Key result
IV tPA in imaging-selected wake-up stroke fails to improve functional outcomes while increasing bleeding risk.
Why the study?
Patients with wake-up stroke are often excluded from intravenous thrombolysis due to unknown symptom onset time, and the effectiveness and safety of IV tPA in this population identified by advanced imaging remain unclear.
Does intravenous thrombolysis using tissue plasminogen activator improve favorable functional outcomes in adult patients with wake-up stroke selected by advanced imaging?
Meta-Analysis (n=6,379)
Yes
Does intravenous thrombolysis using tissue plasminogen activator improve favorable functional outcomes in adult patients with wake-up stroke selected by advanced imaging?
Relative Risk: 1.17 (95% CI 0.79–1.74)
p-value: p=0.42
In this meta-analysis, intravenous thrombolysis in patients with wake-up stroke did not significantly improve functional outcomes or mortality in observational data, but was associated with an increased risk of symptomatic intracerebral hemorrhage.
Does not support IV-tPA in advanced imaging-selected wake-up stroke; challenges assumptions of net benefit and warrants refined selection trials.
Background: Intravenous tissue plasminogen activator (IV tPA) is the established standard therapy for acute ischemic stroke when administered within 4.5 hours of symptom onset. Nevertheless, patients with wake-up stroke (WUS), for whom the exact time of symptom onset cannot be determined, are often excluded from IV tPA treatment under conventional time-based criteria. This systematic review and meta-analysis aim to assess the effectiveness, safety, and prognostic outcomes of IV tPA in patients with WUS identified through advanced imaging techniques. Methods: Relevant searches of databases were performed in accordance with the PRISMA guideline. Randomized controlled trials (RCTs) and cohort studies comparing IV-tPA in WUS patients were included. Outcomes include functional independence (modified Rankin Scale [mRS]), symptomatic intracerebral hemorrhage (sICH), and 90-day mortality. Risk of bias/study quality was appraised using Cochrane RoB and the Newcastle-Ottawa Scale. Pooled relative risks were used as point estimates using Review Manager v5.4.1, and funnel plots assessed publication bias. Results: Nineteen studies (17 cohort and 2 randomized controlled trials) involving a total of 6,379 WUS patients were included, with most using advanced imaging, which was magnetic resonance imaging (MRI). Among those treated with IV-tPA, 44% achieved modified Rankin Scale (mRS) 0–1 (95%CI 0.31–0.58), and 55% achieved mRS 0–2 (95%CI 0.44–0.65). The symptomatic intracerebral hemorrhage (sICH) rate was 2% (95%CI 0.01-0.04), and 90-day mortality was 4% (95%CI 0.02-0.08). In the included observational study, compared to controls, IV tPA did not significantly improve outcomes, including mRS 0–1, mRS 0–2, or mortality, but significantly increased the risk of sICH (RR=3.94;95%CI 2.79–5.55; p<0.01). There was substantial heterogeneity, with minimal risk of publication bias across studies. Conclusion: The use of IV tPA in wake-up stroke patients was not associated with significant benefits in functional outcomes or mortality, but was associeted with an increased risk of sICH.
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Salim et al. (2026) conducted a meta-analysis in Wake-up stroke (n=6,379). Intravenous tissue plasminogen activator (IV tPA) vs. Placebo or standard medical care without thrombolytic therapy was evaluated on Favorable functional outcome (mRS score 0-1 at 90 days in observational studies) (RR 1.17, 95% CI 0.79-1.74, p=0.42). Intravenous tissue plasminogen activator in wake-up stroke patients selected by advanced imaging did not significantly improve functional outcomes but increased the risk of symptomatic intracerebral hemorrhage.
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