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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

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Year of Publication: 2026

Authors: Huang X, Xu J, Saver JL, ..., Li Z

Journal: Neurology

Citation: Neurology 2026;107:e218467. doi:10.1212/WNL.0000000000218467

Link: https://doi.org/10.1212/WNL.0000000000218467

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%; HR 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

Baseline Characteristics

CharacteristicASPECTS <8 - Tenecteplase + Thrombectomy (n=113)ASPECTS <8 - Thrombectomy alone (n=128)ASPECTS 8-10 - Tenecteplase + Thrombectomy (n=165)ASPECTS 8-10 - Thrombectomy alone (n=144)
Age median (IQR) years70 (61-79)69 (62-75)70 (60-77)70 (63-77)
Male %55.857.059.459.7
Hypertension %60.271.962.459.7
Diabetes %23.924.218.218.8
Hyperlipidemia %17.728.920.020.8
Atrial fibrillation %45.134.430.336.1
Prior ischemic stroke %22.119.516.417.4
Coronary heart disease %20.427.321.226.4
Prestroke mRS >1 %03.12.40.7
Baseline NIHSS median (IQR)18 (12-22)17 (12-20)15 (12-20)15 (11-20)
Baseline SBP median (IQR) mmHg144 (130-160)150 (132-170)143 (130-166)148 (126-168)
Baseline glucose median (IQR) mmol/L7.5 (6.1-9.7)7.6 (6.4-9.4)7.1 (6.0-8.8)7.0 (5.9-8.5)
CT-based ASPECTS %84.184.490.392.4
MR-based ASPECTS %15.915.69.77.6

Arms

FieldTenecteplase plus ThrombectomyControl
N278272
InterventionIntravenous tenecteplase followed by endovascular thrombectomyEndovascular thrombectomy without IV thrombolysis
DurationWithin 4.5 hours of last known wellWithin 4.5 hours of last known well

Outcomes

OutcomeTypeControlInterventionHR / OR / RRP-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)PrimaryASPECTS <8: 25.0% (32/128); ASPECTS 8-10: 61.1%ASPECTS <8: 41.6% (47/113); ASPECTS 8-10: 60.6%1.67ASPECTS <8: 0.003; ASPECTS 8-10: 0.92; p interaction = 0.007
Freedom from disability (mRS 0-1) at 90 daysSecondarySignificant effect modification by ASPECTS stratification (p interaction = 0.01)
Ambulation and independent self-care (mRS 0-3) at 90 daysSecondarySignificant effect modification by ASPECTS stratification (p interaction = 0.04)
Favorable shift in overall mRS distribution at 90 daysSecondaryFavorable shift only in ASPECTS <8, not in ASPECTS 8-10 (p interaction = 0.01)
Successful reperfusion before thrombectomySecondaryASPECTS <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); sICH data unavailable for 10 patients (6 in ASPECTS <8, 4 in ASPECTS >=8)SafetyASPECTS <8: 11 (10.0%) vs 14 (11.2%); aRR 0.92, 95% CI 0.42-1.99 (denominators reduced by 6 missing patients in ASPECTS <8 group) · ASPECTS 8-10: 12 (7.5%) vs 4 (2.8%); aRR 2.87, 95% CI 0.94-8.78 (denominators reduced by 4 missing patients in ASPECTS >=8 group) · P interaction: 0.11
Any ICH on imaging within 48 hoursSafetyNo significant increased risk with tenecteplase in either ASPECTS subgroup (p interaction = 0.53)
90-day mortalitySafetyASPECTS <8: 33 (29.2%) vs 39 (30.5%) (HR 0.86, 95% CI 0.54-1.38) · ASPECTS 8-10: 29 (17.6%) vs 15 (10.4%); HR 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

Funding

Anhui Province Clinical Medicine Transformation Special Project in China (No. 202427b10020048); Key Project of the Department of Education of Anhui Province (No. 2025AHGXZK20227); Research Funds of Centre for Leading Medicine and Advanced Technologies of IHM in China (No. 2023IHM01053).

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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