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

中文翻译：

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静脉溶栓在大血管前循环卒中血管内治疗中的价值：六项随机试验的个体参与者数据荟萃分析

建议在血管内治疗前进行静脉溶栓，但对于直接入住有血管内治疗中心的患者，其价值受到质疑。现有的随机对照试验已表明单独血管内治疗的非劣效性或在统计学上尚无结论。我们制定了改善急性缺血性卒中再灌注策略合作，以评估单独血管内治疗与静脉溶栓加血管内治疗的非劣效性。我们进行了系统评价和个体参与者数据荟萃分析，以确定单独血管内治疗与静脉溶栓加血管内治疗相比的非劣效性。我们使用术语“中风”、“血管内治疗”、“静脉溶栓”以及从数据库建立到 2023 年 3 月 9 日发表的文章的同义词搜索了 PubMed 和 MEDLINE。我们纳入了有关感兴趣主题的随机对照试验，没有语言限制。已确定试验的作者同意参加，个体参与者数据由各试验的主要研究人员提供，并由合作者集中整理。我们的主要结果是 90 天的改良 Rankin 量表 (mRS) 评分。单独血管内治疗的非劣效性使用 95% CI 的下限 0·82 围绕调整后的共同比值比 (acOR) 进行评估，以通过序数回归转向改善结果（类似于功能独立性中的 5% 绝对差异） 。我们使用混合效应模型进行所有分析。本研究已在 PROSPERO 注册，CRD42023411986。我们确定了 1081 项研究，其中 6 项研究（n=2313；1153 名参与者随机分配接受单独血管内治疗，1160 名参与者随机分配接受静脉溶栓和血管内治疗）符合分析资格。纳入研究的偏倚风险为低至中等。研究之间的差异很小，主要与溶栓药物的选择和剂量以及执行国家有关。90 天时，单独接受血管内治疗的参与者的中位 mRS 评分为 3 (IQR 1–5)，接受静脉溶栓加血管内治疗的参与者的中位 mRS 评分为 2 (1–4)（acOR 0·89，95% CI 0·76） –1·04)。与静脉溶栓联合血管内治疗相比，单独血管内治疗的颅内出血（0·82、0·68–0·99）发生率较低。有症状的颅内出血和死亡率没有显着差异。对于直接在血管内治疗中心就诊的患者，我们并未确定单独的血管内治疗与静脉溶栓加血管内治疗相比是否具有非劣效性。进一步的研究可以集中于成本效益分析以及当患者特征、药物短缺、或延迟预计会抵消血管内治疗前静脉溶栓的潜在益处。史赛克和阿姆斯特丹大学医学中心、阿姆斯特丹大学。