A systematic search of PubMed, Web of Science, Embase, and Cochrane Library was performed to identify randomized controlled trials and prospective studies enrolling patients with minor ischemic stroke (NIHSS ≤5). Eligible studies compared intravenous tenecteplase with alteplase or medical therapy. The primary outcome was functional independence at 90 days (mRS 0–1); secondary outcomes included symptomatic intracranial hemorrhage (sICH) and all-cause mortality at 90 days. Risk of bias was assessed using the Cochrane RoB 2 tool for randomized trials and the Newcastle–Ottawa Scale for observational studies. Pooled odds ratios with 95% confidence intervals were estimated using random-effects models, and heterogeneity was quantified with the I² statistic.

A total of 1,293 studies were screened, of which five studies met the inclusion criteria (three randomized trials and two cohorts)  comprising 1,677 patients (844 tenecteplase, 833 comparators). Tenecteplase was not associated with a higher likelihood of achieving mRS 0–1 compared with alteplase (OR 1.20, 95% CI, 0.84–1.70; I² = 0%) or  with medical therapy alone (OR 0.90, 95% CI, 0.68–1.19; I² = 0%). In secondary analyses, two studies (n=946) suggested a borderline increased risk of sICH with tenecteplase vs medical therapy  (OR 4.00, 95% CI 0.98–16.26; p=0.053; I²=0%). Mortality did not significantly differ between tenecteplase and alteplase (2 trials, n=526; OR 0.67, 95% CI 0.28–1.60; I²=32%).