Time to treatment with bridging intravenous alteplase before endovascular treatment: subanalysis of the randomized controlled SWIFT-DIRECT trial
Por:
Meinel, TR, Kaesmacher, J, Buetikofer, L, Strbian, D, Eker, OF, Cognard, C, Mordasini, P, Deppeler, S, Pereira, VM, Albucher, JF, Darcourt, J, Bourcier, R, Guillon, B, Papagiannaki, C, Costentin, G, Sibolt, G, Raty, S, Gory, B, Richard, S, Liman, J, Ernst, M, Boulanger, M, Barbier, C, Mechtouff, L, Zhang, LQ, Marnat, G, Sibon, I, Nikoubashman, O, Reich, A, Consoli, A, Weisenburger, D, Requena, M, Garcia-Tornel, A, Saleme, S, Moulin, S, Pagano, P, Saliou, G, Carrera, E, Janot, K, Boix, M, Pop, R, Della Schiava, L, Luft, A, Piotin, M, Gentric, JC, Pikula, A, Pfeilschifter, W, Arnold, M, Siddiqui, A, Froehler, MT, Furlan, AJ, Chapot, R, Wiesmann, M, Machi, P, Diener, HC, Kulcsar, Z, Bonati, L, Bassetti, C, Escalard, S, Liebeskind, D, Saver, JL, Fischer, U and Gralla, J
Ahead of Print:
1 jul 2022
Resumen:
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.
Filiaciones:
Meinel, TR:
Bern Univ Hosp, Dept Neurol, Inselspital, Bern, Switzerland
Univ Bern, Bern, Switzerland
Kaesmacher, J:
Univ Bern, Bern, Switzerland
Bern Univ Hosp, Univ Inst Diagnost & Intervent Neuroradiol, Inselspital, Bern, Switzerland
Buetikofer, L:
Univ Bern, CTU Bern, Bern, Switzerland
Strbian, D:
Helsinki Univ Hosp, Dept Neurol, Helsinki, Finland
Univ Helsinki, Helsinki, Finland
Eker, OF:
Hosp Civils Lyon, Dept Neuroradiol, Lyon, France
Cognard, C:
Ctr Hosp Univ Toulouse, Dept Diagnost & Therapeut Neuroradiol, Toulouse, France
Mordasini, P:
Univ Bern, Bern, Switzerland
Bern Univ Hosp, Univ Inst Diagnost & Intervent Neuroradiol, Inselspital, Bern, Switzerland
Deppeler, S:
Univ Bern, Bern, Switzerland
Bern Univ Hosp, Dept Neurol, Neuro Clin Trial Unit, Inselspital, Bern, Switzerland
Pereira, VM:
Univ Toronto, Univ Hlth Network, Toronto Western Hosp, Dept Med Imaging,Div Neuroradiol, Toronto, ON, Canada
Univ Hlth Network, Univ Toronto, Toronto Western Hosp, Dept Surg,Div Neuroradiol, Toronto, ON, Canada
Univ Toronto, Univ Hlth Network, Dept Med Imaging, Div Neurosurg,Toronto Western Hosp, Toronto, ON, Canada
Univ Toronto, Univ Hlth Network, Toronto Western Hosp, Dept Surg,Div Neurosurg, Toronto, ON, Canada
Albucher, JF:
Ctr Hosp Univ Toulouse, Dept Neurol, Toulouse, France
Darcourt, J:
Hosp Civils Lyon, Dept Neuroradiol, Lyon, France
Bourcier, R:
Nantes Univ, Dept Diagnost & Intervent Neuroradiol, Ctr Hosp Univ Nantes, Nantes, France
Guillon, B:
Nantes Univ, Dept Neurol, Ctr Hosp Univ Nantes, Nantes, France
Papagiannaki, C:
CHU Rouen, Dept Radiol, Rouen, France
Costentin, G:
CHU Rouen, Dept Neurol, Rouen, France
Sibolt, G:
Helsinki Univ Hosp, Dept Neurol, Helsinki, Finland
Univ Helsinki, Helsinki, Finland
Raty, S:
Helsinki Univ Hosp, Dept Neurol, Helsinki, Finland
Univ Helsinki, Helsinki, Finland
Gory, B:
Univ Lorraine, INSERM U1254, Dept Diagnost & Therapeut Neuroradiol, CHRU Nancy, Nancy, France
Richard, S:
Univ Lorraine, Stroke Unit, INSERM U1116, Dept Neurol,CHRU Nancy, Nancy, France
Liman, J:
Klinikum Nurnberg, Dept Neurol, Nurnberg, Germany
Ernst, M:
Univ Med Ctr Gottingen, Dept Diagnost & Intervent Neuroradiol, Gottingen, Germany
Boulanger, M:
Univ Caen Normandie, Deparment Neurol, INSERM U1237, CHU Caen Normandie, Caen, France
Barbier, C:
Univ Caen Normandie, Dept Neuroradiol, INSERM U1237, CHU Caen Normandie, Caen, France
Mechtouff, L:
Hosp Civils Lyon, Dept Vasc Neurol, Lyon, France
Zhang, LQ:
St Georges Univ Hosp NHS Fdn Trust, Dept Neurol, London, England
Marnat, G:
Univ Bordeaux, Dept Intervent & Diagnost Neuroradiol, CHU Bordeaux, Bordeaux, France
Sibon, I:
Univ Bordeaux, Stroke Unit, CHU Bordeaux, Bordeaux, France
Nikoubashman, O:
Univ Hosp RWTH Aachen, Dept Neuroradiol, Aachen, Germany
Reich, A:
Univ Hosp RWTH Aachen, Dept Neurol, Aachen, Germany
Consoli, A:
Foch Hosp, Dept Stroke & Diagnost & Intervent Neuroradiol, Suresnes, France
Weisenburger, D:
Foch Hosp, Dept Stroke & Diagnost & Intervent Neuroradiol, Suresnes, France
Requena, M:
Hosp Vall dHeborn, Dept Neurol, Stroke Unit, Barcelona, Spain
Hosp Vall dHeborn, Dept Radiol, Intervent Neuroradiol, Barcelona, Spain
Garcia-Tornel, A:
Hosp Vall dHeborn, Dept Neurol, Stroke Unit, Barcelona, Spain
Saleme, S:
CHU Limoges, Dept Neuroradiol, Limoges, France
Moulin, S:
CHU Reims, Dept Neurol, Reims, France
Pagano, P:
CHU Reims, Dept Neuroradiol, Reims, France
Saliou, G:
CHU Vaudois, Serv Intervent & Diagnost Radiol, Lausanne, Switzerland
Univ Lausanne, Lausanne, Switzerland
Carrera, E:
Hop Univ Geneve, Dept Neurol, Geneva, Switzerland
Janot, K:
Tours Univ Hosp, Dept Diagnost & Intervent Neuroradiol, Tours, France
:
Univ Hosp Germans Trias i Pujol, Dept Neurosci, Stroke Unit, Barcelona, Spain
Pop, R:
Strasbourg Univ Hosp, Dept Intervent Neuroradiol, Strasbourg, France
Della Schiava, L:
Lille Univ Hosp, Dept Neurol, Lille, France
Luft, A:
Univ Hosp Zurich, Dept Neurol, Zurich, Switzerland
Ctr Neurol & Rehabil, Dept Neurol, Cereneo, Vitznau, Switzerland
Piotin, M:
Fdn Rothschild Hosp, Dept Intervent Neuroradiol, Paris, France
Gentric, JC:
Brest Univ Hosp, Dept Neuroradiol, Brest, France
Pikula, A:
Univ Toronto, Univ Hlth Network, Toronto Western Hosp, Dept Neurol, Toronto, ON, Canada
Pfeilschifter, W:
Univ Hosp Frankfurt, Dept Neurol, Frankfurt, Germany
Arnold, M:
Bern Univ Hosp, Dept Neurol, Inselspital, Bern, Switzerland
Univ Bern, Bern, Switzerland
Siddiqui, A:
Univ Buffalo, Jacobs Sch Med & Biomed Sci, Dept Neurosurg, Buffalo, NY USA
Froehler, MT:
Vanderbilt Univ Sch Med, Vanderbilt Cerebrovasc Program, Nashville, TN USA
Furlan, AJ:
Case Western Reserve Univ, Sch Med, Cleveland, OH USA
Chapot, R:
Alfried Krupp Hosp, Dept Intracranial Endovasc Therapy, Essen, Germany
Wiesmann, M:
Univ Hosp RWTH Aachen, Dept Neuroradiol, Aachen, Germany
Machi, P:
Hop Univ Geneve, Dept Neuroradiol, Geneva, Switzerland
Diener, HC:
Inst Med Informat Biometry & Epidemiol IMIBE, Dept Neuroepidemiol, Essen, Germany
Kulcsar, Z:
Univ Hosp Zurich, Dept Neuroradiol, Zurich, Switzerland
Bonati, L:
Univ Hosp Basel, Dept Neurol, Basel, Switzerland
Bassetti, C:
Bern Univ Hosp, Dept Neurol, Inselspital, Bern, Switzerland
Univ Bern, Bern, Switzerland
Escalard, S:
Fdn Rothschild Hosp, Dept Intervent Neuroradiol, Paris, France
Liebeskind, D:
Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA
Univ Calif Los Angeles, David Geffen Sch Med, Comprehens Stroke Ctr, Los Angeles, CA 90095 USA
Saver, JL:
Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA
Univ Calif Los Angeles, David Geffen Sch Med, Comprehens Stroke Ctr, Los Angeles, CA 90095 USA
Fischer, U:
Bern Univ Hosp, Dept Neurol, Inselspital, Bern, Switzerland
Univ Bern, Bern, Switzerland
Univ Hosp Basel, Dept Neurol, Basel, Switzerland
Gralla, J:
Univ Bern, Bern, Switzerland
Bern Univ Hosp, Univ Inst Diagnost & Intervent Neuroradiol, Inselspital, Bern, Switzerland
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