Efficacy and Safety of Multiple Tenecteplase Doses Compared to Alteplase for Acute Ischemic Stroke Patients, A Pairwise and Frequentist Network Meta-analysis

Abstract

Background: Several clinical trials evaluated the efficacy of Tenecteplase (TNK) for acute ischemic stroke (AIS); however, the comparative efficacy and safety of the different TNK doses against Alteplase (ALT) have not been examined. Therefore, we conducted this network meta-analysis to investigate the efficacy and safety of TNK at doses of 0.1, 0.25, 0.32, and 0.4 mg/kg compared to the standard dose of ALT for AIS patients. Methods: We searched PubMed, Google Scholar, SCOPUS, EBSCO, and Cochrane CENTRAL for randomized controlled trials evaluating any doses of TNK for AIS patients. The efficacy outcomes of this study were the rates of improvement in NIH stroke score (NIHSS) and good modified Rankin scale (mRS), while the safety outcomes were the rates of mortality and symptomatic intracranial hemorrhage (sICH). First, a comparison between TNK (all doses combined) against ALT was made on a random effect meta-analysis model at RevMan software. Then, a frequentist network meta-analysis was done by MetaInsight based on R-shiny and netmeta packages. Results: Ten RCTs with 4037 patients were included in the analysis. In the pairwise meta-analysis, TNK was non-inferior to ALT in the rate of improvement in NIHSS (RR 1.08, 95% CI 0.92 to 1.27) or good mRS (RR 1.07, 95% CI 0.94 to 1.22). TNK was not associated with increased mortality or sICH (RR 0.95 and 0.87, respectively, P>0.05). In the network meta-analysis, the TNK dose of 0.25 mg/kg performed the best and ranked on top of ALT in all outcomes, while the TNK 0.40 dose mg/kg performed the worst and ranked below ALT in all outcomes. Conclusion: For patients with AIS who are eligible for intravenous thrombolysis, TNK at a dose of 0.25 mg/kg achieves the highest efficacy and acceptable safety compared to other TNK doses and the standard dose of ALT.