BRIDGE-TNK ASPECTS
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
Clinical Question
Does baseline ASPECTS modify the efficacy and safety of IV tenecteplase before endovascular thrombectomy in acute large-vessel occlusion stroke?
Bottom Line
In this exploratory post hoc analysis of BRIDGE-TNK, IV tenecteplase before thrombectomy was associated with improved 90-day functional independence in patients with unfavorable ASPECTS (<8), but showed no benefit and a possible safety concern (numerically higher mortality) in patients with favorable ASPECTS (8-10). Prospective confirmation is required before practice change.
Major Points
- Post hoc subgroup analysis of BRIDGE-TNK stratified by baseline ASPECTS (<8 vs 8-10)
- Among 550 patients, 241 (43.8%) had ASPECTS <8 and 309 had ASPECTS 8-10
- In ASPECTS <8: significantly higher 90-day functional independence with tenecteplase + thrombectomy (41.6% vs 25.0%; aRR 1.67, 95% CI 1.18-2.35)
- In ASPECTS 8-10: no functional benefit (60.6% vs 61.1%; aRR 0.99, 95% CI 0.84-1.17)
- Significant treatment-by-ASPECTS interaction for functional independence (p interaction = 0.007)
- Continuous analysis showed crossover of treatment effect at ASPECTS 9
- sICH rates did not differ significantly in either ASPECTS subgroup (p interaction = 0.11)
- 90-day mortality numerically higher with tenecteplase in ASPECTS 8-10 subgroup (17.6% vs 10.4%; aRR 1.89, 95% CI 0.99-3.61; p interaction = 0.04)
- ASPECTS cutoff of <8 vs 8-10 was chosen post hoc in a data-driven manner (not prespecified)
Design
Study Type: Post hoc subgroup analysis of a multicenter, investigator-initiated, open-label randomized controlled trial
Randomization: 1
Blinding: Open-label (imaging core lab blinded to clinical characteristics and outcomes)
Allocation: Randomized
Enrollment Period: May 2022 to September 2024
Follow-up Duration: 90 days
Centers: 39
Countries: China
Sample Size: 554
Analyzed: 550
Analysis: Modified Poisson regression for binary outcomes adjusted for age, baseline NIHSS, ASPECTS, occlusion site, and time from last known well to randomization. Proportional odds logistic regression for mRS shift. Cox proportional hazards for mortality. Treatment-by-ASPECTS interaction term used to examine effect modification. Propensity score matching for sensitivity analysis (1:1 nearest-neighbor, caliper 0.2).
Registration: ClinicalTrials.gov NCT04733742
Inclusion Criteria
- Acute large-vessel occlusion stroke
- Eligible for IV thrombolysis
- Within 4.5 hours of last known well
- Scheduled for endovascular thrombectomy
Arms
| Field | Tenecteplase plus Thrombectomy | Control |
|---|---|---|
| N | 278 | 272 |
| Intervention | Intravenous tenecteplase followed by endovascular thrombectomy | Endovascular thrombectomy without IV thrombolysis |
| Duration | Within 4.5 hours of last known well | Within 4.5 hours of last known well |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| Proportion of patients achieving functional independence (modified Rankin Scale score of 0-2) at 90 days, stratified by baseline ASPECTS (<8 vs 8-10) | Primary | ASPECTS <8: 25.0% (32/128); ASPECTS 8-10: 61.1% | ASPECTS <8: 41.6% (47/113); ASPECTS 8-10: 60.6% | 1.67 | ASPECTS <8: 0.003; ASPECTS 8-10: 0.92; p interaction = 0.007 |
| Freedom from disability (mRS 0-1) at 90 days | Secondary | Significant effect modification by ASPECTS stratification (p interaction = 0.01) | |||
| Ambulation and independent self-care (mRS 0-3) at 90 days | Secondary | Significant effect modification by ASPECTS stratification (p interaction = 0.04) | |||
| Favorable shift in overall mRS distribution at 90 days | Secondary | Favorable shift only in ASPECTS <8, not in ASPECTS 8-10 (p interaction = 0.01) | |||
| Successful reperfusion before thrombectomy | Secondary | ASPECTS <8: 6.2% vs 1.6%; ASPECTS 8-10 (>=8): 6.1% vs 0.7%; p interaction = 0.52 (numerically higher with tenecteplase in both) | |||
| Symptomatic intracranial hemorrhage (sICH) within 48 hours (modified Heidelberg Bleeding Classification) | Safety | ASPECTS <8: 10.0% (11/113) vs 11.2% (14/128); aRR 0.92, 95% CI 0.42-1.99 · ASPECTS 8-10: 7.5% (12/165) vs 2.8% (4/144); aRR 2.87, 95% CI 0.94-8.78 · P interaction: 0.11 | |||
| Any ICH on imaging within 48 hours | Safety | No significant increased risk with tenecteplase in either ASPECTS subgroup (p interaction = 0.53) | |||
| 90-day mortality | Safety | ASPECTS <8: 29.2% vs 30.5% (comparable) · ASPECTS 8-10: 17.6% vs 10.4%; aRR 1.89, 95% CI 0.99-3.61 · P interaction: 0.04 | |||
Subgroup Analysis
Primary analysis was subgroup by baseline ASPECTS (<8 vs 8-10). Sensitivity analyses performed in patients with extensive ischemic core (ASPECTS 0-5) and in those with isolated anterior circulation large-vessel occlusion using only NCCT-based ASPECTS. Continuous ASPECTS analysis showed significant treatment-by-ASPECTS interaction for 90-day functional independence (p interaction = 0.03) with crossover at ASPECTS 9. No significant interaction for sICH risk as continuous variable (p interaction = 0.27), though crossover was observed at ASPECTS 5.
Criticisms
- Post hoc, exploratory analysis - not prespecified
- ASPECTS cutoff of <8 vs 8-10 was chosen in a data-driven manner (not prespecified)
- Open-label design of parent trial
- Conducted entirely in China - generalizability to other populations uncertain
- Numerically higher mortality with tenecteplase in ASPECTS 8-10 warrants caution
- Baseline imbalances between ASPECTS subgroups (higher NIHSS, more ICA occlusion, worse collaterals in ASPECTS <8)
- Sample size may be underpowered for safety outcomes and interactions
- Prospective confirmation in randomized trials required before practice change
Based on: BRIDGE-TNK ASPECTS (Neurology, 2026)
Authors: Huang X, Xu J, Saver JL, ..., Li Z
Citation: Neurology 2026;107:e218467. doi:10.1212/WNL.0000000000218467
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