TY - JOUR
T1 - Value of intravenous thrombolysis in endovascular treatment for large-vessel anterior circulation stroke
T2 - individual participant data meta-analysis of six randomised trials
AU - Majoie, Charles B.
AU - Cavalcante, Fabiano
AU - IRIS collaborators
AU - Gralla, Jan
AU - Yang, Pengfei
AU - Kaesmacher, Johannes
AU - Treurniet, Kilian M.
AU - Kappelhof, Manon
AU - Yan, Bernard
AU - Suzuki, Kentaro
AU - Zhang, Yongwei
AU - Li, Fengli
AU - Morimoto, Masafumi
AU - Zhang, Lei
AU - Miao, Zhongrong
AU - Rinkel, Leon A.
AU - Huang, Jiacheng
AU - Otsuka, Toshiaki
AU - Wang, Shouchun
AU - Davis, Stephen
AU - Cognard, Christophe
AU - Hong, Bo
AU - Coutinho, Jonathan M.
AU - Song, Jiaxing
AU - Chen, Wenhuo
AU - Emmer, Bart J.
AU - Eker, Omer
AU - Zhang, Liyong
AU - Dobrocky, Tomas
AU - Nguyen, Huy-Thang
AU - Bush, Steven
AU - Peng, Ya
AU - LeCouffe, Natalie E.
AU - Takeuchi, Masataka
AU - Han, Hongxing
AU - Matsumaru, Yuji
AU - Strbian, Daniel
AU - Lingsma, Hester F.
AU - Nieboer, Daan
AU - Yang, Qingwu
AU - Meinel, Thomas
AU - Mitchell, Peter
AU - Kimura, Kazumi
AU - Zi, Wenjie
AU - Nogueira, Raul G.
AU - Liu, Jianmin
AU - Roos, Yvo B.
AU - Majoie, Charles B.
AU - Roos, Yvo B.
AU - Emmer, Bart J.
AU - LeCouffe, Natalie E.
AU - Fischer, Urs
N1 - Funding Information: The IRIS collaboration is funded by an unrestricted grant from Stryker and an institutional grant from the Amsterdam University Medical Centers, University of Amsterdam. We acknowledge all the respective funding sources of each individual trial (ie, DEVT, DIRECT-MT, SKIP, MR CLEAN-NO IV, SWIFT DIRECT, and DIRECT-SAFE) that contributed individual participant data for this study. The authors of the individual trials pooled in this meta-analysis disclosed their funding details in their respective publications. A medical writer reviewed the manuscript before submission (Susan Kaplan). Funding Information: The IRIS collaboration is funded by an unrestricted grant from Stryker and an institutional grant from the Amsterdam University Medical Centers, University of Amsterdam. We acknowledge all the respective funding sources of each individual trial (ie, DEVT, DIRECT-MT, SKIP, MR CLEAN-NO IV, SWIFT DIRECT, and DIRECT-SAFE) that contributed individual participant data for this study. The authors of the individual trials pooled in this meta-analysis disclosed their funding details in their respective publications. A medical writer reviewed the manuscript before submission (Susan Kaplan). Publisher Copyright: © 2023 Elsevier Ltd
PY - 2023/9/16
Y1 - 2023/9/16
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85170673232&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/S0140-6736(23)01142-X
DO - https://doi.org/10.1016/S0140-6736(23)01142-X
M3 - Article
C2 - 37640037
SN - 0140-6736
VL - 402
SP - 965
EP - 974
JO - The Lancet
JF - The Lancet
IS - 10406
ER -