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Meta-Analysis
. 2025 Oct 1;82(10):1031-1039.
doi: 10.1001/jamaneurol.2025.2610.

Intracranial Hemorrhage in Patients With Stroke After Endovascular Treatment With or Without IV Alteplase: An Individual Participant Data Meta-Analysis

Yu Zhou  1   2 , Lei Zhang  1 , Fabiano Cavalcante  3 , Kentaro Suzuki  4 , Kilian M Treurniet  3   5   6 , Bernard Yan  7 , Peter Mitchell  8 , Steven Bush  8 , Urs Fischer  9 , Johannes Kaesmacher  10 , Jan Gralla  10 , Daniel Strbian  11 , Roman Rohner  10   12 , Manon Kappelhof  3 , Yvo Roos  13 , Charles Majoie  3 , Wenjie Zi  14 , Qingwu Yang  14 , Yongwei Zhang  1   2 , Yuji Matsumaru  15 , Kazumi Kimura  4 , Xiaofei Ye  16 , Pengfei Yang  1   2 , Jianmin Liu  1   2 ; IRIS collaborators
Collaborators, Affiliations
Meta-Analysis

Intracranial Hemorrhage in Patients With Stroke After Endovascular Treatment With or Without IV Alteplase: An Individual Participant Data Meta-Analysis

Yu Zhou et al. JAMA Neurol. .

Abstract

Importance: For patients with acute ischemic stroke due to anterior circulation large vessel occlusion and presenting directly to endovascular treatment (EVT)-capable centers, intravenous thrombolysis (IVT) before EVT raises concerns about intracranial hemorrhage (ICH), but details are not well understood.

Objective: To determine the frequency and subtypes of ICH in patients treated with IVT plus EVT vs EVT alone and to determine the association between various ICH subtypes and patient functional outcomes.

Data sources: PubMed and MEDLINE were searched from database inception through March 9, 2023.

Study selection: Randomized clinical trials comparing EVT alone with IVT plus EVT for anterior circulation large vessel occlusion stroke were included.

Data extraction and synthesis: Individual participant data were extracted following the Preferred Reporting Items for Systematic Review and Meta-Analyses of independent participant data (PRISMA-IPD) reporting guidelines. Data were pooled using a random-effects model. Data were analyzed between April 2024 and February 2025.

Main outcomes and measures: The primary outcomes were ICH and its subtypes according to the Heidelberg Bleeding Classification (hemorrhagic infarction type 1 [HI1], hemorrhagic infarction type 2 [HI2], parenchymal hematoma type 1 [PH1], parenchymal hematoma type 2 [PH2], and others; symptomatic or asymptomatic ICH), which were evaluated using a mixed-model approach with multinomial or binary regression.

Results: The analysis involved 2313 participants (1160 allocated to the IVT plus EVT group vs 1153 to EVT alone; median [IQR] age, 71 [62-78] years; 1025 female participants [44%]) from 6 studies. Any ICH occurred in 768 of 2261 participants (34%). IVT was associated with an increased rate of any ICH (411 of 1133 [36%] vs 357 of 1128 [32%]; adjusted odds ratio [OR], 1.23; 95% CI, 1.02-1.49; P = .03) and a higher rate of any parenchymal hematoma (PH1 or PH2) (82 of 1133 [7%] vs 61 of 1128 [5%]; adjusted OR, 1.54; 95% CI, 1.02-2.34; P = .04). Compared with participants without ICH, asymptomatic ICH (adjusted common OR, 0.55; 95% CI, 0.46-0.65) and symptomatic ICH (adjusted common OR, 0.08; 95% CI, 0.05-0.13) were both associated with worse functional outcomes, and there was a graded association of ICH radiologic patterns and patient outcomes.

Conclusions and relevance: In this individual participant data meta-analysis, compared with EVT alone, IVT plus EVT modestly increased the risk of ICH, notably any parenchymal hematoma. Although ICH was associated with worse functional outcomes, this effect may be offset by IVT's benefit in final successful reperfusion and early reperfusion.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Cavalcante reported grants from Boehringer Ingelheim, the Dutch Brain Foundation, the Dutch Heart Foundation, and Stryker during the conduct of the study. Dr Fischer reported research support from Medtronic; grants from Penumbra, Phenox DISTAL, Rapid Medical, Stryker, the Swiss Heart Foundation, and the Swiss National Science Foundation; serving as principal investigator (PI) of the ELAN trail; serving as co-PI of the DISTAL, TECNO, SWIFT DIRECT, SWITCH, ELAPSE, and ICARUS trials during the conduct of the study; consultant fees paid to institution from AbbVie, AstraZeneca (formerly Alexion/Portola), Bayer, Biogen, Boehringer Ingelheim, CSL, and Siemens outside the submitted work; and serving as President of the European Stroke Organization and Schweizerische Neurologische Gesellschaft and as President-Elect of the Swiss Federation of Clinical Neuro-Societies. Dr Kaesmacher reported grants from Boehringer Ingelheim (IRIS, TECNO) and the Swiss National Science Foundation (TECNO) during the conduct of the study and grants from the Bangerter Foundation, Siemens, and the Swiss Heart Foundation outside the submitted work. Dr Gralla reported consultancy grants from Medtronic for serving as global co-PI of the SWIFT DIRECT trial and consultancy fees from Johnson & Johnson outside the submitted work. Dr Rohner reported grants from the Department of Teaching and Research, Insel Gruppe AG, the Gottfried and Julia Bangerter-Rhyner-Foundation, and the Swiss Heart Foundation outside the submitted work. Dr Roos reported being a minor shareholder in Nicolab outside the submitted work. Dr Majoie reported grants paid to institution from Boehringer Ingelheim, CVON-Dutch Heart Foundation, and Stryker during the conduct of the study; grants paid to institution from the European Union outside the submitted work; and being a minority interest shareholder in Nicolab. Dr Matsumaru reported personal fees from Medtronic, Stryker, and Terumo outside the submitted work. No other disclosures were reported.

References

    1. Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2019;50(12):e344-e418. doi: 10.1161/STR.0000000000000211 - DOI - PubMed
    1. Bellwald S, Weber R, Dobrocky T, et al. Direct mechanical intervention versus bridging therapy in stroke patients eligible for intravenous thrombolysis: a pooled analysis of 2 registries. Stroke. 2017;48(12):3282-3288. doi: 10.1161/STROKEAHA.117.018459 - DOI - PubMed
    1. Mitchell PJ, Yan B, Churilov L, et al. ; DIRECT-SAFE Investigators . Endovascular thrombectomy versus standard bridging thrombolytic with endovascular thrombectomy within 4·5 h of stroke onset: an open-label, blinded-endpoint, randomised non-inferiority trial. Lancet. 2022;400(10346):116-125. doi: 10.1016/S0140-6736(22)00564-5 - DOI - PubMed
    1. Fischer U, Kaesmacher J, Strbian D, et al. ; SWIFT DIRECT Collaborators . Thrombectomy alone versus intravenous alteplase plus thrombectomy in patients with stroke: an open-label, blinded-outcome, randomised non-inferiority trial. Lancet. 2022;400(10346):104-115. doi: 10.1016/S0140-6736(22)00537-2 - DOI - PubMed
    1. Zi W, Qiu Z, Li F, et al. ; DEVT Trial Investigators . Effect of endovascular treatment alone vs intravenous alteplase plus endovascular treatment on functional independence in patients with acute ischemic stroke: the DEVT randomized clinical trial. JAMA. 2021;325(3):234-243. doi: 10.1001/jama.2020.23523 - DOI - PMC - PubMed

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