Introduction: Intravenous thrombolysis with alteplase is the global standard of care for patients with acute ischemic stroke (AIS) within 4.5 hours; however, tenecteplase may offer potential advantages. A small proportion of patients are eligible to receive thrombolysis within this window. Methods: We systematically searched MEDLINE, Embase, Cochrane Library, and ClinicalTrials.gov for randomized clinical trials (RCTs) comparing tenecteplase and alteplase in patients with AIS beyond 4.5 hours from symptom onset or last known well. Best medical therapy (BMT) was included as a reference node in the network. A Bayesian random-effects network meta-analysis was performed to estimate risk ratios (RRs) with 95% credible intervals (CrIs). Treatments were ranked using the surface under the cumulative ranking curve (SUCRA). Results: A total of 13 RCTs including 3,625 patients were analyzed, of which 1,799 (49.6%) received BMT, 979 (26.9%) tenecteplase, and 848 (23.4%) alteplase. Compared with BMT, tenecteplase (OR 1.34; 95% CrI, 1.09–1.67) and alteplase (OR 1.54; 95% CrI, 1.21–1.90) were associated with higher odds of excellent functional outcomes, with no significant difference between the two agents (RR 0.88; 95% CrI, 0.65–1.23). Alteplase was linked to a significantly higher risk of symptomatic intracranial hemorrhage (sICH) compared with BMT (OR 4.62; 95% CrI, 1.71–15.67), whereas no significant difference was observed between BMT and tenecteplase. 90-day mortality did not differ significantly across treatment strategies. SUCRA analysis ranked tenecteplase as the most effective for functional outcomes, while BMT was safest for reducing sICH and mortality, followed by tenecteplase and alteplase. Conclusions: Both tenecteplase and alteplase improve excellent functional outcomes compared with BMT in patients with AIS beyond 4.5 hours. Functional outcomes did not differ significantly between tenecteplase and alteplase. However, alteplase was associated with a higher risk of sICH, whereas tenecteplase appeared safer and ranked as the most effective option for functional recovery. 90-day mortality was comparable across strategies.
Marinheiro et al. (Thu,) studied this question.