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Meta-Analysis
. 2023 Sep 16;402(10406):965-974.
doi: 10.1016/S0140-6736(23)01142-X. Epub 2023 Aug 25.

Value of intravenous thrombolysis in endovascular treatment for large-vessel anterior circulation stroke: individual participant data meta-analysis of six randomised trials

Charles B Majoie  1 , Fabiano Cavalcante  2 , Jan Gralla  3 , Pengfei Yang  4 , Johannes Kaesmacher  3 , Kilian M Treurniet  5 , Manon Kappelhof  2 , Bernard Yan  6 , Kentaro Suzuki  7 , Yongwei Zhang  8 , Fengli Li  9 , Masafumi Morimoto  10 , Lei Zhang  8 , Zhongrong Miao  11 , Leon A Rinkel  12 , Jiacheng Huang  9 , Toshiaki Otsuka  13 , Shouchun Wang  14 , Stephen Davis  6 , Christophe Cognard  15 , Bo Hong  16 , Jonathan M Coutinho  12 , Jiaxing Song  9 , Wenhuo Chen  17 , Bart J Emmer  2 , Omer Eker  18 , Liyong Zhang  19 , Tomas Dobrocky  3 , Huy-Thang Nguyen  20 , Steven Bush  21 , Ya Peng  22 , Natalie E LeCouffe  12 , Masataka Takeuchi  23 , Hongxing Han  24 , Yuji Matsumaru  25 , Daniel Strbian  26 , Hester F Lingsma  27 , Daan Nieboer  27 , Qingwu Yang  9 , Thomas Meinel  28 , Peter Mitchell  21 , Kazumi Kimura  7 , Wenjie Zi  9 , Raul G Nogueira  29 , Jianmin Liu  4 , Yvo B Roos  12 , Urs Fischer  30 ; IRIS collaborators
Collaborators, Affiliations
Meta-Analysis

Value of intravenous thrombolysis in endovascular treatment for large-vessel anterior circulation stroke: individual participant data meta-analysis of six randomised trials

Charles B Majoie et al. Lancet. .

Abstract

Background: Intravenous thrombolysis is recommended before endovascular treatment, but its value has been questioned in patients who are admitted directly to centres capable of endovascular treatment. Existing randomised controlled trials have indicated non-inferiority of endovascular treatment alone or have been statistically inconclusive. We formed the Improving Reperfusion Strategies in Acute Ischaemic Stroke collaboration to assess non-inferiority of endovascular treatment alone versus intravenous thrombolysis plus endovascular treatment.

Methods: We conducted a systematic review and individual participant data meta-analysis to establish non-inferiority of endovascular treatment alone versus intravenous thrombolysis plus endovascular treatment. We searched PubMed and MEDLINE with the terms "stroke", "endovascular treatment", "intravenous thrombolysis", and synonyms for articles published from database inception to March 9, 2023. We included randomised controlled trials on the topic of interest, without language restrictions. Authors of the identified trials agreed to take part, and individual participant data were provided by the principal investigators of the respective trials and collated centrally by the collaborators. Our primary outcome was the 90-day modified Rankin Scale (mRS) score. Non-inferiority of endovascular treatment alone was assessed using a lower boundary of 0·82 for the 95% CI around the adjusted common odds ratio (acOR) for shift towards improved outcome (analogous to 5% absolute difference in functional independence) with ordinal regression. We used mixed-effects models for all analyses. This study is registered with PROSPERO, CRD42023411986.

Findings: We identified 1081 studies, and six studies (n=2313; 1153 participants randomly assigned to receive endovascular treatment alone and 1160 randomly assigned to receive intravenous thrombolysis and endovascular treatment) were eligible for analysis. The risk of bias of the included studies was low to moderate. Variability between studies was small, and mainly related to the choice and dose of the thrombolytic drug and country of execution. The median mRS score at 90 days was 3 (IQR 1-5) for participants who received endovascular treatment alone and 2 (1-4) for participants who received intravenous thrombolysis plus endovascular treatment (acOR 0·89, 95% CI 0·76-1·04). Any intracranial haemorrhage (0·82, 0·68-0·99) occurred less frequently with endovascular treatment alone than with intravenous thrombolysis plus endovascular treatment. Symptomatic intracranial haemorrhage and mortality rates did not differ significantly.

Interpretation: We did not establish non-inferiority of endovascular treatment alone compared with intravenous thrombolysis plus endovascular treatment in patients presenting directly at endovascular treatment centres. Further research could focus on cost-effectiveness analysis and on individualised decisions when patient characteristics, medication shortages, or delays are expected to offset a potential benefit of administering intravenous thrombolysis before endovascular treatment.

Funding: Stryker and Amsterdam University Medical Centers, University of Amsterdam.

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Conflict of interest statement

Declaration of interests CBM reports grants from CardioVasculair Onderzoek Nederland by the Dutch Heart Foundation, TWIN Foundation, the European Commission, Healthcare Evaluation Netherlands, and Stryker (all paid to institution); and is a minority interest shareholder of Nicolab. YBR reports being a minor shareholder of Nicolab. JG reports consultancy funds from Medtronic as Global Principal Investigator of STAR (NCT01327989) and Swift Direct (NCT03192332) and from Cerenovus (now part of Johnson & Johnson) and participation on a data safety monitoring board or advisory board (clinical ethics committee member of the Promise Study) for Penumbra. CC reports consulting fees from Microvention, Medtronic, Cerenovus, MIVI, and Stryker. TD reports payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from Microvention. BJE reports institutional funding from HealthHolland Top Sector Life Sciences and Nicolab. RGN reports funding from Cerenovus as Principal Investigator of the ENDOLOW trial and from Stryker Neurovascular as Principal Investigator of the DUSK trial; consulting fees for advisory roles with Anaconda, Biogen, Cerenovus, Genentech, Philips, Hybernia, Imperative Care, Medtronic, Phenox, Philips, Prolong Pharmaceuticals, Stryker Neurovascular, Shanghai Wallaby, and Synchron; stock options for advisory roles with Astrocyte, Brainomix, Cerebrotech, Ceretrieve, Corindus Vascular Robotics, Vesalio, Viz-AI, RapidPulse, and Perfuze; and being an investor in Viz-AI, Perfuze, Cerebrotech, Reist–Q’Apel Medical, Truvic, Vastrax, and Viseon. UF reports funding from Medtronic, Stryker, Rapid Medical, Phenox, Penumbra, Swiss National Science Foundation, CSL Behring, Portola (now part of Alexion), Boehringer Ingelheim, and Biogen. SD reports institutional funding from the National Health and Medical Research Council and funding from Medtronic, Abbott, and CSL Behring for participation on data safety monitoring boards or advisory boards. PM reports institutional funding from Stryker and Medtronic. BY reports institutional research grants from Stryker and Medtronic. All other authors declare no competing interests.

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