Artigo de Revisão

Efficacy and safety of delayed thrombolysis for ischemic stroke within 4.5-24h: A systematic review and meta-analysis of randomized controlled trials

Publicado em: 2025

Autores

  • Jesús Fernando Briceño-Domínguez
    Departamento de Medicina Interna, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México City, Mexico.
  • Grecia Bejarano-Carabeo
    Departamento de Nefrología, Instituto Nacional de Cardiología "Ignacio Chávez", México City, Mexico.
  • Rodrigo Góes de Oliveira Galvão
    Escola Superior de Ciências da Saúde (ESCS), Brasília, Brazil.
  • Barbara Alessandra Jacobs Rodrigues
    Universidad Católica Boliviana San Pablo, Santa Cruz, Bolivia.
  • Alejandro Quintero-Villegas
    Elmezzi Graduate School of Molecular Medicine, Feinstein Institutes for Medical Research, Northwell, Manhasset, New York, United States; Institute of Health System Science, Feinstein Institutes for Medical Research, Northwell, Manhasset, New York, United States; Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Northwell, Manhasset, New York, United States.
  • Sergio Iván Valdes-Ferrer
    Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Northwell, Manhasset, New York, United States; Dirección de Proyectos de Investigación en Salud, Secretaria de Salud, México City, Mexico; Escuela de Medicina y Ciencias de la Salud, Tecnológico de Monterrey, México City, Mexico. Electronic address: sergio.valdes@salud.gob.mx.

Resumo

The efficacy and safety of thrombolytics within the first 4.5h of ischemic stroke symptom onset are well documented; however, evidence beyond this timeframe remains contentious. To assess the efficacy and safety of delayed thrombolysis (4.5-24-h window) for ischemic stroke. We conducted a systematic search to identify studies comparing thrombolytics to placebo or standard care in ischemic stroke patients treated within 4.5-24h of symptom onset. The primary outcome was functional independence at 90 days, with additional efficacy outcomes exploring recanalization and reperfusion at 24h, as well as safety outcomes of 90-day mortality and symptomatic intracranial hemorrhage. The statistical analysis was performed using R studio. We included five randomized controlled trials with 1398 patients. The mean age was 70.2 years, 61% were male, and the median NIHSS score was 10.2. Compared with controls, thrombolysis improved functional independence at 90 days (OR 1.32; 95% CI: 1.06-1.63; p=0.01; I=0%), although it increased the risk of symptomatic intracranial hemorrhage (OR 2.5; 95% CI: 1.10-5.71; p=0.02; I=0%). No significant difference in mortality at 90 days was observed (OR 1.15; 95% CI: 0.84-1.57; p=0.39; I=0%). In ischemic stroke, thrombolytics administered within 4.5-24h improve functional independence at 90 days, also increasing the risk of symptomatic intracranial hemorrhage. At this point, careful and individualized patient selection, including advanced imaging, is mandatory for thrombolysis beyond the conventional 4.5-h treatment window.

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