Comparative efficacy and safety of tenecteplase and alteplase in acute ischemic stroke: A pairwise and network meta-analysis of randomized controlled trials

Background: Studies on tenecteplase have been yielding mixed results for several important outcomes at different doses, thus hampering objective guideline recommendations in acute ischemic stroke management. This meta -analysis stratifies doses in order to refine our interpretation of outcomes and quantify the benefits and harms of tenecteplase at different doses. Methods: PubMed/MEDLINE, the Cochrane Library, and reference lists of the included articles were systemati-cally searched. Several efficacy and safety outcomes were pooled and reported as risk ratios (RRs) with 95% confidence intervals (CIs). Network meta-analysis was used to find the optimal dose of tenecteplase. Meta -regression was run to investigate the impact of baseline NIHSS scores on functional outcomes and mortality. Results: Ten randomized controlled trials with a total of 4140 patients were included. 2166 (52.32%) patients were enrolled in the tenecteplase group and 1974 (47.68%) in the alteplase group. Tenecteplase at 0.25 mg/kg dose demonstrated significant improvement in excellent functional outcome at 3 months (RR 1.14, 95% CI 1.04-1.26), and early neurological improvement (RR 1.53, 95% CI 1.03-2.26). There was no statistically sig-nificant difference between tenecteplase and alteplase in terms of good functional outcome, intracerebral hemorrhage (ICH), symptomatic intracerebral hemorrhage (sICH), and 90-day mortality at any dose. Meta -regression demonstrated superior tenecteplase efficacy with increasing stroke severity, however, the results were statistically nonsignificant. Conclusions: Tenecteplase at 0.25 mg/kg dose is more efficacious and at least as safe as alteplase for stroke thrombolysis. Newer analyses need to focus on direct comparison of tenecteplase doses and whether tenecteplase is efficacious at longer needle times.