Background The benefit of intravenous thrombolysis is time dependent. It remains unclear, however, whether dramatic shortening of door-to-needle time (DNT) among different types of hospitals nationwide does not compromise safety and still improves outcome. Methods and Results Multifaceted intervention to shorten DNT was introduced at a national level, and prospectively collected data from a registry between 2004 and 2019 were analyzed. Generalized estimating equation was used to identify the association between DNT and outcomes independently from prespecified baseline variables. The primary outcome was modified Rankin score 0 to 1 at 3 months, and secondary outcomes were parenchymal hemorrhage/intracerebral hemorrhage (ICH), any ICH, and death. Of 31 316 patients treated with intravenous thrombolysis alone, 18 861 (60%) had available data: age 70±13 years, National Institutes of Health Stroke Scale at baseline (median, 8; interquartile range, 5-14), and 45% men. DNT groups 0 to 20 minutes, 21 to 40 minutes, 41 to 60 minutes, and >60 minutes had 3536 (19%), 5333 (28%), 4856 (26%), and 5136 (27%) patients. National median DNT dropped from 74 minutes in 2004 to 22 minutes in 2019. Shorter DNT had proportional benefit: it increased the odds of achieving modified Rankin score 0 to 1 and decreased the odds of parenchymal hemorrhage/ICH, any ICH, and mortality. Patients with DNT ≤20 minutes, 21 to 40 minutes, and 41 to 60 minutes as compared with DNT >60 minutes had adjusted odds ratios for modified Rankin score 0 to 1 of the following: 1.30 (95% CI, 1.12-1.51), 1.33 (95% CI, 1.15-1.54), and 1.15 (95% CI, 1.02-1.29), and for parenchymal hemorrhage/ICH: 0.57 (95% CI, 0.45-0.71), 0.76 (95% CI, 0.61-0.94), 0.83 (95% CI, 0.70-0.99), respectively. Conclusions Ultrashort initiation of thrombolysis is feasible, improves outcome, and makes treatments safer because of fewer intracerebral hemorrhages. Stroke management should be optimized to initiate thrombolysis as soon as possible optimally within 20 minutes from arrival to a hospital.

Comprehensive Stroke Center Department of Neurology Masaryk Hospital Ustí nad Labem KZ a s Ustí nad Labem Czech Republic

Comprehensive Stroke Center Hospital České Budějovice a s České Budějovice Czech Republic

Comprehensive Stroke Center in Department of Neurology Palacký Medical School and University Hospital Olomouc Czech Republic

Comprehensive Stroke Center University Hospital Hradec KrálovéCharles University Faculty of Medicine in Hradec Králové Czech Republic

Department of Neurology 1st Faculty of Medicine and General University Hospital Charles University Prague Czech Republic

Department of Neurology 2nd Medical School of Charles University and Motol University Hospital Prague Czech Republic

Department of Neurology 3rd Medical School of Charles University and Vinohrady University Hospital Prague Czech Republic

Department of Neurology and AGEL Research and Training Institute Ostrava Vítkovice Hospital Ostrava Czech Republic

Department of Neurology Central Military University Hospital Prague and Motol University Hospital Prague Czech Republic

Department of Neurology Chomutov Hospital KZ a s Chomutov Czech Republic

Department of Neurology Faculty of Medicine in Pilsen Charles University Pilsen Czech Republic

Department of Neurology Hospital Jihlava Jihlava Czech Republic

Department of Neurology Town Hospital Ostrava Ostrava Czech Republic

Department of Neurology University Hospital Brno Brno Czech Republic

Department of Neurology University Hospital Ostrava and Faculty of Medicine at University Ostrava Ostrava Czech Republic

Department of Neurology University Hospital Pilsen Pilsen Czech Republic

Department of Neurosurgery and Neurooncology 1st Faculty of Medicine Charles University Prague Czech Republic

Faculty of Medicine at Masaryk University Brno Czech Republic

International Clinical Research Center and Department of Neurology St Anne's University Hospital in Brno Czech Republic

Military University Hospital Prague Czech Republic

Neurocenter Regional Hospital Liberec Liberec Czech Republic

Zobrazit více v PubMed

Emberson J, Lees KR, Lyden P, Blackwell L, Albers G, Bluhmki E, Brott T, Cohen G, Davis S, Donnan G, et al. Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta‐analysis of individual patient data from randomised trials. Lancet. 2014;384:1929–1935. doi: 10.1016/S0140-6736(14)60584-5 PubMed DOI PMC

Meretoja A, Keshtkaran M, Saver JL, Tatlisumak T, Parsons MW, Kaste M, Davis SM, Donnan GA, Churilov L. Stroke thrombolysis: save a minute, save a day. Stroke. 2014;45:1053–1058. doi: 10.1161/STROKEAHA.113.002910 PubMed DOI

Saver JL. Time is brain–quantified. Stroke. 2006;37:263–266. doi: 10.1161/01.STR.0000196957.55928.ab PubMed DOI

Mikulík R, Kadlecová P, Czlonkowska A, Kobayashi A, Brozman M, Švigelj V, Csiba L, Fekete K, Kõrv J, Demarin V, et al. Factors influencing in‐hospital delay in treatment with intravenous thrombolysis. Stroke. 2012;43:1578–1583. doi: 10.1161/STROKEAHA.111.644120 PubMed DOI

Meretoja A, Strbian D, Mustanoja S, Tatlisumak T, Lindsberg PJ, Kaste M. Reducing in‐hospital delay to 20 minutes in stroke thrombolysis. Neurology. 2012;79:306–313. doi: 10.1212/WNL.0b013e31825d6011 PubMed DOI

Meretoja A, Weir L, Ugalde M, Yassi N, Yan B, Hand P, Truesdale M, Davis SM, Campbell BC. Helsinki model cut stroke thrombolysis delays to 25 minutes in Melbourne in only 4 months. Neurology. 2013;81:1071–1076. doi: 10.1212/WNL.0b013e3182a4a4d2 PubMed DOI

Mikulik R, Bar M, Cernik D, Herzig R, Jura R, Jurak L, Neumann J, Sanak D, Ostry S, Sevcik P, et al. Stroke 2020: implementation goals for intravenous thrombolysis. Eur Stroke J. 2021;6:151–159. doi: 10.1177/23969873211007684 PubMed DOI PMC

Registry of Stroke Care Quality, RES‐Q. FNUSA‐ICRC; 2016. Available at: https://qualityregistry.eu. Accessed April 9, 2020.

Bryndová L, Bar M, Herzig R, Mikulík R, Neumann J, Šaňák D, Škoda O, Školoudík D, Václavík D, Tomek A. Concentrating stroke care provision in the Czech Republic: the establishment of Stroke Centres in 2011 has led to improved outcomes. Health Policy. 2021;125:520–525. doi: 10.1016/j.healthpol.2021.01.011 PubMed DOI

Wahlgren N, Ahmed N, Eriksson N, Aichner F, Bluhmki E, Dávalos A, Erilä T, Ford GA, Grond M, Hacke W, et al. Multivariable analysis of outcome predictors and adjustment of main outcome results to baseline data profile in randomized controlled trials: Safe Implementation of Thrombolysis in Stroke‐MOnitoring STudy (SITS‐MOST). Stroke. 2008;39:3316–3322. doi: 10.1161/STROKEAHA.107.510768 PubMed DOI

Tong X, George MG, Yang Q, Gillespie C. Predictors of in‐hospital death and symptomatic intracranial hemorrhage in patients with acute ischemic stroke treated with thrombolytic therapy: Paul Coverdell Acute Stroke Registry 2008–2012. Int J Stroke. 2014;9:728–734. doi: 10.1111/ijs.12155 PubMed DOI PMC

Strbian D, Michel P, Ringleb P, Numminen H, Breuer L, Bodenant M, Seiffge DJ, Jung S, Obach V, Weder B, et al. Relationship between onset‐to‐door time and door‐to‐thrombolysis time: a pooled analysis of 10 dedicated stroke centers. Stroke. 2013;44:2808–2813. doi: 10.1161/STROKEAHA.113.000995 PubMed DOI

von Kummer R, Broderick JP, Campbell BC, Demchuk A, Goyal M, Hill MD, Treurniet KM, Majoie CB, Marquering HA, Mazya MV, et al. The Heidelberg bleeding classification: classification of bleeding events after ischemic stroke and reperfusion therapy. Stroke. 2015;46:2981–2986. doi: 10.1161/STROKEAHA.115.010049 PubMed DOI

Sedova P, Brown RD, Zvolsky M, Kadlecova P, Bryndziar T, Kubelka T, Weiss V, Volný O, Bednarik J, Mikulik R. Incidence of hospitalized stroke in the Czech Republic: the National Registry of Hospitalized Patient. J Stroke Cerebrovasc Dis. 2017;26:979–986. doi: 10.1016/j.jstrokecerebrovasdis.2016.11.006 PubMed DOI

Tsivgoulis G, Saqqur M, Sharma VK, Brunser A, Eggers J, Mikulik R, Katsanos AH, Sergentanis TN, Vadikolias K, Perren F, et al. Timing of recanalization and functional recovery in acute ischemic stroke. J Stroke. 2020;22:130–140. doi: 10.5853/jos.2019.01648 PubMed DOI PMC

Saver JL, Fonarow GC, Smith EE, Reeves MJ, Grau‐Sepulveda MV, Pan W, Olson DM, Hernandez AF, Peterson ED, Schwamm LH. Time to treatment with intravenous tissue plasminogen activator and outcome from acute ischemic stroke. JAMA. 2013;309:2480–2488. doi: 10.1001/jama.2013.6959 PubMed DOI

Man S, Xian Y, Holmes DN, Matsouaka RA, Saver JL, Smith EE, Bhatt DL, Schwamm LH, Fonarow GC. Association between thrombolytic door‐to‐needle time and 1‐year mortality and readmission in patients with acute ischemic stroke. JAMA. 2020;323:2170–2184. doi: 10.1001/jama.2020.5697 PubMed DOI PMC

Tong X, Wiltz JL, George MG, Odom EC, Coleman King SM, Chang T, Yin X; Paul Coverdell National Acute Stroke Program Team , Merritt RK. A decade of improvement in door‐to‐needle time among acute ischemic stroke patients, 2008 to 2017. Circ Cardiovasc Qual Outcomes. 2018;11:e004981. doi: 10.1161/CIRCOUTCOMES.118.004981 PubMed DOI PMC

Kuhrij LS, Marang‐van de Mheen PJ, van den Berg‐Vos RM, de Leeuw FE, Nederkoorn PJ; Dutch Acute Stroke Audit Consortium . Determinants of extended door‐to‐needle time in acute ischemic stroke and its influence on in‐hospital mortality: results of a nationwide Dutch clinical audit. BMC Neurol. 2019;19:265. doi: 10.1186/s12883-019-1512-2 PubMed DOI PMC

Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, Biller J, Brown M, Demaerschalk BM, Hoh B, et al. 2018 guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2018;49:e46–e110. doi: 10.1161/STR.0000000000000211 PubMed DOI

Messé SR, Khatri P, Reeves MJ, Smith EE, Saver JL, Bhatt DL, Grau‐Sepulveda MV, Cox M, Peterson ED, Fonarow GC, et al. Why are acute ischemic stroke patients not receiving IV tPA? Results from a National Registry. Neurology. 2016;87:1565–1574. doi: 10.1212/WNL.0000000000003198 PubMed DOI PMC

Ido MS, Frankel MR, Okosun IS, Rothenberg RB. Quality of care and its impact on one‐year mortality: the Georgia Coverdell Acute Stroke Registry. Am J Med Qual. 2018;33:86–92. doi: 10.1177/1062860617696578 PubMed DOI

Utilization, Workflow, and Outcomes of Endovascular Thrombectomy in Patients With vs Without Premorbid Disability in a National Registry

Stroke Learning Health Systems: A Topical Narrative Review With Case Examples

Simulation-based team training improves door-to-needle time for intravenous thrombolysis