IMPACT OF DOOR-TO-NEEDLE TIME ON THE EFFECTIVENESS OF ALTEPLASE THROMBOLYSIS IN ISCHEMIC STROKE: A SYSTEMATIC LITERATURE REVIEW
DOI:
https://doi.org/10.66104/k45s1f02Keywords:
Ischemic Stroke; Intravenous thrombolysis; Door-to-needle time; Alteplase; Cerebral reperfusion.Abstract
Introduction: Ischemic Stroke (IS) remains one of the leading causes of morbidity, mortality, and long-term disability worldwide, with intravenous thrombolysis representing one of the main therapeutic strategies for early cerebral reperfusion. In this context, door-to-needle time is considered an important prognostic indicator, since therapeutic delays are directly associated with ischemic injury progression, neurological deterioration, and increased residual functional disability. Objective: To critically analyze contemporary scientific evidence regarding the impact of door-to-needle time on clinical, neurological, functional, and care-related outcomes associated with intravenous thrombolysis in Ischemic Stroke. Methodology: This systematic review was conducted according to PRISMA 2020 recommendations. Searches were performed in the PubMed/MEDLINE, Scopus, Web of Science, Embase, and SciELO databases, including studies published between 2020 and 2025 in Portuguese, English, and Spanish. Observational studies, prospective and retrospective cohorts, multicenter studies, and clinical trials related to door-to-needle time and intravenous thrombolysis in IS were included. Methodological quality was assessed using the Newcastle-Ottawa Scale (NOS). Results: Fourteen studies were included in the final qualitative synthesis. Evidence demonstrated a consistent association between shorter door-to-needle times and better clinical outcomes in IS, including lower in-hospital mortality, improved neurological recovery, greater functional independence, and reduced residual disability. Furthermore, structured care protocols, multidisciplinary integration, availability of advanced neuroimaging, and implementation of digital technologies showed a positive impact on therapeutic efficiency and reduction of delays related to cerebral reperfusion. Final considerations: Reduction of door-to-needle time remains one of the main prognostic determinants related to contemporary management of Ischemic Stroke. Strategies focused on optimizing hospital workflows, strengthening stroke care networks, and incorporating diagnostic and therapeutic technologies appear fundamental to improving clinical outcomes associated with intravenous thrombolysis.
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References
AMERICAN HEART ASSOCIATION. Guidelines for the early management of patients with acute ischemic stroke. Stroke, Dallas, v. 50, n. 12, p. e344-e418, 2019.
CAMPBELL, Bruce C. V. et al. Endovascular therapy for ischemic stroke with perfusion-imaging selection. The New England Journal of Medicine, Boston, v. 372, n. 11, p. 1009-1018, 2015.
GANTI, Latha et al. Impact of door-to-needle time on outcomes in acute ischemic stroke: a multicenter analysis. Journal of Stroke and Cerebrovascular Diseases, New York, v. 32, n. 4, p. 106-114, 2023.
HALL, Christopher N. et al. Tenecteplase versus alteplase for acute ischemic stroke thrombolysis: current perspectives and clinical implications. Stroke Research and Treatment, London, v. 2021, p. 1-10, 2021.
HERPICH, Florian; RINCON, Fred. Management of acute ischemic stroke. Critical Care Medicine, Philadelphia, v. 48, n. 11, p. 1654-1663, 2020.
HIGGINS, Julian P. T. et al. Cochrane handbook for systematic reviews of interventions. 2. ed. Chichester: Wiley, 2022.
IGLESIAS MOHEDANO, Ana María et al. Implementation of stroke protocols and reduction of door-to-needle time in ischemic stroke management. Neurología, Barcelona, v. 35, n. 8, p. 547-554, 2020.
KREMERS, Rosa M. W. et al. Combined reperfusion strategies in acute ischemic stroke: intravenous thrombolysis and mechanical thrombectomy. Frontiers in Neurology, Lausanne, v. 13, p. 1-11, 2022.
LEE, Ji-Hoon et al. Hospital stroke protocols and efficiency in acute ischemic stroke management. BMC Neurology, London, v. 23, n. 1, p. 1-10, 2023.
MALÍKOVÁ, Hana; WEICHERTOVÁ, Renata. Door-to-needle time and functional outcomes in ischemic stroke patients undergoing thrombolysis. Neurological Research, London, v. 44, n. 7, p. 587-595, 2022.
MENG, Xiang et al. Tenecteplase in acute ischemic stroke: pharmacological perspectives and clinical outcomes. Frontiers in Pharmacology, Lausanne, v. 15, p. 1-13, 2024.
NOGUEIRA, Raul G. et al. Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct. The New England Journal of Medicine, Boston, v. 378, n. 1, p. 11-21, 2018.
NOONE, Michelle L. et al. Improving door-to-needle times in acute ischemic stroke through structured institutional protocols. Stroke and Vascular Neurology, London, v. 5, n. 4, p. 321-329, 2020.
PAGE, Matthew J. et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ, London, v. 372, p. n71, 2021.
PAN, Yuesong et al. Early reperfusion and functional outcomes in acute ischemic stroke patients receiving intravenous thrombolysis. International Journal of Stroke, London, v. 17, n. 6, p. 648-657, 2022.
PAN, Yuesong; SHI, Feng. Door-to-needle time and neurological outcomes in acute ischemic stroke: systematic review and meta-analysis. Journal of Neurology, Berlin, v. 268, n. 9, p. 3321-3332, 2021.
POWERS, William J. Acute ischemic stroke management and reperfusion therapy. Stroke, Dallas, v. 51, n. 7, p. e364-e467, 2020.
REVUE MÉDICALE SUISSE. Time is brain: reperfusion and prognosis in acute ischemic stroke. Revue Médicale Suisse, Genève, v. 20, n. 854, p. 112-118, 2024.
SALLUSTIO, Fabio et al. Door-to-needle time as a prognostic indicator in acute ischemic stroke: multicenter contemporary analysis. European Stroke Journal, London, v. 10, n. 1, p. 45-56, 2025.
SANTOS, Cristina Mamédio da Costa; PIMENTA, Cibele Andrucioli de Mattos; NOBRE, Moacyr Roberto Cuce. A estratégia PICO para a construção da pergunta de pesquisa e busca de evidências. Revista Latino-Americana de Enfermagem, Ribeirão Preto, v. 15, n. 3, p. 508-511, 2007.
SOUZA, Marcela Tavares de; SILVA, Michelly Dias da; CARVALHO, Rachel de. Revisão integrativa: o que é e como fazer. Einstein, São Paulo, v. 8, n. 1, p. 102-106, 2010.
WANG, Li et al. Contemporary thrombolytic strategies in acute ischemic stroke: alteplase and tenecteplase perspectives. Journal of Clinical Medicine, Basel, v. 13, n. 2, p. 1-15, 2024.
WANG, Rui et al. Fast-track stroke protocols and reduction of disability in acute ischemic stroke patients. Stroke Research and Treatment, London, v. 2025, p. 1-12, 2025.
WELLS, Gordon A. et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa: Ottawa Hospital Research Institute, 2014.
WHITTEMORE, Robin; KNAFL, Kathleen. The integrative review: updated methodology. Journal of Advanced Nursing, Oxford, v. 52, n. 5, p. 546-553, 2005.
XIONG, Yu et al. Advanced neuroimaging and individualized therapeutic windows in acute ischemic stroke. Frontiers in Neurology, Lausanne, v. 15, p. 1-14, 2024.
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Copyright (c) 2026 André Victor da Silva Jardim, Jordanna Rocha Cardoso Ferro, Leonardo da Paz de Queiroz Marques, Mikael José dos Santos Calmo, Weslley Anderson Barreto Ramos, Felipe Moraes Alecrim
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