Safety Outcomes Following Intravenous Thrombolysis in Acute Ischemic Stroke: A Systematic Review and Network Meta-analysis.

2025-09-30
CNS drugs 40(2)
- Xuefan Yao
- Kehui Ma
- Benke Zhao
- Aini He
- Wei Sun
- Jiaxin Gao
- Houlin Lai
- Xue Wang
- Yuan Wang
- Haiqing Song

PubMed: 41026449
DOI: 10.1007/s40263-025-01228-x

Study Design

Type: Systematic Review
Population: acute ischemic stroke (AIS) patients
Methods: systematic review and meta-analysis of phase 3 randomized controlled trials on IVT in AIS from Embase, Ovid Medline, and Cochrane Library
Duration: 3-month mortality

Background

Safety outcomes following intravenous thrombolysis (IVT) impact overall efficacy in acute ischemic stroke (AIS), yet safety profiles of various IVT treatments remain less studied. In this study, we ranked safety profiles of various IVT treatments through a systematic review and meta-analysis of safety outcomes following IVT in AIS.

Methods

This network meta-analysis was registered in the International Prospective Register of Systematic Reviews (PROSPERO; no. CRD42024544617). Phase 3 randomized controlled trials on IVT in AIS from Embase, Ovid Medline, and Cochrane Library were included. Primary outcomes included total serious adverse events (SAEs), symptomatic intracranial hemorrhage (sICH), and 3-month mortality.

Results

Network meta-analysis involved 21 studies for total SAEs, 21 for sICH, and 34 for mortality with no heterogeneity (I² = 0%; I² = 0%; I² = 15.86%). Compared with non-thrombolysis, alteplase 0.9 mg/kg and tenecteplase 0.25 mg/kg were associated with more SAEs (risk difference [RD] 0.03, 95% confidence interval [CI] 0.01-0.05; RD 0.04, 95% CI 0.01-0.06), sICH (RD 0.02, 95% CI 0.01-0.03; RD 0.02, 95% CI 0.01-0.03), and mortality (RD 0.01, 95% CI 0.00-0.03; RD 0.02, 95% CI 0.00-0.03). Nonimmunogenic recombinant staphylokinase (nSta) 10 mg resulted in fewer SAEs than non-thrombolysis (RD - 0.11, 95% CI - 0.21 to - 0.01), recombinant human prourokinase (rhPro-UK) 35 mg (RD - 0.12, 95% CI - 0.22 to - 0.02), alteplase 0.9 mg/kg (RD - 0.14, 95% CI - 0.23 to - 0.04), and tenecteplase 0.25 mg/kg (RD - 0.15, 95% CI - 0.24 to - 0.05) and less sICH than tenecteplase 0.25 mg/kg (RD - 0.05, 95% CI - 0.10 to 0.00). Although rhPro-UK 35 mg resulted in more sICH than non-thrombolysis (RD 0.01, 95% CI 0.00-0.02), it was associated with a lower rate of sICH compared with alteplase 0.9 mg/kg (RD - 0.01, 95% CI - 0.02 to 0.00) and tenecteplase 0.25 mg/kg (RD - 0.01, 95% CI - 0.02 to - 0.01). Compared with alteplase 0.6 mg/kg, alteplase 0.9 mg/kg and tenecteplase 0.25 mg/kg resulted in more SAEs (RD 0.04, 95% CI 0.01-0.07; RD 0.05, 95% CI 0.01-0.08) and sICH (RD 0.01, 95% CI 0.00-0.02; RD 0.02, 95% CI 0.01-0.03). When administered beyond 4.5 h with tissue window assessment, tenecteplase 0.25 mg/kg and alteplase 0.6 mg/kg were not associated with higher rates of mortality compared with non-thrombolysis.

Conclusions

Alteplase 0.6 mg/kg, rhPro-UK 35 mg, and nSta 10 mg were safer IVT options. Tenecteplase 0.25 mg/kg and alteplase 0.6 mg/kg were preferable beyond 4.5 h with tissue window assessment.