Quick Facts
- Stroke etiology may influence the benefit of bridging tenecteplase before EVT. Patients with cardioembolic LVO appeared more likely to benefit, with functional independence achieved in 55.8% vs 40.5% with EVT alone.
- No functional benefit was observed in LAA stroke. Functional independence was similar with tenecteplase plus EVT versus EVT alone (46.3% vs 49.4%), despite greater pre-EVT reperfusion.
- Symptomatic ICH rates were similar between treatment groups. No significant differences were observed in either the LAA or cardioembolic subgroups, although the subgroup estimates had wide confidence intervals.
- The higher mortality observed in LAA patients warrants further investigation. Ninety-day mortality was 29.3% with tenecteplase plus EVT vs 14.1% with EVT alone, suggesting stroke mechanism may be important when considering bridging thrombolysis.
The Original BRIDGE-TNK Trial
The BRIDGE-TNK trial, conducted in China, was a multicenter, randomized controlled open-label trial contrasting intravenous tenecteplase treatment on top of endovascular treatment with endovascular treatment alone among patients with large vessel occlusion (LVO). Patients were eligible for enrollment if they had undergone an acute ischemic stroke who was eligible for intravenous thrombolysis treatment within 4.5 hours of time last known well, among other criteria. Patients were excluded if they had intracranial hemorrhage on baseline scans or arterial tortuosity, among other criteria.2,3
The primary endpoint of BRIDGE-TNK was the proportion of patients functionally independent at 90 days, defined as having a modified Rankin Scale (mRS) score of 0-2. Secondary endpoints included mRS score at 90 days, the proportion of patients non-disabled or who return to pre-morbid mRS score at 90 days, and the proportion of patients ambulatory or bodily needs-capable or better at 90 days, among others.3
A total of 278 patients were assigned to the tenecteplase-thrombectomy arm, and 272 were assigned to thrombectomy alone. After 90 days, functional independence was observed in 147 patients in the tenecteplase-thrombectomy arm (52.9%) and in 120 patients in the thrombectomy arm (44.1%) (unadjusted risk ratio [RR], 1.2; 95% CI, 1.01-1.43; P = .04). Additionally, 6.1% of the patients in the tenecteplase-thrombectomy arm and 1.1% in the thrombectomy arm had successful reperfusion before thrombectomy, while 91.4% and 94.1%, respectively, had successful reperfusion afterward.2
Accounting for Stroke Etiologies
In the present analysis, Ruan and colleagues included 502 patients from BRIDGE-TNK, stratifying them by etiology in addition to their assigned treatment arm. The team aimed to determine whether large artery atherosclerosis (LAA) and CE modified the outcomes of tenecteplase plus thrombectomy within 4.5 hours of treatment. The primary outcome was the same, while the safety outcome included 48-hour intracranial hemorrhage and 90-day mortality.1
Of 550 included patients, 167 had LAA (32.6%) and 335 had CE (65.4%). The 90-day functional independence rate for tenecteplase-thrombectomy was 46.3% in patients with LAA, while the thrombectomy arm saw a rate of 49.4% (RR, 0.99; 95% CI, 0.72-1.36). Patients with CE saw a rate of 55.8% with tenecteplase and thrombectomy, versus 40.5% with thrombectomy alone (RR, 1.28; 95% CI, 1.04-1.58). Treatment-by-etiology interactions were nonsignificant for functional independence, but were significant for both mRS distribution and mRS 0-3 rate.1
Symptomatic intracranial hemorrhage did not differ between treatments in either subgroup (LAA, 7.1% vs 5.1%; RR, 1.04; 95% CI, 0.3-3.62; CE, 6.3% vs 8.3%; RR, 1.48; 95% CI, 0.66-3.34). 90-day mortality was greater with tenecteplase in patients with LAA (14.1% vs 29.3%; HR, 2.08; 95% CI, 1.03-4.22), but similar in patients with CE (23.9% vs 18%; HR, 0.86; 95% CI, 0.53-1.38), with significant interaction (P = .04).1
“In acute LVO within 4.5 hours, stroke etiology appeared to modify pre-EVT tenecteplase’s effect,” Ruan and colleagues wrote. “CE patients seemed more likely to derive functional benefit, whereas LAA patients did not despite higher pre-thrombectomy reperfusion.”1
References
Ruan Z. Effect of Stroke Etiology on Outcomes of Tenecteplase Plus Thrombectomy Versus Thrombectomy Alone: A Secondary Analysis of the BRIDGE-TNK Trial. Abstract presented at the World Stroke Congress (WSC) 2026, Seoul, Republic of South Korea. October 21-23, 2026.
Qiu Z, Li F, Sang H, et al. Intravenous tenecteplase before thrombectomy in stroke. New England Journal of Medicine. 2025;393(2):139-150. doi:10.1056/nejmoa2503867
Zhongming Qiu, Xinqiao Hospital of Chongqing. Endovascular Treatment With Versus Without Intravenous rhTNK-tPA in Stroke (BRIDGE-TNK). ClinicalTrials.gov Identifier: NCT04733742. Updated April 3, 2025. Accessed October 20, 2026. https://clinicaltrials.gov/study/NCT04733742?term=NCT04733742&rank=1
