Evaluating Intra-Arterial Tenecteplase for Stroke: Insights From the ANGEL-TNK Trial: Xiaochuan Huo, MD, PhD

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"We found that if patients are highly selected and if the injection technique is performed with the right positioning and at the right speed, they could benefit from this approach."

Intra-arterial tenecteplase has emerged as a potential adjunctive therapy for patients with acute ischemic stroke undergoing endovascular treatment. Unlike standard intravenous thrombolysis, which is administered systemically, intra-arterial delivery allows for targeted thrombolysis at the site of occlusion, potentially improving distal reperfusion and clinical outcomes. However, its efficacy, safety, and optimal use remain areas of ongoing investigation. Recent studies, including the ANGEL-TNK trial (NCT05624190), have sought to evaluate whether intra-arterial tenecteplase can enhance functional recovery without increasing the risk of complications.

Conducted in China, the ANGEL-TNK trial tested the efficacy and safety of intra-arterial tenecteplase following successful endovascular therapy for acute anterior circulation large vessel occlusion. Patients who presented between 4.5 to 24 hours after last being well and achieved successful recanalization were randomized in a 1:1 ratio to receive either intra-arterial tenecteplase or standard medical management. The primary outcome was a 90-day excellent functional outcome, defined as a modified Rankin Scale (mRS) score of 0 to 1, with additional secondary outcomes assessing mRS shifts, mortality, and intracranial hemorrhage. The primary safety end point was symptomatic intracranial hemorrhage in 48 hours.

Among the 255 patients enrolled, 127 received intra-arterial tenecteplase, while 129 underwent standard medical management. Presented at the 2025 International Stroke Conference (ISC), held February 5-7, in Los Angeles, California, the intra-arterial tenecteplase group demonstrated a significantly higher proportion of patients achieving an excellent functional outcome at 90 days compared with the standard treatment group (40.5% vs. 26.4%; relative rate 1.44; 95% CI, 1.06–1.95; P = 0.02). Mortality rates at 90 days were comparable between groups (21.4% vs. 21.7%; P = 0.39), and the incidence of symptomatic intracranial hemorrhage in 48 hours did not significantly differ (5.6% vs. 6.2%; P = 0.92). These findings suggest that intra-arterial tenecteplase following thrombectomy may improve functional outcomes without increasing the risk of symptomatic hemorrhage.^1,2

At ISC 2025, lead author of the study Xiaochuan Huo, MD, PhD, director of the Neurological Disease Center at Beijing Anzhen Hospital, sat down with NeurologyLive^® to discuss the broader implications of these findings. He talked about the key questions that remain regarding how intra-arterial tenecteplase compares with standard intravenous thrombolysis in terms of safety and efficacy, particularly in different patient populations. Huo highlighted the need to refine patient selection criteria to improve the generalizability of intra-arterial thrombolysis in stroke care. Additionally, he suggested that future research should focus on optimizing the dosage and delivery technique of intra-arterial tenecteplase to maximize benefits and minimize risks. As ongoing and planned trials continue to explore these aspects, Huo explained that the results of the ANGEL-TNK study provide a strong foundation for further investigation into this evolving treatment approach.

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REFERENCES
1. Huo et al. Intra-arterial Tenecteplase thrombolysis for acute LVO after successful mechanical thrombectomy recanalization (ANGEL-TNK) -- A Multicenter, Prospective, Randomized, Open-label, Blinded End-point Trial. Presented at: International Stroke Conference; February 5-7, 2025; LB38.
2. Removing large brain artery clot, chased with clot-buster shot may improve stroke outcomes. News Release. American Stroke Association. Published February 7, 2025. Accessed February 7, 2025. https://newsroom.heart.org/news/removing-large-brain-artery-clot-chased-with-clot-buster-shot-may-improve-stroke-outcomes