To assess the safety and efficacy of Intravenous Thrombolysis (IVT) without Mechanical Thrombectomy (MT) in Acute Ischemic Stroke (AIS) patients presenting beyond 4.5 hours of symptom onset when compared to standard medical management alone. 

Current guidelines recommend the use of IVT in AIS patients presenting within 4.5 hours of symptom onset. MR Witness and WAKE UP trials implemented the use of MRI diffusion-FLAIR mismatch to identify eligible IVT candidates. Recently, the TRACE trial done in China revealed the benefit of IVT in patients with large vessel occlusions (LVO) who presented between 4.5 and 24 hours, and were unable to undergo MT. 

A thorough literature search, using PubMed, Embase, and Cochrane, was conducted from inception till October 2024 to include seven studies (observational and RCTs) analyzing the benefit and safety of IVT in AIS patients presenting beyond 4.5 hrs or with unknown symptom onset. Functional outcomes, sICH, and mortality were the main outcomes. Comprehensive Meta-Analysis (CMA) version 3.0 was used.

A total of 1575 participants were included with 806 participants in the intervention group and 769 in the control group. The group that received IVT (but no MT) had a more favorable functional outcome (OR= 1.44, 95% [CI=1.169 - 1.783], p= 0.001) and functional independence at 90 days than the group that received standard medical management. There was a significantly higher risk of sICH in the intervention group (OR= 3.703, 95% [CI= 1.583 - 8.664], p=0.003) compared to the control group. There was no significant difference in mortality between the two cohorts.

IVT has the potential to provide significant benefit to AIS patients, particularly LVO (without MT), presenting up to 24 hours. Given the higher incidence of sICH, risks, and benefits need to be weighed against each other so that eligible patients can receive IVT and profound disability can be prevented.