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

American Heart Association

Final ID: MP1204

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

Abstract Body (Do not enter title and authors here):

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.

Yanez Mata, Daniela Alejandra ( Universidad Autnoma de Baja California , Tijuana , Mexico )
Aragon Cortes, Amiel ( Universidad Autnoma de Baja California , Tijuana , Mexico )
Velarde Sarabia, Damaris ( Universidad Autnoma de Baja California , Tijuana , Mexico )
Perez Almaraz, Diana ( Universidad Autnoma de Baja California , Tijuana , Mexico )
Calderon-fernandez, Adolfo ( Universidad Autnoma de Baja California , Tijuana , Mexico )
Valenzuela-rangel, Alder ( Universidad Autnoma de Baja California , Tijuana , Mexico )
Ramos Pillado, Francisco ( Universidad Autnoma de Baja California , Tijuana , Mexico )
Verber Arano, Mario Alberto ( Universidad Autnoma de Baja California , Tijuana , Mexico )
Haro Adame, Julio Alfredo ( Universidad Autnoma de Baja California , Tijuana , Mexico )
Natera, Dilmareth ( University of Minnesota , Shakopee , Minnesota , United States )
Cueva, Luis E. ( Universidad Nacional de Piura , Piura , Peru )
López Mena, Diego ( Instituto Nacional de Neurologia y Neurocirujia , Ciudad de Mexico , Mexico )

Author Disclosures:

Daniela Yanez Mata: