Effect of Baseline ASPECTS on Tenecteplase Efficacy Before Thrombectomy in Acute Large-Vessel Occlusion Stroke: A Post Hoc Analysis of the BRIDGE-TNK Randomized Trial.
In this post hoc analysis of the BRIDGE-TNK trial, intravenous tenecteplase before thrombectomy showed a signal of benefit in patients with ASPECTS <8, whereas no functional improvement and possible safety concerns were seen in those with ASPECTS 8-10.
Key Findings
Results
Tenecteplase plus thrombectomy significantly improved functional independence compared to thrombectomy alone in patients with ASPECTS <8, but not in those with ASPECTS 8-10.
In the ASPECTS <8 subgroup, the adjusted risk ratio (aRR) for functional independence (mRS 0-2 at 90 days) was 1.67 (95% CI 1.18-2.35)
In the ASPECTS 8-10 subgroup, the aRR for functional independence was 0.99 (95% CI 0.84-1.17)
The treatment-by-ASPECTS interaction was statistically significant (p-interaction = 0.007)
241 patients (43.8%) had ASPECTS <8 and 309 had ASPECTS 8-10 among the 550 total patients analyzed
Results
Rates of symptomatic intracranial hemorrhage (sICH) at 48 hours did not differ significantly between treatment groups in either ASPECTS subgroup.
In the ASPECTS <8 subgroup, sICH rates were 10.0% (tenecteplase plus thrombectomy) vs 11.2% (thrombectomy alone)
In the ASPECTS 8-10 subgroup, sICH rates were 7.5% (tenecteplase plus thrombectomy) vs 2.8% (thrombectomy alone)
The treatment-by-ASPECTS interaction for sICH was not statistically significant (p-interaction = 0.11)
Results
90-day mortality was numerically higher with tenecteplase plus thrombectomy in the ASPECTS 8-10 subgroup, with a statistically significant interaction term.
In the ASPECTS 8-10 subgroup, the aRR for 90-day mortality was 1.89 (95% CI 0.99-3.61)
90-day mortality was comparable between treatment groups in the ASPECTS <8 subgroup
The treatment-by-ASPECTS interaction for mortality was statistically significant (p-interaction = 0.04)
The confidence interval for the mortality aRR in ASPECTS 8-10 crossed 1.0, indicating the finding did not reach conventional statistical significance for that subgroup alone
Methods
The study population consisted of 550 acute large-vessel occlusion stroke patients treated within 4.5 hours of last known well across China from May 2022 to September 2024.
This was a post hoc analysis of the BRIDGE-TNK randomized trial (ClinicalTrials.gov: NCT04733742)
The ASPECTS <8 subgroup had a median age of 69 years (IQR 61-77) and was 56.4% male
The ASPECTS 8-10 subgroup had a median age of 70 years (IQR 61-77) and was 59.5% male
Regression models incorporating a treatment-by-ASPECTS interaction term were used for all primary analyses
Discussion
The authors identified ASPECTS as a potential effect modifier for tenecteplase efficacy before thrombectomy, suggesting the benefit of bridging thrombolysis may be restricted to patients with more extensive early ischemic changes.
The conventional expectation would be that patients with less ischemic injury (higher ASPECTS) would benefit more from reperfusion therapy, making the observed pattern of greater benefit in ASPECTS <8 counterintuitive
The authors note this is an exploratory post hoc analysis and that prospective confirmation in randomized trials is required before practice change
Possible safety concerns in the ASPECTS 8-10 group were flagged based on the numerically higher mortality signal
What This Means
This research analyzed data from the BRIDGE-TNK trial, a study conducted in China that examined whether giving a clot-dissolving drug (tenecteplase) through an IV before a mechanical clot-removal procedure (thrombectomy) improves outcomes in stroke patients with a blocked large blood vessel. The researchers specifically looked at whether the amount of early brain injury visible on brain scans — measured by a score called ASPECTS — changed how well the drug worked. Patients were divided into two groups: those with more extensive early brain injury (ASPECTS below 8) and those with less injury (ASPECTS 8-10).
Surprisingly, the combination of tenecteplase plus thrombectomy led to significantly better functional outcomes at 90 days compared to thrombectomy alone only in patients who already had more extensive brain injury (ASPECTS <8), with a 67% higher rate of functional independence. In contrast, patients with less brain injury (ASPECTS 8-10) showed no improvement in functional outcomes and had a numerically higher rate of death (though this did not reach clear statistical significance on its own). Rates of serious bleeding in the brain were not significantly different between treatment groups in either patient category.
This research suggests that ASPECTS score may influence who benefits from receiving tenecteplase before thrombectomy — with a potential signal of benefit for those with lower scores and possible harm for those with higher scores. However, because this was an exploratory analysis performed after the original trial was completed, the authors caution that these findings should not change clinical practice until confirmed by prospective randomized trials designed specifically to test this question.
Huang X, Xu J, Saver J, Xu H, Yuan G, Kong Z, et al.. (2026). Effect of Baseline ASPECTS on Tenecteplase Efficacy Before Thrombectomy in Acute Large-Vessel Occlusion Stroke: A Post Hoc Analysis of the BRIDGE-TNK Randomized Trial.. Neurology. https://doi.org/10.1212/WNL.0000000000218467