Tenecteplase Benefit Before Thrombectomy Varies by Stroke Cause, Study Shows

A secondary analysis of the BRIDGE-TNK trial (NCT04733742) found that intravenous tenecteplase given before endovascular thrombectomy (EVT) improved 90-day functional outcomes in patients with cardioembolic (CE) stroke but not in those with large artery atherosclerosis (LAA), despite similar rates of symptomatic hemorrhage in both subgroups. The analysis was presented by Zhongfan Ruan, MD, of the department of neurology at the Multiomics Research Center for Brain Disorders, at the World Stroke Congress (WSC 2026), held October 21-23, 2026, in Seoul, Republic of Korea.¹

The analysis covered 502 of the 550 patients randomized in BRIDGE-TNK who had a determined etiology of either LAA (167 patients) or CE (335 patients). Patients were eligible for the parent trial if they presented within 4.5 hours of last known well and were candidates for intravenous thrombolysis; they were randomized to tenecteplase followed by EVT or to EVT alone.^1,2

Overall, the 90-day rate of functional independence (modified Rankin Scale [mRS] score of 0-2) with tenecteplase plus EVT versus EVT alone was 46.3% versus 49.4% among patients with LAA (relative risk [RR], 0.99; 95% CI, 0.72-1.36) and 55.8% versus 40.5% among patients with CE (RR, 1.28; 95% CI, 1.04-1.58). The treatment-by-etiology interaction was not significant for functional independence overall (P =.13), but was significant for the full mRS distribution (P =.04) and for the mRS 0-3 rate (P =.02).

Symptomatic intracranial hemorrhage within 48 hours did not differ significantly between treatment groups in either subgroup (LAA, 7.1% with tenecteplase vs 5.1% with EVT alone; CE, 6.3% vs 8.3%). Ninety-day mortality differed significantly by etiology (treatment-by-etiology interaction, P =.04). Among patients with CE, mortality was similar with tenecteplase (23.9%) and EVT alone (18.0%; hazard ratio [HR], 0.86; 95% CI, 0.53-1.38).

READ MORE: Endovascular Therapy Benefit in Distal Vessel Stroke Tied to Severity, Not IVT Status

Among patients with LAA, mortality was higher with tenecteplase (HR, 2.08; 95% CI, 1.03-4.22), giving rates of 14.1% and 29.3% between the 2 arms; unlike the functional outcome and hemorrhage figures elsewhere in the abstract, the arm order for this specific pair of rates was not stated explicitly.¹

The investigators concluded that stroke etiology appeared to modify the effect of pre-thrombectomy tenecteplase in large vessel occlusion treated within 4.5 hours. Patients with CE stroke appeared more likely to derive functional benefit from tenecteplase, while patients with LAA did not, despite higher rates of reperfusion before thrombectomy in the tenecteplase group.

The BRIDGE-TNK trial and its primary results

BRIDGE-TNK was an investigator-initiated, multicenter, randomized, open-label trial conducted at 40 thrombectomy-capable centers in China between May 9, 2022, and September 8, 2024. Patients with acute large vessel occlusion stroke who were eligible for intravenous thrombolysis within 4.5 hours of last known well were randomized 1:1 to tenecteplase (0.25 mg/kg, maximum 25 mg) followed by EVT or to EVT alone, with a primary outcome of functional independence (mRS score 0-2) at 90 days. The study was sponsored in part by CSPC Recomgen Pharmaceutical, which supplied the tenecteplase.²

In the trial's primary results, published in May 2025, 550 patients were randomized (278 to tenecteplase plus EVT, 272 to EVT alone). Functional independence at 90 days was achieved by 52.9% of patients who received tenecteplase before EVT versus 44.1% of those who received EVT alone (RR, 1.20; 95% CI, 1.01-1.43; P =.04), meeting the trial's primary endpoint. Symptomatic intracranial hemorrhage within 48 hours occurred in 8.5% of the tenecteplase group versus 6.7% of the EVT-alone group, and 90-day mortality was 22.3% versus 19.9%; neither difference reached statistical significance.²

For more WSC 2026 coverage, click here.

REFERENCES
1. Ruan Z, et al. Effect of stroke etiology on outcomes of tenecteplase plus thrombectomy versus thrombectomy alone: a secondary analysis of the BRIDGE-TNK trial. Presented at: World Stroke Congress 2026 (WSC 2026); October 21-23, 2026; Seoul, Republic of Korea.
2. 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/NEJMoa2503867