Efficacy and safety analysis of tenecteplase vs. alteplase in very elderly patients with acute ischemic stroke: a systematic review and meta-analysis of randomized trials.
Internal and Emergency Medicine · 2026-09-07 · Meta-analysis
Abstract
Tenecteplase (TNK) is a modified variant of alteplase (TPA) that offers advantages such as a long plasma half-life and high fibrin specificity. Previous studies have demonstrated the noninferiority of TNK to TPA in patients with acute ischemic stroke (AIS). Although very elderly patients (aged ≥ 80 years) represent a significant proportion of AIS cases, research on the safety and efficacy of TNK in this population remains limited. Therefore, this study aimed to evaluate the comparative efficacy and safety of TNK versus TPA in treating AIS in very elderly patients. We conducted a meta-analysis of randomized controlled trials (RCTs) from Embase, PubMed, and the Cochrane Library up to May 20th, 2026. The outcomes included modified Rankin Scale (mRS) scores of 0-1 and 0-2 at 90 days, symptomatic intracranial hemorrhage (SICH), all-cause mortality, and parenchymal hematoma. We also performed subgroup analysis to assess the effects of patient race. We utilized mainly Review Manager 5.4 software to conduct the data synthesis and statistical analysis. Five RCTs (EXTEND-IA TNK, AcT, ATTEST-2, TRACE-2, and ORIGINAL) involving 1307 very elderly patients were included. Pooled analysis showed that TNK was associated with higher odds of excellent and good functional outcomes at 90 days compared with TPA (excellent: odds ratio (OR) 1.85, 95% confidence interval (CI) 1.06-3.23, p = 0.03, I2 = 75%; good: OR 1.35, 95% CI: 1.06-1.71, p = 0.01, I2 = 3%). Leave-one-out sensitivity analysis showed that the association between TNK and excellent functional outcomes was no longer statistically significant after exclusion of the ORIGINAL trial (OR 1.38, 95% CI 0.91-2.08, p = 0.13, I2 = 52%). No statistically significant differences were observed between TNK and TPA in SICH (OR 1.00, 95% CI 0.54-1.89, I2 = 0%), 90-day mortality (OR 0.84, 95% CI 0.63-1.11, I2 = 0%), or parenchymal hematoma (OR 0.73, 95% CI 0.30-1.74, I2 = 5%). In this pooled analysis of noninferiority-designed RCTs, TNK was associated with a trend toward improved functional outcomes compared with TPA in very elderly patients with AIS. However, the statistical significance of the excellent functional outcome was dependent on the inclusion of the ORIGINAL trial, and the association was no longer significant after its exclusion. This finding, combined with the high heterogeneity and small sample sizes, and the high risk of bias related to deviations from intended interventions in most included trials, suggests that the results should be regarded as hypothesis-generating. As all included trials were designed as noninferiority studies, adequately powered superiority trials are warranted to confirm the potential benefit of TNK over TPA in this population.
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Tags
Antithrombotics & thrombolytics · Mortality & survival · Older adults · Quality of life & function · Thrombolytics
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