Abstract 92: Tenecteplase Treatment And Thrombus Characteristics Associated With Early Reperfusion - An EXTEND-IA TNK Trials Analysis

Abstract

Background: Intracranial occlusion site, contrast permeability, and clot burden are thrombus characteristics that influence alteplase-associated reperfusion. In this study, we assessed the reperfusion efficacy of tenecteplase and alteplase in subgroups based on these characteristics in a pooled analysis of the EXTEND-IA TNK trials. Methods: Patients with large vessel occlusion (LVO) were randomized to treatment with tenecteplase (0.25mg/kg or 0.4mg/kg) or alteplase (0.9mg/kg) prior to thrombectomy. The primary outcome, early reperfusion, was defined as the absence of retrievable thrombus or >50% reperfusion on initial angiographic assessment. We compared the treatment effect of tenecteplase versus alteplase overall, and in subgroups based on intracranial occlusion site, the presence of contrast permeability (measured via residual flow grades), and clot burden (measured via clot burden scores), whilst adjusting for relevant covariates using mixed effects logistic regression models. Results: Among the 465 patients in the primary analysis, early reperfusion occurred in 18% (84/465). Tenecteplase was associated with a higher odds of early reperfusion (tenecteplase: 75/369 [20%] vs. alteplase: 9/96 [9%], aOR: 2.18 [95%CI: 1.03-4.63]). The difference between thrombolytics was most notable in distal M1 or M2 occlusions (tenecteplase: 53/176 [30%] vs. alteplase: 4/42 [10%], aOR: 3.73 [95%CI: 1.25-11.11]), thrombi with contrast permeability (tenecteplase: 38/160 [24%] vs. alteplase: 5/48 [10%], aOR: 2.83 [95%CI: 1.00-8.05]), and in low clot burden occlusions (tenecteplase: 66/261 [25%] vs. alteplase: 5/67 [7%], aOR: 3.93 [95%CI: 1.50-10.33]). Both thrombolytics had limited early reperfusion efficacy in proximal occlusions (ICA: tenecteplase 1/73 [1%] vs. alteplase 1/19 [5%]) and in high clot burden occlusions (tenecteplase: 9/108 [8%] vs. alteplase: 4/29 [14%], aOR: 0.58 [95%CI: 0.16-2.06]). Conclusions: Tenecteplase demonstrates superior early reperfusion versus alteplase in distal LVO, in contrast-permeable thrombi, and in lesions with low clot burden. Reperfusion efficacy remains limited in ICA occlusions and lesions with high clot burden. Further improvements in intravenous thrombolytics are required.