Outcomes of Intra‐Arterial Tenecteplase after Endovascular Reperfusion for Acute Ischemic Stroke Due to Cardioembolism and Non‐Cardioembolism: A Secondary Analysis of the POST ‐ TNK Trial

OBJECTIVE: This study aimed to evaluate the safety and effectiveness of adjunctive intra-arterial tenecteplase (TNK) in patients with acute ischemic stroke (AIS) due to cardioembolism (CE) and non-CE who achieved near-complete to complete reperfusion (defined as an expanded thrombolysis in cerebral infarction score of 2c-3) following endovascular treatment (EVT). METHODS: This prespecified secondary analysis of the POST-TNK randomized, open-label, blinded outcome assessment trial categorized 540 patients by stroke etiology into CE (n = 272) and non-CE (n = 268) subgroups. The primary outcome was freedom from disability at 90 days, defined as a modified Rankin Scale score of 0 to 1. Safety outcomes included 90-day mortality, symptomatic intracranial hemorrhage (sICH) within 48 hours, and any intracranial hemorrhage (ICH) within 48 hours. RESULTS: Among 272 patients with CE (median age, 73 years [interquartile range, 66-78]; 47.1% male), 137 were assigned to the control group and 135 to the intra-arterial TNK group. Compared with the control group, intra-arterial TNK was associated with significantly higher odds of freedom from disability at 90 days (adjusted odds ratio, 1.80; 95% confidence interval [CI], 1.02-3.16; p = 0.04; inverse probability of treatment weighting adjusted odds ratio, 1.58; 95% CI, 1.12-2.22; p = 0.01). No significant differences were observed in 90-day mortality, sICH, or any ICH within 48 hours between groups. Conversely, intra-arterial TNK was not associated with improved functional outcomes in patients with AIS due to non-CE. INTERPRETATION: In patients with AIS due to CE who achieved near-complete to complete reperfusion after EVT, adjunctive intra-arterial TNK was associated with a higher likelihood of freedom from disability at 90 days, without increasing the risk of mortality or ICH. However, this benefit was not observed in AIS patients due to non-CE. ANN NEUROL 2026.