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Background <p>The benefits and risks of intravenous thrombolysis (IVT) with alteplase for acute ischemic stroke (AIS) beyond 4.5 h are unclear. Decision-making is further limited by the lack of comparisons between imaging strategies used for patient selection, including magnetic resonance imaging with diffusion-weighted imaging (MRI/DWI) and perfusion-guided approaches such as MRI with perfusion-weighted imaging (MRI/PWI) or computed tomography perfusion (CTP). This study aims to evaluate the efficacy and safety of alteplase administered beyond 4.5 h and to compare MRI/DWI- and perfusion-guided IVT.</p> Methods <p>Databases were searched for RCTs enrolling AIS patients treated with alteplase beyond 4.5 h. Efficacy outcomes included excellent (mRS 0–1) and favorable (mRS 0–2) functional outcomes at 90&#xa0;days, and major neurological improvement up to 72 h. Safety outcomes included any intracranial hemorrhage (aICH), symptomatic ICH (sICH), parenchymal hemorrhage (PH), and 90-day mortality.</p> Results <p>Seven RCTs comprising 1685 patients were included. There were no differences between imaging strategies in any efficacy or safety outcome. Alteplase administered beyond 4.5 h was associated with higher rates of excellent (RR 1.24; 95% CI 1.12–1.38) and favorable (RR 1.17; 95% CI 1.09–1.26) functional outcomes, and increased major neurological improvement (RR 1.28; 95% CI 1.11–1.49). The risks of aICH (RR, 2.82; 95% CI 1.17–6.80), sICH (RR, 3.31; 95% CI 1.42–7.74), and PH (RR, 2.95; CI 95% 1.33–6.53) were higher in the alteplase group, while mortality showed no difference (RR 1.27; 95% CI 0.91–1.76).</p> Conclusion <p>This network meta-analysis did not detect a&#xa0;statistically significant difference between perfusion-guided and DWI/FLAIR mismatch–guided selection; however, this comparison was indirect, based on a&#xa0;limited number of trials, and not powered to demonstrate equivalence, and should not be interpreted as evidence that the two paradigms are interchangeable.</p>

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Magnetic Resonance Imaging/Diffusion-Weighted Imaging-Guided Versus Perfusion-Guided Intravenous Thrombolysis with Alteplase Beyond 4.5-Hour Window: a Network Meta-Analysis of Randomized Controlled Trials

  • 期刊论文

  • 发表日期：

    2026年6月29日

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  • Ocílio Ribeiro Gonçalves,
  • Gabriel Caruso Novaes Tudella,
  • Leonardo Januário Campos Cardoso,
  • Giovana Menegucci,
  • Augusto Utida Klostermann,
  • Luis Felipe Porto,
  • Carlos Daniel Santiago Azevedo,
  • Anderson Matheus Pereira da Silva,
  • Társis Vinícius Cronemberger,
  • Jagkirat Singh,
  • Wei Jun Lee,
  • Leonardo Di Cosmo,
  • Mariana Letícia de Bastos Maximiano,
  • Ahmet Gunkan,
  • Thanh Nguyen,
  • Adam Andrew Dmytriw,
  • Guillaume Turc,
  • Frédéric Clarençon,
  • Luca Scarcia

摘要

Background

The benefits and risks of intravenous thrombolysis (IVT) with alteplase for acute ischemic stroke (AIS) beyond 4.5 h are unclear. Decision-making is further limited by the lack of comparisons between imaging strategies used for patient selection, including magnetic resonance imaging with diffusion-weighted imaging (MRI/DWI) and perfusion-guided approaches such as MRI with perfusion-weighted imaging (MRI/PWI) or computed tomography perfusion (CTP). This study aims to evaluate the efficacy and safety of alteplase administered beyond 4.5 h and to compare MRI/DWI- and perfusion-guided IVT.

Methods

Databases were searched for RCTs enrolling AIS patients treated with alteplase beyond 4.5 h. Efficacy outcomes included excellent (mRS 0–1) and favorable (mRS 0–2) functional outcomes at 90 days, and major neurological improvement up to 72 h. Safety outcomes included any intracranial hemorrhage (aICH), symptomatic ICH (sICH), parenchymal hemorrhage (PH), and 90-day mortality.

Results

Seven RCTs comprising 1685 patients were included. There were no differences between imaging strategies in any efficacy or safety outcome. Alteplase administered beyond 4.5 h was associated with higher rates of excellent (RR 1.24; 95% CI 1.12–1.38) and favorable (RR 1.17; 95% CI 1.09–1.26) functional outcomes, and increased major neurological improvement (RR 1.28; 95% CI 1.11–1.49). The risks of aICH (RR, 2.82; 95% CI 1.17–6.80), sICH (RR, 3.31; 95% CI 1.42–7.74), and PH (RR, 2.95; CI 95% 1.33–6.53) were higher in the alteplase group, while mortality showed no difference (RR 1.27; 95% CI 0.91–1.76).

Conclusion

This network meta-analysis did not detect a statistically significant difference between perfusion-guided and DWI/FLAIR mismatch–guided selection; however, this comparison was indirect, based on a limited number of trials, and not powered to demonstrate equivalence, and should not be interpreted as evidence that the two paradigms are interchangeable.