Key result
Intraarterial tenecteplase after EVT yields ~2.1-fold higher excellent recovery in eTICI 2b50-67 patients.
Why the study?
Recent trials of intraarterial thrombolysis after successful thrombectomy recanalization showed inconsistent results, leaving its efficacy and safety across post-thrombectomy eTICI score strata unclear.
Does intraarterial tenecteplase improve 90-day functional outcomes (mRS 0-1) compared to standard medical management in patients with anterior circulation large artery occlusion stratified by eTICI score after mechanical thrombectomy?
RCT (n=253)
Open-label, blinded end point
1:1
Yes
Does intraarterial tenecteplase improve 90-day functional outcomes (mRS 0-1) compared to standard medical management in patients with anterior circulation large artery occlusion stratified by eTICI score after mechanical thrombectomy?
Adjunctive intraarterial tenecteplase after thrombectomy improves 90-day excellent functional outcomes exclusively in patients with incomplete (eTICI 2b50-67) rather than near-complete/complete (eTICI 2c-3) reperfusion, where it instead increases intracranial hemorrhage risk.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“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.”
“We still need to conduct a direct analysis of individual participant data from this and other trials — an individual patient-level meta-analysis — to establish a robust, evidence-based recommendation.”
“Endovascular treatment can help restore blood flow in a blocked large blood vessel. However, it might not improve blood flow in the smaller vessels and microcirculation in the area. This clinical trial tests whether delivering tenecteplase directly into the affected artery after endovascular treatment can break up blood clots in the small vessels and improve blood flow, reducing the amount of brain tissue that lacks blood supply.”
Stratified eTICI analysis may inform IA thrombolysis decisions post-thrombectomy; leaves open optimal selection pending dedicated trials.
BACKGROUND: Successful thrombectomy recanalization combined with intraarterial thrombolysis showed potential benefits in achieving excellent outcomes in recent trials, but the results were inconsistent. We performed this study to investigate the efficacy and safety of interarterial thrombolysis in patients stratified by expanded Thrombolysis in Cerebral Infarction (eTICI) score after thrombectomy. METHODS: This is a prespecified secondary analysis of the ANGEL-TNK trial (Intraarterial Recombinant Human TNK-tPA Thrombolysis for Acute LVO After Successful Mechanical Thrombectomy Recanalization; multicenter, randomized, open-label, blinded end point). Participants who had anterior circulation large artery occlusion were enrolled and randomized (1:1) to interarterial tenecteplase (TNK; 0.125 mg/kg) or standard medical management after eTICI 2b50 to 3 reperfusion. The primary outcome was the rate of 90-day modified Rankin Scale score 0 to 1. Safety outcomes included symptomatic intracranial hemorrhage and any intracranial hemorrhage within 48 hours, and death within 90 days. RESULTS: Of the 253 patients enrolled, 164 were in the eTICI 2b50 to 67 group, and 89 were in the eTICI 2c to 3 group. Interarterial TNK after EVT was associated with a higher rate of modified Rankin Scale score 0 to 1 at 90 days in patients with an eTICI score of 2b50 to 67 (39 [44.8%] versus 15 [19.5%]; relative risk, 2.08 [95% CI, 1.35–3.21]; P =0.001), but not in those with eTICI 2c to 3 (12 [30.8%] versus 19 [38.0%]; relative risk, 0.84 [95% CI, 0.29–2.44]; P =0.749). In the eTICI 2c to 3 group, interarterial TNK resulted in more cases of any intracranial hemorrhage within 48 hours (13 [33.3%] versus 10 [20.0%]; relative risk, 1.70 [95% CI, 1.05–2.77]; P =0.032), but not in the eTICI 2b50 to 67 group (18 [20.7%] versus 25 [32.5%]; relative risk, 0.65 [95% CI, 0.34–1.22]; P =0.176). The difference was not observed in symptomatic intracranial hemorrhage within 48 hours or death within 90 days in either group. CONCLUSIONS: Interarterial TNK after EVT provides additional benefits for excellent outcomes, defined as a modified Rankin Scale score of 0 to 1 at 90 days, in patients with an eTICI score of 2b50 to 67, but not in those with eTICI 2c to 3. It increases the risk of any intracranial hemorrhage in patients with an eTICI score of 2c to 3, without elevating the risk of symptomatic intracranial hemorrhage or death. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05624190.
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Zhang et al. (2026) conducted an RCT in Acute anterior circulation large artery occlusion with successful mechanical thrombectomy recanalization (eTICI 2b50 to 3) (n=253). Intraarterial tenecteplase vs. Standard medical management was evaluated on 90-day modified Rankin Scale score 0 to 1 (in eTICI 2b50 to 67 subgroup) (RR 2.08, 95% CI 1.35-3.21, p=0.001). Intraarterial tenecteplase after EVT increased 90-day mRS 0-1 in eTICI 2b50-67 patients (44.8% vs 19.5%; RR 2.08; 95% CI 1.35-3.21; P=0.001), but not in eTICI 2c-3.
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