UMEM Educational Pearls

Background:

Several trials have explored the use of IV thrombolysis before endovascular thrombectomy (EVT) in ischemic stroke patients, and a pooled analysis from these trials showed no significant difference in efficacy between intravenous thrombolysis plus EVT compared to EVT alone. However, only 2.2% of patients in the trials included in this pooled analysis received tenecteplase (TNK), with the vast majority of patients receiving alteplase. (1) While a 2018 trial showed improved early reperfusion and 90-day outcomes with TNK compared to alteplase before EVT, a recent target trial emulation analysis indicated no added benefit with TNK plus EVT over EVT alone. (2-3) Lack of comparison between TNK plus EVT versus EVT alone and small sample sizes of prior trials led to the design of the BRIDGE-TNK trial, which directly compared TNK plus EVT versus EVT alone in acute ischemic stroke. (4)

Study design:

This multi-center, randomized, open-label trial conducted at 39 hospitals in China included patients with large-vessel occlusion (LVO) of the internal carotid, middle cerebral or basilar artery on CTA or MRA imaging who presented within 4.5 hours of their last known well time, and were eligible to undergo intravenous thrombolysis and EVT. 

Exclusion criteria were intracranial hemorrhage on CT or MRI imaging, rapidly improving symptoms at the discretion of the investigator, pre-stroke modified Rankin scale (mRS) of > 4, contraindication to imaging with contrast agents, patients who needed interhospital transfer before thrombectomy, any terminal illness such that the patient would not be expected to survive more than 1 year, any condition that could impost hazards to the patient if study therapy is initiated in the judgement of the investigator, hypodensity in >1/3 of middle cerebral artery or basilar artery territory on non-contrast CT, and pregnant women.

The primary outcome was functional independence at 90 days, defined as an mRS score of 0 to 2.

Patient Population:

Baseline characteristics were well matched between treatment arms:

• Median age: 70 for both groups
• Prestroke mRS was 0 for approximately 95% of patients enrolled in both groups
• Median NIH Stroke Score: 16 for both groups
• Median time from last known well to randomization: 159.3 minutes in the TNK plus EVT group vs. 167.6 minutes in the EVT group
• Median time from randomization to thrombolysis: 6 minutes for the TNK group
• Median time from randomization to thrombectomy puncture: 28.2 minutes in the TNK plus EVT group vs. 24.4 minutes in the EVT group 
• Median time from thrombectomy puncture to repurfusion: 55.0 minutes in the TNK plus EVT group vs. 64.0 minutes in the EVT group

Results:

Primary outcome: 

• mRS 0-2 at 90 days was achieved in 52.9% of patients receiving TNK plus EVT versus 44.1% of patient receiving EVT alone. (Risk ratio 1.18, 95% confidence interval: 1.01-1.39)

Secondary outcomes: 

• mRS 0-1 at 90 days: 
  • 34.9% of patients receiving TNK plus EVT versus 27.9% of patients receiving EVT alone. (Risk ratio 1.24, 95% confidence interval: 0.98-1.57)
• Successful reperfusion before thrombectomy: 
  • 6.1% of patients receiving TNK plus EVT versus 1.1% of patient receiving EVT alone. (Risk ratio 5.19, 95% confidence interval: 1.51-17.84)
• Successful reperfusion after thrombectomy: 
  • 91.4% of patients receiving TNK plus EVT versus 94.1% of patient receiving EVT alone. (Risk ratio 0.97, 95% confidence interval: 0.92-1.02)
• Symptomatic intracranial hemorrhage within 48 hours: 
  • 8.5% of patients receiving TNK plus EVT versus 6.7% of patient receiving EVT alone. (Risk ratio 1.35, 95% confidence interval: 0.74-2.44)
• Death within 90 days: 
  • 22.3% of patients receiving TNK plus EVT versus 19.9% of patient receiving EVT alone. (Hazard ratio: 1.17, 95% confidence interval: 0.81-1.69)

Study Limitations:

• Study had an open-label design (though outcomes were adjudicated by an independent committee unaware of treatment assignments)
• Exclusion of patients who required transfer for EVT limits generalizability to patients initially evaluated at hospitals that are not thrombectomy capable
• The observed absolute difference in functional independence of 90 days was 8.8%, which fell below the prespecified assumption of 13% that was used to calculate the sample size

Key Takeaways:

While rates of symptomatic intracranial hemorrhage and mortality were higher in the TNK + EVT group, neither of these outcomes met statistical significance and bridging with TNK prior to EVT led to increased rates of functional independence at 90 days compared to EVT alone. The findings of this study reinforce current guideline recommendations for not skipping intravenous thrombolysis prior to thrombectomy for LVO stroke.

References

1. Majoie CB, Cavalcante F, Gralla J, et al. Value of intravenous thrombolysis in endovascular treatment for large-vessel anterior circulation stroke: individual participant data meta-analysis of six randomised trials. Lancet 2023;402:965-74

2. Campbell BCV, Mitchell PJ, Churilov L, et al. Tenecteplase versus alteplase before thrombectomy for ischemic stroke. N Engl J Med 2018;378:1573-82

3. Altersberger VL, Kaesmacher J, Churilov L, et al. Bridging thrombolysis with tenecteplase versus endovascular thrombectomy alone for large-vessel anterior circulation stroke: a target trial emulation analysis. J Neurol Neurosurg Psychiatry. 2025;96(8):775-783. Published 2025 Jul 16. Doi:10.1136/jnnp-2024-335325 

4. Qiu Z, Li F, Sang H, et al. Intravenous Tenecteplase before Thrombectomy in Stroke. N Engl J Med. 2025;393(2):139-150. doi:10.1056/NEJMoa2503867d