Neurology. 2026 Mar 24;106(6):e214702. doi: 10.1212/WNL.0000000000214702. Epub 2026 Feb 12.
ABSTRACT
BACKGROUND AND OBJECTIVES: The benefit of IV thrombolysis (IVT) with alteplase before endovascular thrombectomy (EVT) compared with EVT alone has been shown to be limited and time dependent. Data on tenecteplase, its recommended alternative, are limited. We aimed to assess the efficacy and safety of IVT with tenecteplase plus mechanical thrombectomy (TNK + EVT) compared with EVT in patients with large vessel occlusion stroke and determine whether its potential benefit decreases with treatment time.
METHODS: We conducted a retrospective pooled analysis of 2 nationwide, real-world registries of patients with anterior circulation large vessel occlusion stroke within 4.5 hours of known symptom onset and with no contraindication to thrombolysis, treated with TNK + EVT (TETRIS) or EVT (ETIS). The efficacy outcome was the 3-month modified Rankin Scale (mRS) score, analyzed in ordinal and dichotomized (mRS score ≤2) approaches. We used propensity score-weighted logistic regression to assess associations between treatment groups and outcomes of interest.
RESULTS: Among 1,890 patients who were analyzed (TNK + EVT: n = 798; EVT: n = 1,092; median age 73 years [interquartile range 61-82]; 49.6% women), the median expected onset-to-thrombolysis time was 146 minutes [interquartile range 119-180]. More than half of patients (n = 1,063; 56.2%) were admitted first to a primary stroke center. All baseline characteristics were balanced between treatment groups after overlap weighting. Overall, TNK + EVT was associated with better 3-month functional outcome over the full mRS (weighted common odds ratio [OR] 1.53 [95% CI 1.29-1.82]; p < 0.001) and regarding functional independence (propensity score overlap weighting [PSOW]-OR 1.50 [95% CI 1.23-1.84]; p < 0.001). This benefit did not differ statistically between patients admitted first to a primary or comprehensive stroke center (p-interaction = 0.12). There was no significant effect of the expected onset-to-thrombolysis time on the association between TNK + EVT and better functional outcome (p-interaction = 0.11). There were no significant differences in parenchymal hematoma (PSOW-OR 1.29 [95% CI 0.94-1.79]; p = 0.12) and symptomatic intracerebral hemorrhage (PSOW-OR 1.13 [95% CI 0.69-1.86]; p = 0.61) rates.
DISCUSSION: Among patients treated within 4.5 hours of symptom onset, TNK + EVT was associated with better functional outcome than EVT, without safety concerns. This benefit does not seem to be time dependent. These findings support the routine use of tenecteplase before EVT in the early time window.
CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, in patients with stroke due to anterior circulation large vessel occlusion, IV tenecteplase plus thrombectomy is associated with better functional outcomes at 3 months compared with thrombectomy alone.
TRIALS REGISTRATION INFORMATION: NCT03776877 (ETIS registry) and NCT05534360 (TETRIS registry).
PMID:41678809 | DOI:10.1212/WNL.0000000000214702
