Introduction: Acute ischemic stroke (AIS) is a leading cause of death and disability. While intravenous Alteplase within 4.5 hours improves outcomes, many patients remain ineligible. Tenecteplase, a genetically modified tissue plasminogen activator, offers potential advantages, including greater fibrin specificity, longer half-life, and single-bolus administration. Advanced imaging has enabled thrombolysis in a delayed window (4.5–24 hours), but direct comparisons between Tenecteplase and Alteplase in this setting are lacking. We conducted an indirect comparison of these agents, using best medical therapy as a common comparator. Methods: A systematic review of PubMed, Embase, Scopus, and ClinicalTrials.gov identified randomized controlled trials (RCTs) enrolling adults with AIS treated beyond 4.5 hours from onset. Eligible trials compared Tenecteplase or Alteplase versus best medical therapy and reported ≥1 of the following: modified Rankin Scale (mRS) at 90 days, symptomatic intracranial hemorrhage (sICH), or 90-day mortality. Non-randomized studies and direct Tenecteplase–Alteplase comparisons were excluded. Log-transformed risk ratios and standard errors were calculated, and indirect comparisons were performed using the Bucher method. All statistical analyses were conducted using Jamovi software. Results: Six RCTs compared Tenecteplase with the best medical therapy, and seven compared Alteplase with the best medical therapy in the delayed window. Indirect comparison showed no significant difference between Tenecteplase and Alteplase for excellent functional outcome (mRS 0–1, RR 0.95; 95% CI 0.85–1.07) or favorable outcome (mRS 0–2, RR 0.95; 95% CI 0.82–1.10). Rates of sICH were similar (RR 0.78; 95% CI 0.28–2.21), as were 90-day mortality rates (RR 0.78; 95% CI 0.43–1.41). Conclusions: In this first indirect comparison of Tenecteplase and Alteplase for delayed-window thrombolysis, efficacy and safety profiles appeared comparable. While these findings support the potential interchangeability of agents in this setting, they are limited by the absence of direct head-to-head trials. Large, randomized comparative studies are needed to guide optimal thrombolysis selection in the delayed window.
Thatikala et al. (Thu,) studied this question.