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ABSTRACT & COMMENTARY
Use of IV Tenecteplase Prior to Thrombectomy in Stroke
July 1, 2025 5 minutes read
By Alan Z. Segal, MD
Synopsis: In patients with acute ischemic stroke arriving at a thrombectomy-ready hospital within 4.5 hours of stroke onset, the combination of treatment with intravenous tenecteplase followed by mechanical thrombectomy resulted in superior outcomes compared to thrombectomy alone.
Source: Qiu Z, Li F, Sang H, et al; BRIDGE-TNK Trial Investigators. Intravenous tenecteplase before thrombectomy in stroke. N Engl J Med. 2025; May 21. doi: 10.1056/NEJMoa2503867. [Online ahead of print].
Mechanical thrombectomy (MT) is the standard of care for patients presenting with acute ischemic stroke (AIS) caused by large vessel occlusion (LVO). However, a thornier question has been whether intravenous thrombolysis (IVT) prior to MT is of added benefit as compared to “skipping” IVT in favor of MT alone. Arguments in favor of IVT + MT include the possibility that IVT would enhance the efficacy of MT by treating macroscopic distal clots or preserving flow at the level of the microcirculation. There also is the possibility that IVT could produce recanalization and obviate the need for MT altogether. Arguments against the use of IVT + MT include the possibility that combination therapy could increase hemorrhage rates and that the use of a non-effective therapy (IVT) could delay the use of definitive therapy (MT).
These questions were extensively explored in six large, randomized trials. Among them are DIRECT-MT, SKIP, DEVT, and MR CLEAN — NO IV. These studies provided conflicting results and generally used noninferiority methodology rather than attempting to prove one strategy as better than the other. A pooled analysis of all available data, with a total of 1,160 patients on combined treatment and 1,153 patients treated with MT alone, showed that there was no significant difference between these two strategies, but the trend favored the MT-only group.1
Over the past few years, IVT has undergone a major pharmacological shift, with the replacement of alteplase (tPA) by tenecteplase (TNK) — a second-generation recombinant plasminogen activator. The transition from tPA to TNK began as early as 2002, with guidelines recommending its use in 2023, but only in March 2025 did the U.S. Food and Drug Administration (FDA) approve TNK for AIS. Among the multiple advantages of TNK over tPA are increased clot (fibrin) specificity, single-dose administration (bolus vs. prolonged infusion), and improved vascular recanalization with a lowered risk of hemorrhage.
Although IVT has not shown convincing benefit prior to endovascular thrombectomy, a head-to-head comparison between tPA and TNK (EXTEND IA TNK) showed a significant superiority for TNK, with a 22% recanalization rate in the TNK arm compared to 10% with tPA. Functional outcomes also were more favorable.2 Given this TNK superiority, the current study (BRIDGE-TNK) seeks to answer the previously negative “skip” question by exploring whether TNK + MT would be superior to MT alone in the treatment of AIS caused by LVO. Of note, TNK was used sparingly in the “skip” trials, which almost exclusively used tPA (97.8% of patients).
The BRIDGE-TNK trial studied 278 patients treated with TNK + MT compared to 272 patients treated with MT alone. Functional independence at 90 days was achieved in 52.9% of combination treatment patients compared to 44.1% of patients treated with only MT. Successful reperfusion prior to MT was reported in 6.1% of combination treatment patients compared to 1.1% of patients without TNK prior to MT. These rates were significantly lower than in the EXTEND IA TNK study. Among many study differences, IVT in the EXTEND IA TNK study was given more time to work, with an average of 43 minutes between IVT and MT, compared to only 16 minutes in BRIDGE-TNK. Unlike intravenous tPA, which requires a one-hour infusion, a TNK bolus can be rapidly followed by transport to the angiography suite for MT.
Reperfusion rates post-MT in BRIDGE-TNK were greater than 90%, consistent with the expected efficacy of MT using modern thrombectomy techniques, such as next-generation stent retrievers (Solitaire X and TREVO NXT) or clot aspirators (Penumbra). Unexpectedly, MT alone produced marginally better reperfusion results, 94% compared to 91% with combination therapy. Combination therapy also produced increased hemorrhage rates (8.5% combination vs. 6.7% for MT alone), which translated into increased mortality with IVT + MT (23.3% compared to 19.9% with MT alone). However, these small increases in poor outcomes did not wash out the central conclusion of BRIDGE-TNK, which was that combination therapy produced more favorable functional results overall compared to MT alone.
Commentary
Although the question of skipping IVT prior to MT has been the subject of extensive study, it is important to recognize that this applies only to a small fraction of AIS patients (those presenting < 4.5 hours) and only those who present to a comprehensive or thrombectomy-ready stroke center where both therapies can be offered in rapid succession. These investigations are not applicable to the common scenario in which a patient is brought to a primary stroke center, given IVT, and then transferred for definitive MT, which often can occur only after significant travel delays.
Even if narrowly applicable, this study is important because it supports the fact that the advantages of TNK over tPA may extend well beyond its basic use for IVT in hyperacute AIS. These data provide encouragement that TNK may prove useful in situations where tPA previously has shown no benefit. This would include IVT for minor, nondisabling stroke.
Existing studies (PRISMS and ARTEMIS) showed no benefit of tPA over medical therapy but begs the question of whether TNK would have yielded positive results. Similarly, TNK may allow for IVT beyond 4.5 hours in carefully selected patients. The EXTEND and WAKE-UP trials have established that IV tPA can be beneficial in the 4.5- to nine-hour window when MRI shows a mismatch between diffusion-weighted imaging and FLAIR sequences. TNK has shown advantages over medical therapy in the 4.5- to 24-hour time window when computed tomography (CT) perfusion shows a favorable profile of salvageable tissue (TRACE-III and TIMELESS). However, the use of TNK beyond 4.5 hours using CT scan alone has failed to show favorable results. This is consistent with multiple studies of IV tPA beyond 4.5 hours showing no benefit without the aid of advanced imaging to optimize tissue-based patient selection.
Alan Z. Segal, MD, is Associate Professor of Neurology, Weill Cornell Medicine.
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(10406):965-974.
2. Campbell BCV, Mitchell PJ, Churilov L, et al. Tenecteplase versus alteplase before thrombectomy for ischemic stroke. N Engl J Med. 2018;378(17):1573-1582.
In patients with acute ischemic stroke arriving at a thrombectomy-ready hospital within 4.5 hours of stroke onset, the combination of treatment with intravenous tenecteplase followed by mechanical thrombectomy resulted in superior outcomes compared to thrombectomy alone.
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