Time to treatment with bridging intravenous alteplase before endovascular treatment:subanalysis of the randomized controlled SWIFT-DIRECT trial
Authors: Meinel Thomas R , Kaesmacher Johannes , Buetikofer Lukas , Strbian Daniel , Eker Omer Faruk , Cognard Christophe , Mordasini Pasquale , Deppeler Sandro , Mendes Pereira Vitor , Albucher Jean François , Darcourt Jean , Bourcier Romain , Guillon Benoit , Papagiannaki Chrysanthi , Costentin Guillaume , Sibolt Gerli , Räty Silja , Gory Benjamin , Richard Sébastien , Liman Jan , Ernst Marielle , Boulanger Marion , Barbier Charlotte , Mechtouff Laura , Zhang Liqun , Marnat Gaultier , Sibon Igor , Nikoubashman Omid , Reich Arno , Consoli Arturo , Weisenburger David , Requena Manuel , Garcia-Tornel Alvaro , Saleme Suzana , Moulin Solène , Pagano Paolo , Saliou Guillaume , Carrera Emmanuel , Janot Kevin , Boix Marti , Pop Raoul , Della Schiava Lucie , Luft Andreas , Piotin Michel , Gentric Jean Christophe , Pikula Aleksandra , Pfeilschifter Waltraud , Arnold Marcel , Siddiqui Adnan , Froehler Michael T , Furlan Anthony J , Chapot René , Wiesmann Martin , Machi Paolo , Diener Hans-Christoph , Kulcsar Zsolt , Bonati Leo , Bassetti Claudio , Escalard Simon , Liebeskind David , Saver Jeffrey L , Fischer Urs , Gralla Jan 
Published: July 2022

BackgroundWe hypothesized that treatment delays might be an effect modifier regarding risks and benefits of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT).MethodsWe 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.ResultsWe 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.ConclusionsWe 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 numberURL:https://www.clinicaltrials.gov; Unique identifier:NCT03192332