While new data have provided solid evidence on tenecteplase’s benefits in non-large vessel occlusion (LVO) ischaemic stroke patients presenting within 24 hours from symptom onset, bridging intravenous thrombolysis (IVT)—usage of the drug shortly before a mechanical thrombectomy procedure—in late-window patients with proximal middle cerebral artery (MCA) or basilar artery occlusions does not appear to meaningfully improve clinical outcomes.
These insights were generated by the OPTION, ATTENTION LATE and TNK-PLUS randomised controlled trials (RCTs), each of which was presented for the first time at the 2026 International Stroke Conference (ISC; 4–6 February, New Orleans, USA).
“We are increasingly moving towards tenecteplase in our clinical practice—and, this year, the American Heart Association [AHA] came out with new guidelines that acknowledge tenecteplase as a clear alternative in the acute stroke time window of 4.5 hours,” said ISC co-chair Bijoy Menon (University of Calgary, Calgary, Canada), speaking with NeuroNews. “Now, our field is trying to understand how best to use it in various other scenarios.”
To this end, the three RCTs disclosed on the second day of ISC 2026—despite their shared focus on patients presenting in the later time window from 4.5–24 hours—all sought to answer slightly different questions on tenecteplase’s role in ischaemic stroke care, and ultimately revealed mixed degrees of clinical benefit.
“Our evidence builds up in steps,” Menon continued. “I think we will have a more cogent story in two or three years but, right now, we know that tenecteplase is the thrombolytic drug of choice in the early time window, period. We also now have increasing evidence showing that tenecteplase works in the late time window in patients with LVOs who are not candidates for thrombectomy, but that giving the drug very shortly before a thrombectomy may not have much benefit.”
OPTION trial data
The OPTION RCT—shared at ISC by Ran Mo on behalf of study principal investigator Junwei Hao (both Xuanwu Hospital Capital Medical University, Beijing, China) and colleagues—randomised a total of 570 patients with non-LVO acute ischaemic strokes and salvageable brain tissue across 48 centres in China. Patients presenting 4.5–24 hours from time last seen well received 0.25mg/kg of intravenous tenecteplase if allocated to the treatment arm or standard medical care if allocated to the control arm.
As per its primary endpoint, the trial observed a 43.6% rate of excellent functional outcomes (modified Rankin scale [mRS] 0–1) at 90 days with tenecteplase versus a 34.2% rate with standard care, giving rise to an unadjusted risk difference close to 10% and an adjusted risk ratio of 1.32 favouring the tenecteplase group (p=0.007). Mo’s presentation of this finding drew a round of applause from the ISC audience. However, while 90-day mortality rates were statistically similar between tenecteplase and standard care (5% vs 3.2%; risk ratio, 1.57; p=0.28) and systemic bleeding rates were identical at 0.7% in both groups, the incidence of symptomatic intracranial haemorrhage (sICH) within 36 hours was found to be higher with tenecteplase (2.8%) versus standard care (0%; p=0.004).
A comprehensive summary of these data has also been published in the Journal of the American Medical Association (JAMA). In addition to providing further detail on the trial’s secondary outcomes, the paper includes analyses of several different subgroups—all of which show that increased rates of 90-day mRS 0–1 with tenecteplase compared to standard care were sustained. The authors therefore conclude that “these results support extending the thrombolysis time window in this patient population”.
“This trial shows that, in those patients where you don’t have the option for thrombectomy, the drug seems to work and is safe,” Menon added. “That is quite reassuring, and it also lays the foundation for some other large trials that may conclusively prove the point and expand the treatment armamentarium for stroke patients.”
ATTENTION LATE and TNK-PLUS
Presenting data from the prospective ATTENTION LATE trial at ISC, Chunrong Tao (University of Science and Technology of China, Hefei, China) initially posited that posterior-circulation stroke cases were “underrepresented” in the TIMELESS RCT—one of the biggest research endeavours on late-window tenecteplase treatments to date, which ultimately saw the drug fail to improve clinical outcomes versus a placebo. As such, ATTENTION LATE enrolled a population of basilar artery occlusion stroke patients presenting 4.5–24 hours from symptom onset at a total of 40 Chinese sites. Some 332 of these patients were allocated to either 0.25mg/kg of intravenous tenecteplase prior to a thrombectomy procedure, or thrombectomy alone without IVT therapy. Tao detailed that overall treatment times were comparable across these groups, indicating that tenecteplase administration did not cause any meaningful delays.
However, the investigators found that there was no statistically significant difference in 90-day rates of functional independence (mRS 0–2) between the two study groups (rate ratio, 0.92), with more granular subgroup analyses also showing that bridging therapy with tenecteplase and direct thrombectomy produced similar clinical outcomes regardless of age, baseline National Institutes of Health stroke scale (NIHSS) score, specific occlusion location, or estimated time from symptom onset to randomisation. Furthermore, the two treatment approaches demonstrated parity in terms of secondary efficacy endpoints including 90-day mRS 0–1, 24-hour median NIHSS and quality-of-life scores as well as the trial’s major safety outcomes, such as 90-day mortality and 72-hour ICH—symptomatic or otherwise.
Tao concluded that these ATTENTION LATE data do not support the routine utilisation of bridging thrombolysis with tenecteplase in late-window posterior-circulation stroke patients, noting that thrombectomy’s “dominant” treatment effect seemingly “leaves little room” for the drug to further ameliorate functional outcomes. This notion is reinforced by the fact that, despite successful pre-thrombectomy reperfusion on imaging occurring more frequently in the treatment arm versus the control arm (5.4% vs 1.2%, respectively), successful reperfusion was achieved at a similar rate across the two groups following completion of the procedure. The presenter also stated that the “selective use” of tenecteplase in late-window bridging IVT may yet warrant further study.
A key point of difference between ATTENTION LATE and TNK-PLUS was their enrolment criteria, with the latter choosing to include patients who had anterior-circulation MCA occlusions in their M1 or proximal M2 segments rather than posterior-circulation occlusions involving the basilar artery. Yunyun Xiong (Capital Medical University, Beijing, China), who presented late-breaking data from TNK-PLUS at ISC, noted that tenecteplase has already demonstrated clinical benefits versus standard medical care in late-window LVO patients within the TRACE III RCT, while the BRIDGE-TNK trial also saw tenecteplase-based bridging therapy result in improved rates of functional independence versus direct thrombectomy inside 4.5 hours.
TNK-PLUS attempted to establish the superiority of tenecteplase plus thrombectomy over thrombectomy alone via a prospective RCT conducted across 40 sites in China. It enrolled 391 proximal MCA occlusion stroke patients with salvageable brain tissue presenting 4.5–24 hours from symptom onset, randomising these patients to undergo a thrombectomy procedure either with or without being administered 0.25mg/kg of tenecteplase beforehand.
The trial’s primary endpoint of 90-day mRS 0–2 was achieved in 44.2% of patients in the tenecteplase arm versus 43.2% in the direct-thrombectomy arm, representing a statistically insignificant difference between the two groups (effect size, 1.01). A range of secondary endpoints in TNK-PLUS, including mRS 0–1 at 90 days, major neurological improvement at 72 hours, change in NIHSS score at seven days, and reperfusion at 24 hours, were also comparable between bridging IVT and direct thrombectomy. Furthermore, the rate of sICH within 36 hours was found to be higher with (5.1%) versus without (2.6%) tenecteplase—although this did not lead to any between-group differences in mortality at 90 days. Xiong also noted that subgroup analyses revealed similar findings on all of these outcome measures.
“Considering TIMELESS was neutral, and we studied the most promising subgroup from TIMELESS, bridging therapy with tenecteplase is not recommended in this population,” the presenter concluded, before also averring that the role for tenecteplase in LVO stroke patients who need to be transferred to undergo a mechanical thrombectomy is an area requiring further research.
“We must underline the fact that these trials [ATTENTION LATE and TNK-PLUS] were done in comprehensive stroke centres, which means they included patients who had reached a thrombectomy-capable hospital and were already enroute to the procedure when given tenecteplase,” Menon explained. “That means the drug has a very short dwell time—in TNK-PLUS, for example, it was less than 30 minutes.
“So, these trials show conclusively that giving tenecteplase when thrombectomy is available—and available very soon—does not benefit patients. However, that’s not to say that thrombolysis cannot help when you have a longer dwell time, if patients are transferred or thrombectomy is delayed, and previous results from the TRACE III trial also suggest that tenecteplase can benefit late-window patients with LVOs who are not candidates for thrombectomy.”
