Time to Treatment With Intravenous Thrombolysis Before Thrombectomy and Functional Outcomes in Acute Ischemic Stroke
Authors: Kaesmacher Johannes , Cavalcante Fabiano , Kappelhof Manon , Treurniet Kilian M. , Rinkel Leon , Liu Jianmin , Yan Bernard , Zi Wenjie , Kimura Kazumi , Eker Omer F. , Zhang Yongwei , Piechowiak Eike I. , van Zwam Wim , Liu Sheng , Strbian Daniel , Uyttenboogaart Maarten , Dobrocky Tomas , Miao Zhongrong , Suzuki Kentaro , Zhang Lei , van Oostenbrugge Robert , Meinel Thomas R. , Guo Changwei , Seiffge David , Yin Congguo , Bütikofer Lukas , Lingsma Hester , Nieboer Daan , Yang Pengfei , Mitchell Peter , Majoie Charles , Fischer Urs , Roos Yvo , Gralla Jan ,   IRIS Collaborators, Nogueira Raul , Yang Qingwu , Matsumaru Yuji , Bush Steven , Li Fengli , Huang Jiacheng , Song Jiaxing , Hong Bo , Chen Wenhuo , Peng Ya , Han Hongxing , Zhang Liyong , Wang Shouchun , Fang Qi , Xu Chenghua , Zhang Yongxin , Li Zifu , Xing Pengfei , Shen Hongjian , Zhang Ping , Zhang Xiaoxi , Davis Stephen , Nguyen Huy-Thang , Donnan Geoffrey , Huo Xiaochuan , Nan Guangxian , Bivard Andrew , Ma Henry , Luu Vu Dang , Campbell Bruce , Emmer Bart J , Coutinho Jonathan M , LeCouffe Natalie E , Dippel Diederik W J , Lugt Aad van der , Costalat Vincent , Lycklama Geert , Hofmeijer Jeannette , Norden Anouk van , Otsuka Toshiaki , Takeuchi Masataka , Morimoto Masafumi , Kanazawa Ryuzaburo , Takayama Yohei , Kamiya Yuki , Shigeta Keigo , Okubo Seiji , Hayakawa Mikito , Cognard Christophe , Jung Simon , Gaultier Marnat , Sibon Igor , Bourcier Romain , Gaalon Solene de , Papagiannaki Chrysanthi , Lefebvre Margaux , Liebeskind David S 
Published: February 2024

ImportanceThe benefit of intravenous thrombolysis (IVT) for acute ischemic stroke declines with longer time from symptom onset, but it is not known whether a similar time dependency exists for IVT followed by thrombectomy.ObjectiveTo determine whether the benefit associated with IVT plus thrombectomy vs thrombectomy alone decreases with treatment time from symptom onset.Design, Setting, and ParticipantsIndividual participant data meta-analysis from 6 randomized clinical trials comparing IVT plus thrombectomy vs thrombectomy alone. Enrollment was between January 2017 and July 2021 at 190 sites in 15 countries. All participants were eligible for IVT and thrombectomy and presented directly at thrombectomy-capable stroke centers (n = 2334). For this meta-analysis, only patients with an anterior circulation large-vessel occlusion were included (n = 2313).ExposureInterval from stroke symptom onset to expected administration of IVT and treatment with IVT plus thrombectomy vs thrombectomy alone.Main Outcomes and MeasuresThe primary outcome analysis tested whether the association between the allocated treatment (IVT plus thrombectomy vs thrombectomy alone) and disability at 90 days (7-level modified Rankin Scale [mRS] score range, 0 [no symptoms] to 6 [death]; minimal clinically important difference for the rates of mRS scores of 0-2: 1.3%) varied with times from symptom onset to expected administration of IVT.ResultsIn 2313 participants (1160 in IVT plus thrombectomy group vs 1153 in thrombectomy alone group; median age, 71 [IQR, 62 to 78] years; 44.3% were female), the median time from symptom onset to expected administration of IVT was 2 hours 28 minutes (IQR, 1 hour 46 minutes to 3 hours 17 minutes). There was a statistically significant interaction between the time from symptom onset to expected administration of IVT and the association of allocated treatment with functional outcomes (ratio of adjusted common odds ratio [OR] per 1-hour delay, 0.84 [95% CI, 0.72 to 0.97], P = .02 for interaction). The benefit of IVT plus thrombectomy decreased with longer times from symptom onset to expected administration of IVT (adjusted common OR for a 1-step mRS score shift toward improvement, 1.49 [95% CI, 1.13 to 1.96] at 1 hour, 1.25 [95% CI, 1.04 to 1.49] at 2 hours, and 1.04 [95% CI, 0.88 to 1.23] at 3 hours). For a mRS score of 0, 1, or 2, the predicted absolute risk difference was 9% (95% CI, 3% to 16%) at 1 hour, 5% (95% CI, 1% to 9%) at 2 hours, and 1% (95% CI, −3% to 5%) at 3 hours. After 2 hours 20 minutes, the benefit associated with IVT plus thrombectomy was not statistically significant and the point estimate crossed the null association at 3 hours 14 minutes.Conclusions and RelevanceIn patients presenting at thrombectomy-capable stroke centers, the benefit associated with IVT plus thrombectomy vs thrombectomy alone was time dependent and statistically significant only if the time from symptom onset to expected administration of IVT was short.