Tenecteplase versus alteplase in acute ischemic stroke among the elderly: a meta-analysis of randomized clinical trials

Background: Tenecteplase (TNK) has emerged as a viable alternative to alteplase (TPA) for intravenous thrombolysis (IVT) in acute ischemic stroke (AIS), due to its easier administration, longer half-life, and greater fibrin specificity. While TNK has demonstrated favorable outcomes in the general stroke population relative to TPA, its comparative safety and efficacy in elderly patients (≥80 years) remain unclear. This meta-analysis aims to compare clinical outcomes between TNK and TPA in elderly patients with AIS. Objective: To compare clinical outcomes of iIVT with TNK 0.25 mg/kg versus TPA 0.9 mg/kg in elderly patients with AIS treated within 4.5 hours of symptom onset, focusing on excellent functional outcome and functional independence at 90 days, symptomatic intracranial hemorrhage, and 3-month mortality. Methods: We systematically searched MEDLINE, Embase, and Cochrane Central for randomized controlled trials (RCTs) comparing elderly patients (≥80 years) with AIS randomized to receive intravenous thrombolysis with TNK at a dose of 0.25 mg/kg versus TPA at a dose of 0.9 mg/kg within 4.5 hours of symptom onset. Excellent functional outcome at 3 months was defined as a modified Rankin Scale (mRS) score of 0–1, whereas functional independence as an mRS score of 0–2. Other outcomes include symptomatic intracranial hemorrhage (sICH) and 3-month mortality. We used risk ratio (RR) with 95% confidence intervals (CIs) as the effect size measure for binary outcomes, employing a random‐effects model. Statistical significance was set at p < 0.05. Results: We included five RCTs with a total of 1,331 patients. Females comprised approximately 30% to 52% of the study population. Patients treated with TNK had a higher likelihood of achieving excellent functional outcomes at 90 days compared to those receiving TPA (RR 1.46, 95% CI 1.01–2.09; p=0.045). Functional independence was significantly improved in the TNK group compared to the TPA group (RR 1.15, 95% CI 1.00–1.31; p = 0.045). There was no significant difference in all-cause mortality between the TNK and TPA groups (RR 0.88, 95% CI 0.70–1.10; p=0.270). The risk of sICH was also not significantly different between TNK and TPA (RR 0.70, 95% CI 0.08–5.72; p = 0.743). Conclusion: TNK resulted in higher rates of excellent functional outcomes and functional independence in elderly patients with AIS treated with intravenous thrombolysis within 4.5 hours compared to TPA. The risk of sICH and mortality were similar between groups. Further trials are warranted to confirm these findings.