World Stroke Organization The Paper of The Month – May
30 May 2025Tenecteplase Before Thrombectomy - A New Bridge or Just a Detour?
Tenecteplase Before Thrombectomy — A New Bridge or Just a Detour?
Prof. Octavio Marques Pontes-Neto, MD, PhD – Editor-in-Chief, World Stroke Academy
This article is a commentary on the following: Intravenous Tenecteplase before Thrombectomy in Stroke, The New England Journal of Medicine, DOI: 10.1056/NEJMoa2503867, Copyright © 2025 Massachusetts Medical Society, https://www.nejm.org/doi/full/10.1056/NEJMoa2503867
Commentary:
The BRIDGE-TNK trial, recently published in The New England Journal of Medicine, provides new and much-anticipated evidence on the role of intravenous tenecteplase prior to endovascular thrombectomy (EVT) for acute ischemic stroke due to large-vessel occlusion (LVO). The findings offer additional evidence in favor of tenecteplase for acute stroke and raise cautious optimism about the benefit of bridging therapy in the evolving landscape of acute stroke reperfusion therapy.
In this multicenter, open-label randomized trial conducted across 39 centers in China, 550 patients with LVO stroke eligible for thrombolysis within 4.5 hours of symptom onset were assigned to receive either tenecteplase plus EVT or EVT alone. The results were modest but statistically significant: functional independence at 90 days (mRS 0–2) was achieved in 52.9% of the tenecteplase-EVT group versus 44.1% in the EVT-alone group (adjusted RR, 1.18; 95% CI, 1.01–1.39; P = 0.04). This translates to a number needed to treat (NNT) of approximately 11—12, an effect size comparable to early bridging alteplase trials, though smaller than that seen in early EVT trials. The trial also revealed an increased rate of reperfusion prior to thrombectomy (6.1% vs. 1.1%), but no significant differences in successful reperfusion post-EVT or in first-pass effect. Symptomatic intracerebral hemorrhage (sICH) occurred more frequently in the tenecteplase arm (8.5% vs. 6.7%), and mortality was slightly higher (22.3% vs. 19.9%), although neither reached statistical significance. The safety profile, while acceptable, underscores the fine balance clinicians must weigh between early clot dissolution and the potential for bleeding complications.
Previous randomized trials evaluating intravenous alteplase prior to EVT have produced mixed results, with meta-analyses suggesting non-inferiority of direct EVT strategies. However, most studies involved alteplase, not tenecteplase. The BRIDGE-TNK trial stands out as the largest RCT to date directly comparing tenecteplase bridging to EVT alone. While earlier studies like ACT and EXTEND-IA TNK demonstrated promising results for tenecteplase in selected populations, this trial broadens the scope to real-world practice, albeit within the Chinese population, with its higher proportion of large artery atherosclerotic stroke.
Given their relevance and novelty, the findings may require additional validation. The absolute benefit was modest, secondary outcomes were largely neutral, and the open-label design may have introduced bias, despite blinded outcome assessment. Notably, patients requiring interhospital transfer were excluded, limiting generalizability in prehospital triage and mobile stroke unit contexts. Moreover, the trial provides no insight into the efficacy of tenecteplase beyond the 4.5-hour window or in wake-up strokes. The BRIDGE-TNK results will inevitably fuel debate about the optimal reperfusion strategy.
Ongoing trials such as RESILIENT DIRECT-TNK, a placebo-controlled, double-blind randomized clinical trial in Brazil may help confirm or refute these findings in more diverse populations. Until then, clinicians may consider tenecteplase bridging as a viable option where rapid EVT access is guaranteed, and particularly in systems where tenecteplase is available and operationally advantageous.
The BRIDGE-TNK trial adds another piece to the complex puzzle of stroke reperfusion therapy. While it does reinforce tenecteplase as a promising pre-thrombectomy solution, it revives the conversation about personalized, context-specific stroke care. Further validation and meta-analytical integration with ongoing studies will be essential for a clear recommendation to clinical practice.
References:
- Qiu Z, Li F, Sang H, Yuan G, Xie D, Zhou K, Li M, Meng Z, Kong Z, Ruan Z, Li C, Yang G, Wu J, Long C, Yang B, Hu H, Li Y, Luo J, Shi Z, Huang X, Jiang S, Yi T, Zeng G, Liu J, Luo X, Liu S, Chang M, Wu Y, Tang Y, Tian Z, Yan Z, Zhao H, Peng Y, Dai H, Zhou P, Li H, Liu W, Song D, Lei B, Xia Z, Tan X, Zhao M, Feng X, Cai L, Li Q, Wu Y, Jiang B, Tian Y, Li L, Jiang L, Long X, You F, Tao J, Zhou J, Wu D, Zheng C, Yin C, Wang D, Lu M, Albers GW, Nogueira RG, Campbell BCV, Nguyen TN, Saver JL, Zi W, Yang Q; BRIDGE-TNK Trial Investigators. Intravenous Tenecteplase before Thrombectomy in Stroke. N Engl J Med. 2025 May 21. doi: 10.1056/NEJMoa2503867. Epub ahead of print. PMID: 40396577.
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