@article {Meinelneurintsurg-2022-019207, author = {Thomas R Meinel and Johannes Kaesmacher and Lukas Buetikofer and Daniel Strbian and Omer Faruk Eker and Christophe Cognard and Pasquale Mordasini and Sandro Deppeler and Vitor Mendes Pereira and Jean Fran{\c c}ois Albucher and Jean Darcourt and Romain Bourcier and Benoit Guillon and Chrysanthi Papagiannaki and Guillaume Costentin and Gerli Sibolt and Silja R{\"a}ty and Benjamin Gory and S{\'e}bastien Richard and Jan Liman and Marielle Ernst and Marion Boulanger and Charlotte Barbier and Laura Mechtouff and Liqun Zhang and Gaultier Marnat and Igor Sibon and Omid Nikoubashman and Arno Reich and Arturo Consoli and David Weisenburger and Manuel Requena and Alvaro Garcia-Tornel and Suzana Saleme and Sol{\`e}ne Moulin and Paolo Pagano and Guillaume Saliou and Emmanuel Carrera and Kevin Janot and Marti Boix and Raoul Pop and Lucie Della Schiava and Andreas Luft and Michel Piotin and Jean Christophe Gentric and Aleksandra Pikula and Waltraud Pfeilschifter and Marcel Arnold and Adnan Siddiqui and Michael T Froehler and Anthony J Furlan and Ren{\'e} Chapot and Martin Wiesmann and Paolo Machi and Hans-Christoph Diener and Zsolt Kulcsar and Leo Bonati and Claudio Bassetti and Simon Escalard and David Liebeskind and Jeffrey L Saver and Urs Fischer and Jan Gralla}, editor = {,}, title = {Time to treatment with bridging intravenous alteplase before endovascular treatment:subanalysis of the randomized controlled SWIFT-DIRECT trial}, elocation-id = {neurintsurg-2022-019207}, year = {2022}, doi = {10.1136/jnis-2022-019207}, publisher = {British Medical Journal Publishing Group}, abstract = {Background We hypothesized that treatment delays might be an effect modifier regarding risks and benefits of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT).Methods We used the dataset of the SWIFT-DIRECT trial, which randomized 408 patients to IVT+MT or MT alone. Potential interactions between assignment to IVT+MT and expected time from onset-to-needle (OTN) as well as expected time from door-to-needle (DTN) were included in regression models. The primary outcome was functional independence (modified Rankin Scale (mRS) 0{\textendash}2) at 3 months. Secondary outcomes included mRS shift, mortality, recanalization rates, and (symptomatic) intracranial hemorrhage at 24 hours.Results We included 408 patients (IVT+MT 207, MT 201, median age 72 years (IQR 64{\textendash}81), 209 (51.2\%) female). The expected median OTN and DTN were 142 min and 54 min in the IVT+MT group and 129 min and 51 min in the MT alone group. Overall, there was no significant interaction between OTN and bridging IVT assignment regarding either the functional (adjusted OR (aOR) 0.76, 95\% CI 0.45 to 1.30) and safety outcomes or the recanalization rates. Analysis of in-hospital delays showed no significant interaction between DTN and bridging IVT assignment regarding the dichotomized functional outcome (aOR 0.48, 95\% CI 0.14 to 1.62), but the shift and mortality analyses suggested a greater benefit of IVT when in-hospital delays were short.Conclusions We found no evidence that the effect of bridging IVT on functional independence is modified by overall or in-hospital treatment delays. Considering its low power, this subgroup analysis could have missed a clinically important effect, and exploratory analysis of secondary clinical outcomes indicated a potentially favorable effect of IVT with shorter in-hospital delays. Heterogeneity of the IVT effect size before MT should be further analyzed in individual patient meta-analysis of comparable trials.Trial registration number URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03192332Data are available upon reasonable request. De-identified data, together with a data dictionary, will be made accessible after ethics clearance and upon submission of a reasonable request with a research plan to the corresponding author.}, issn = {1759-8478}, URL = {https://jnis.bmj.com/content/early/2022/07/28/jnis-2022-019207}, eprint = {https://jnis.bmj.com/content/early/2022/07/28/jnis-2022-019207.full.pdf}, journal = {Journal of NeuroInterventional Surgery} }