging[J]. N Engl J Med，2018，378（8）：708-718.
[7] MUJANOVIC A，NG F，MEINEL T R，et al. No-reflow phenomenon in stroke patients：a systematic literature review and meta-analysis of clinical data[J]. Int J Stroke，2024，19（1）：58-67.
[8] NG F C，CHURILOV L，YASSI N，et al. Prevalence and significance of impaired microvascular tissue reperfusion despite macrovascular angiographic reperfusion（no-reflow）[J/OL]. Neurology，2022，98（8）：e790-e801[2025-03-07]. https://doi.org/10.1212/WNL.0000000000013210.
[9] SPERRING C P，SAVAGE W M，ARGENZIANO M G，et al. No-reflow post-recanalization in acute ischemic stroke：mechanisms，measurements，and molecular markers[J]. Stroke，2023，54（9）：2472-2480.
[10] EL AMKI M，WEGENER S. Improving cerebral blood flow after arterial recanalization：a novel therapeutic strategy in stroke[J/OL]. Int J Mol Sci，2017，18（12）：2669[2025-03-07]. https://doi.org/10.3390/ijms18122669.
[11] RENÚ A，MILLÁN M，SAN ROMÁN L，et al. Effect of intra-arterial alteplase vs. placebo following successful thrombectomy on functional outcomes in patients with large vessel occlusion acute ischemic stroke：the CHOICE randomized clinical trial[J]. JAMA，2022，327（9）：826-835.
[12] LIU C，GUO C W，LI F L，et al. Intra-arterial urokinase after endovascular reperfusion for acute ischemic stroke：the POST-UK randomized clinical trial[J]. JAMA，2025，333（7）：589-598.
[13] HUANG J C，YANG J，LIU C，et al. Intra-arterial tenecteplase following endovascular reperfusion for large vessel occlusion acute ischemic stroke：the POST-TNK randomized clinical trial[J]. JAMA，2025，333（7）：579-588.
[14] MIAO Z R，LUO G，SONG L G，et al. Intra-arterial tenecteplase for acute stroke after successful endovascular therapy：the ANGEL-TNK randomized clinical trial[J]. JAMA，2025，334（7）：582-591.
[15] Writing Committee for the PEARL Investigators，PEARL Investigators. Intra-arterial alteplase after successful endovascular reperfusion in acute stroke：the PEARL randomized clinical trial[J/OL]. JAMA，2025[2025-10-17]. https://doi.org/10.1001/jama.2025.16876.
[16] HOU X H，HUANG J C，WANG L，et al. Intra-arterial tenecteplase after successful reperfusion in large vessel occlusion stroke：a randomized clinical trial[J]. JAMA Neurol，2025，82（9）：895-904.
[17] HU W，TAO C R，WANG L，et al. Intra-arterial tenecteplase after successful endovascular recanalisation in patients with acute posterior circulation arterial occlusion（ATTENTION-IA）：multicentre randomised controlled trial[J/OL]. BMJ，2025，388：e080489[2025-03-07]. https://doi.org/10.1136/bmj-2024-080489.
[18] SOARES B P，CHIEN J D，WINTERMARK M. MR and CT monitoring of recanalization，reperfusion，and penumbra salvage：everything that recanalizes does not necessarily reperfuse[J/OL]. Stroke，2009，40（3 Suppl）：S24-S27[2025-03-09]. https://doi.org/10.1161/STROKEAHA.108.526814.
[19] DESILLES J P，LOYAU S，SYVANNARATH V，et al. Alteplase reduces downstream microvascular thrombosis and improves the benefit of large artery recanalization in stroke[J]. Stroke，2015，46（11）：3241-3248.
[20] DESILLES J P，SYVANNARATH V，DI MEGLIO L，et al. Downstream microvascular thrombosis in cortical venules is an early response to proximal cerebral arterial occlusion[J/OL]. J Am Heart Assoc，2018，7（5）：e007804[2025-03-07]. https://doi.org/10.1161/JAHA.117.007804.
[21] DHOISNE M，PUY L，BRETZNER M，et al. Early reocclusion after successful mechanical thrombectomy for large artery occlusion-related stroke[J]. Int J Stroke，2023，18（6）：712-719.
[22] KAESMACHER J，BOECKH-BEHRENS T，SIMON S，et al. Risk of thrombus fragmentation during endovascular stroke treatment[J]. AJNR Am J Neuroradiol，2017，38（5）：991-998.
[23] ABRAHAM P，SCOTT PANNELL J，SANTIAGO-DIEPPA D R，et al. Vessel wall signal enhancement on 3-T MRI in acute stroke patients after stent retriever thrombectomy[J/OL]. Neurosurg Focus，2017，42（4）：E20[2025-03-07]. https://doi.org/10.3171/2017.1.FOCUS16492.
[24] SANTANA D，LAREDO C，RENÚ A，et al. Incidence and clinico-radiological correlations of early arterial reocclusion after successful thrombectomy in acute ischemic stroke[J]. Transl Stroke Res，2020，11（6）：1314-1321.
[25] SCHÖNFELD M H，KABIRI R，KNIEP H C，et al. Sub-angiographic peripheral emboli in high resolution DWI after endovascular recanalization[J]. J Neurol，2020，267（5）：1401-1406.
[26] WONG G J，YOO B，LIEBESKIND D，et al. Frequency，determinants，and outcomes of emboli to distal and new territories related to mechanical thrombectomy for acute ischemic stroke[J]. Stroke，2021，52（7）：2241-2249.
[27] KAESMACHER J，MEINEL T R，KURMANN C，et al. Safety and efficacy of intra-arterial fibrinolytics as adjunct to mechanical thrombectomy：a systematic review and meta-analysis of observational data[J]. J Neurointerv Surg，2021，13（12）：1073-1080.
[28] 中国卒中学会，中国卒中学会神经介入分会，中华预防医学会卒中预防与控制专业委员会介入学组. 急性缺血性卒中血管内治疗中国指南2023[J]. 中国卒中杂志，2023，18（6）：684-711.
Chinese Stroke Association，Chinese Interventional Neuroradiology Society，Intervention Group of Committee of Stroke Prevention and Control of Chinese Preventive Medicine Association. Chinese guideline for endovascular treatment of acute ischemic stroke 2023[J]. Chin J Stroke，2023，18（6）：684-711.
[29] LIU C，LI F L，SONG J X，et al. POST‐UK（adjunctive intra‐arterial urokinase after successful endovascular thrombectomy in patients with large‐vessel occlusion stroke）：study protocol of a multicenter，prospective，randomized，open‐label，blinded‐end point trial[J/OL]. Stroke：Vascular and Interventional Neurology，2025，5（2）：e001563[2025-04-07]. https://doi.org/10.1161/SVIN.124.001563.
[30] GUO C W，ZI W J，LIU C，et al. Efficacy and safety of intra-arterial thrombolysis following endovascular reperfusion for large-vessel occlusion acute ischemic stroke：an individual patient data meta-analysis of POST-UK and POST-TNK randomized trial[EB/OL].（2025-02-07）[2025-03-01]. https://aha.abstractarchives.com/abstract/isc2025-4202951/efficacy-and-safety-of-intra-arterial-thrombolysis-following-endovascular-reperfusion-for-large-vessel-occlusion-acute-ischemic-stroke-an-individual-patient-data-meta-analysis-of-post-uk-and-post-tnk-randomized-trial.
[31] YANG X G，HE X J，PAN D，et al. Intra-arterial alteplase for acute ischaemic stroke after mechanical thrombectomy（PEARL）：rationale and design of a multicentre，prospective，open-label，blinded-endpoint，randomised controlled trial[J/OL]. BMJ Open，2024，14（11）：e091059[2025-03-07]. https://doi.org/10.1136/bmjopen-2024-091059.
[32] HOU X H，HUANG J C，GUO C W，et al. Safety and efficacy of adjunctive intra-arterial tenecteplase following successful thrombectomy in patients with large vessel occlusion：a phase 1/2 randomized clinical trial[J/OL]. medRxiv，2024[2025-03-07]. https://doi.org/10.1101/2024.11.18.24317521.