Relationship Between the eTICI Score Before Randomization and 90-Day Outcome: A Post Hoc Analysis of ANGEL-TNK Trial

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.