TY - JOUR T1 - Time to treatment with bridging intravenous alteplase before endovascular treatment:subanalysis of the randomized controlled SWIFT-DIRECT trial JF - Journal of NeuroInterventional Surgery JO - J NeuroIntervent Surg DO - 10.1136/jnis-2022-019207 SP - neurintsurg-2022-019207 AU - Thomas R Meinel AU - Johannes Kaesmacher AU - Lukas Buetikofer AU - Daniel Strbian AU - Omer Faruk Eker AU - Christophe Cognard AU - Pasquale Mordasini AU - Sandro Deppeler AU - Vitor Mendes Pereira AU - Jean François Albucher AU - Jean Darcourt AU - Romain Bourcier AU - Benoit Guillon AU - Chrysanthi Papagiannaki AU - Guillaume Costentin AU - Gerli Sibolt AU - Silja Räty AU - Benjamin Gory AU - Sébastien Richard AU - Jan Liman AU - Marielle Ernst AU - Marion Boulanger AU - Charlotte Barbier AU - Laura Mechtouff AU - Liqun Zhang AU - Gaultier Marnat AU - Igor Sibon AU - Omid Nikoubashman AU - Arno Reich AU - Arturo Consoli AU - David Weisenburger AU - Manuel Requena AU - Alvaro Garcia-Tornel AU - Suzana Saleme AU - Solène Moulin AU - Paolo Pagano AU - Guillaume Saliou AU - Emmanuel Carrera AU - Kevin Janot AU - Marti Boix AU - Raoul Pop AU - Lucie Della Schiava AU - Andreas Luft AU - Michel Piotin AU - Jean Christophe Gentric AU - Aleksandra Pikula AU - Waltraud Pfeilschifter AU - Marcel Arnold AU - Adnan Siddiqui AU - Michael T Froehler AU - Anthony J Furlan AU - René Chapot AU - Martin Wiesmann AU - Paolo Machi AU - Hans-Christoph Diener AU - Zsolt Kulcsar AU - Leo Bonati AU - Claudio Bassetti AU - Simon Escalard AU - David Liebeskind AU - Jeffrey L Saver AU - Urs Fischer AU - Jan Gralla A2 - , Y1 - 2022/07/28 UR - http://jnis.bmj.com/content/early/2022/07/28/jnis-2022-019207.abstract N2 - 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) 0–2) 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 64–81), 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. ER -