I'd have to argue it's not incomplete reperfusion at all. My theory would be the neuronal cascade of death is occurring. How the hell are you DIRECTLY measuring incomplete reperfusion? I bet you're thinking that if reperfusion is complete neuronal death would stop. Wrong!
IA Thrombolysis Post-Stroke Thrombectomy: More Uncertainty
The strategy of administering intra-arterial (IA) thrombolysis immediately after thrombectomy in patients with acute ischemic stroke has come under renewed scrutiny after results from the TECNO trial showed no clear improvement in reperfusion rates with this approach.
The idea of giving a dose of IA thrombolysis immediately after thrombectomy in patients with acute ischemic stroke has become more uncertain, with the results of a new trial showing no clear benefit on reperfusion rates using this approach.
These results are in contrast to the previous CHOICE-2 trial, first presented earlier this year at the International Stroke Conference, and now published in JAMA. CHOICE-2 showed positive results in terms of good functional outcomes with an IA thrombolysis strategy, although this was dampened by an increased mortality rate.
The TECNO trial showed that IA tenecteplase did not significantly improve early or late reperfusion rates in stroke patients with incomplete reperfusion following mechanical thrombectomy.
“While IA tenecteplase was found to be safe regarding intracranial bleeding, the results highlight the need for further refinement of patient selection and treatment protocols in this setting,” TECNO investigator, Johannes Kaesmacher, MD, University Hospital Bern in Bern, Switzerland, concluded.
The study was presented on May 6 at the European Stroke Organization Conference (ESOC) 2026.
Targeting Residual Clot after Thrombectomy
Kaesmacher explained that incomplete reperfusion remains a common and clinically important challenge following mechanical thrombectomy. Direct IA administration of thrombolysis offers the advantage of targeted drug delivery to the residual clot.
The TECNO trial, conducted at 20 high-volume stroke centres in Europe, randomly assigned 156 patients with incomplete reperfusion (TICI 2b and 2c) after mechanical thrombectomy to a 3-mg dose of IA tenecteplase or control.
The primary efficacy outcomes are early and late reperfusion, as defined by reperfusion improvement on angiography images 25 minutes after randomisation, or complete reperfusion at 24 hours on MR/CT perfusion imaging.
In the primary analysis, improved early reperfusion was observed in 39% of patients randomized to tenecteplase compared with 36% in the control group, corresponding to an adjusted risk difference of 3.4% (95% CI, -15% to 21.7%), which was not statistically significant.
Late reperfusion at 24 hours was observed in 51% vs 40% of patients (adjusted risk difference, 15.4%; 95% CI, -3.3% to 32.9%) and was also nonsignificant.
From a safety perspective, symptomatic intracranial hemorrhage occurred in 5.2% of patients in the tenecteplase group compared with 8.6% in the control group, confirming an acceptable safety profile with respect to intracranial bleeding.
At 90 days, functional independence (modified Rankin Scale [mRS], 0-2) was achieved by 27% of patients in the tenecteplase group compared with 38% in the control group (adjusted common odds ratio, 0.60; 95% CI, 0.34-1.06).
Concerning Safety Signals
The investigators emphasized that the trial was designed and powered to evaluate reperfusion as its primary endpoint and that definitive conclusions regarding clinical outcomes should not be drawn from these data alone.
“Taken alone, these findings do not support the routine administration of intra-arterial tenecteplase as a pharmacological adjunct in cases of incomplete reperfusion,” the researchers noted.
The TECNO results conflict with the previous CHOICE-2 trial. It was conducted at 14 stroke centers in Spain, 440 patients with acute ischemic stroke due to large vessel occlusion treated with thrombectomy within 24 hours and achieving good reperfusion were randomly assigned to IA alteplase (0.225 mg/kg; maximum dose of 20 mg/kg) infused over 15 minutes or control.
The primary outcome was an excellent functional outcome at 90 days, defined as a mRS score of 0 or 1. This was achieved by 57.5% of patients in the alteplase group vs 42.5% of patients in the control arm, giving an adjusted risk difference of 15.0% (95% CI, 5.7%-24.3%; P = .002).
However, there were some concerning safety signals including an increase in 90-day mortality in the alteplase group (12.1%) vs 6.4% in the thrombectomy-alone group.
In an editorial accompanying the publication of CHOICE-2, Urs Fischer, MD, Johannes Kaesmacher, MD, both from University Hospital Bern, and Adrien ter Schiphorst, MD, of Montpellier University Hospital, Montpellier, France, noted that the higher mortality observed in the alteplase group was driven by a striking excess of early deaths during the first week (10 patients vs 2 patients).
However, this imbalance was not readily explained by an increase in symptomatic intracranial hemorrhage, which remained rare and did not differ significantly between the groups.
“A critical question remains regarding whether the benefit concentrated at the most favorable end of the disability spectrum truly offsets a near doubling in mortality,” they wrote.
With respect to the mechanism underlying the clinical effect, the editorialists note that the imaging findings did not demonstrate reduced infarct expansion. However, perfusion imaging suggested a substantially lower rate of residual microvascular hypoperfusion in the alteplase group.
They conclude that the CHOICE-2 findings reinforce the idea that achieving tissue-level reperfusion after thrombectomy remains an important therapeutic goal and support continued investigation of adjunctive pharmacologic therapies, even after technically successful recanalization.
At the same time, they caution that the results are not yet sufficient to change clinical practice and emphasize that further studies are needed to determine which patients are most likely to benefit, which imaging profiles are most appropriate, and what safety tradeoffs may be involved.
More Data Needed
In a discussion at the ESOC meeting, Kaesmacher suggested that the dose of tenecteplase used may be one point to consider regarding the neutral results of the TECNO trial, pointing out that previous trials have used higher equivalent doses of thrombolysis.
He also noted that the tenecteplase was administered very quickly in the TECNO trial (over 1 minute).
“So maybe we need a little bit more or longer duration of the injection,” he said.
In addition, previous trials include more patients with good reperfusion rates, whereas the TECNO trial enrolled more patients with partial reperfusion rates.
“We have to dig more into the data. We need to find out how the whole concept of intra-arterial thrombolysis is working — it is actually reaching the proximal end — before planning another trial,” he concluded.
Commenting on the use of IA thrombolysis after thrombectomy, Peter Kelly, MD, of University College Dublin in Dublin, Ireland, described the strategy as “very promising,” while noting that many questions remain unanswered.
These include the need for further analyses of recanalization levels and lesion volume, as well as a better understanding of the optimal timing of imaging assessments.
“It will also be interesting to see whether intra-arterial thrombolysis is targeting the microcirculation or whether it is the no reflow phenomenon, which is maybe more of a macrovascular issue,” he said.
Kelly added that several trials of this approach have now been conducted, and more information may come from meta-analyses of all the available data.
The TECNO trial was supported by the Insel Gruppe AG and University Hospital Bern. The CHOICE-2 study was supported by the Instituto de Salud Carlos III and by the European Union Next Generation EU/Mecanismo Para la Recuperación y la Resiliencia/Plan de Recuperación, Transformación y Resiliencia. The investigators reported having no relevant disclosures.
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