Abstract 4359642: Efficacy And Safety Of Intravenous Thrombolytics For Acute Ischemic Stroke Beyond 4.5 Hours: A Systematic Review And Meta-Analysis.

The thrombolytic agents are effective and generally used within 4.5 hours after the acute ischemic stroke (AIS). However, the evidence regarding the efficacy and safety of thrombolytics beyond 4.5 hours are limited. This meta-analysis aimed to determine the effect of intravenous thrombolytics (IVT) for AIS beyond 4.5 hours of onset.: A Systematic review and meta-analysis were conducted according to PRISMA guidelines. We searched in 4 databases from inception to May 15, 2025. We identify published trials comparing the use of IVT with non-thrombolysed group in patients who had onset of stroke beyond 4.5 or with wake-up stroke. The main outcomes assessed included 90-day excellent modified Rankin Scale (mRS) score (0-1), mRs 3-6, symptomatic intracraneal hemorrhage (sICH) and Mortality.: Eighteen studies were included with a total of 8,504 patients. After performing a division by subgroups, we found that thrombolysis beyond 4.5 hours was associated with a higher probability of excellent functional outcome (mRS 0-1) compared to non-thrombolysed patients (RR 1.20, 95% CI 1.07–1.35, p=0.002), with significant benefit in the 4.5–24h (RR 1.20, 95% CI 1.07–1.35, p=0.003) and wake-up stroke (RR 1.26, 95% CI 1.01–1.57, p=0.0002) subgroups. IVT was also associated with a reduced risk of mRS 3-6 (RR 0.86, 95% CI 0.78–0.95, p=0.003), particularly in the wake-up stroke group (RR 0.83, 95% CI 0.73–0.95, p=0.007). However, the risk of sICH was significantly higher in the IVT group (RR 3.15, 95% CI 2.39–4.14, p<0.00001) and consistent across all subgroups. No significant differences were found in 90-day mortality.: IVT beyond 4.5 hours including wake up and 4.5 to 24 hours subgroups consistently showed a favorable profile for mRS 0–1 at 90 days, but a higher risk of sICH in the IVT group including all subgroups and with a non-significant increase in 90-day mortality. These findings support the consideration of thrombolytic therapy in selected patients treated in extended time window.: