We aim to conduct a dose-wise comparison of tenecteplase and alteplase on various efficacy and safety outcomes in patients with acute ischemic stroke. 

Randomized controlled trials (RCTs) exploring the comparative efficacy and safety of tenecteplase and alteplase have been yielding contradictory results on various outcomes. Previous studies have also failed to conduct a dose-wise comparison; this meta-analysis stratifies doses in order to refine our interpretation of outcomes and quantify the benefits and harms of tenecteplase at different doses. 

PubMed/MEDLINE, Cochrane Controlled Register of Trials, and reference lists of the included articles were systematically searched for article retrieval. Several efficacy and safety outcomes were assessed via DerSimonian and Laird random-effects model and reported as Relative Risk at 95% Confidence Interval. Network analysis allowed for a better comparison of doses via indirect collation. Regression analysis was run to identify how outcomes may vary for differing baseline NIHSS scores. 

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 significant 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. Regression analysis demonstrated no significant impact of baseline NIHSS score on functional outcome and mortality. 

Tenecteplase at 0.25 mg/kg dosage 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.