What question did this study set out to answer?

This research aims to compare the efficacy and safety of various thrombolytic agents for treating acute ischemic stroke within 4.5 hours of onset.

March 31, 2026Open Access

Comparison of the efficacy and safety of different thrombolytic drugs in the treatment of acute ischemic stroke within 4.5 h: a systematic review and network meta-analysis

Key Points

This research aims to compare the efficacy and safety of various thrombolytic agents for treating acute ischemic stroke within 4.5 hours of onset.
Systematic search of PubMed, Embase, Cochrane, and Web of Science for RCTs
Focused on intravenous thrombolysis in adult AIS patients
Primary outcomes: modified Rankin Scale scores for functional outcomes
Safety outcomes: symptomatic intracranial hemorrhage and mortality
Frequentist network meta-analysis using fixed-effect model to calculate odds ratios.
Reteplase (18 + 18 mg) showed significant advantage over alteplase (OR 1.60; 95% CI 1.27–2.02) for mRS 0–1.
Non-immunogenic recombinant staphylokinase (10 mg) had significant benefit (OR 2.23; 95% CI 1.43–3.48) for mRS 0–1.
Reteplase (18 + 18 mg) improved mRS 0–2 likelihood over alteplase (OR 1.41; 95% CI 1.08–1.84).
Staphylokinase significantly reduced sICH risk compared to tenecteplase (OR 0.31; 95% CI 0.11–0.94).
No significant differences in 90-day mortality among treatments.

Abstract

Background Although several newer thrombolytic agents for acute ischemic stroke (AIS) within 4.5 h of onset have been developed, their relative efficacy, safety, and optimal dosing remain unclear. A comprehensive comparison across all available agents is therefore needed. Methods We systematically searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science for English-language reports of randomized controlled trials (RCTs) published up to December 12, 2025. Eligible trials enrolled adult AIS patients treated with intravenous thrombolysis. Primary outcomes were 90-day excellent (modified Rankin Scale mRS score 0–1) and good (mRS 0–2) functional outcomes. Safety outcomes were symptomatic intracranial hemorrhage (sICH), and all-cause mortality. A frequentist network meta-analysis using a fixed-effect consistency model was conducted to estimate odds ratios (ORs) with 95% confidence intervals (CIs). Results A total of 21 RCTs involving 16,837 patients were included. For achieving mRS 0–1, reteplase (18 + 18 mg) showed a statistically significant advantage over alteplase (0.9 mg/kg) (OR 1.60; 95% CI, 1.27–2.02), and non-immunogenic recombinant staphylokinase (10 mg) demonstrated a statistically significant benefit (OR 2.23; 95% CI, 1.43–3.48). Reteplase (18 + 18 mg) also improved the likelihood of mRS 0–2 compared with alteplase (OR 1.41; 95% CI, 1.08–1.84). For safety, non-immunogenic recombinant staphylokinase significantly reduced sICH risk compared with tenecteplase 0.25 mg/kg (OR 0.31; 95% CI, 0.11–0.94). No significant differences in 90-day mortality were observed among treatments. Conclusion Within the 4.5-h treatment window, reteplase (18 + 18 mg) and non-immunogenic recombinant staphylokinase (10 mg) were associated with the highest probabilities of improved functional outcomes. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420251152754 .

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