Comparative efficacy of common thrombolytics in acute ischaemic stroke: a network meta-analysis

Introduction: Thrombolytics are widely used for the treatment of ischaemic stroke. Alteplase is the most commonly used thrombolytic. Newer thrombolytics, particularly tenecteplase and reteplase, are currently available. As such, we performed a network meta-analysis to compare the efficacy of thrombolytic agents. Methods: A systematic search of PubMed MEDLINE, Embase, Scopus and the Cochrane Library was conducted from database inception to 31 August 2024 to identify studies evaluating the efficacy of different thrombolytic agents. Studies analysing thrombolytic effects in terms of mortality or modified Rankin Scale (mRS) in patients with acute ischaemic stroke were included. Comparative efficacy on the two main outcomes was then analysed using a random effects network meta-analysis. Results: Twenty-three studies were included with a pooled patient cohort of 25,379 patients. In patients with AIS, the network meta-analysis demonstrated no difference in terms of mortality outcomes across the thrombolytics. In terms of functional outcomes, reteplase was associated with a better functional outcome compared to alteplase (odds ratio [OR] 1.37, 95% confidence interval [CI] 1.06, 1.77) and urokinase (OR 1.54, 95% CI 1.14, 2.08). These results were analysed regardless of the duration of follow-up. Further sensitivity analysis based on 90-day follow-up showed no significant differences in terms of mortality outcomes, while reteplase showed similar functional outcomes compared to alteplase and tenecteplase. Conclusion: Reteplase appeared to be associated with better functional outcomes and had similar mortality rates compared to alteplase. Further head-to-head randomised controlled trials between the thrombolytic agents are needed to confirm these findings.