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

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 trial (Tenecteplase Versus Alteplase Before Endovascular Therapy for Ischemic Stroke). Methods: Patients with large vessel occlusion were randomized to treatment with tenecteplase (0.25 or 0.4 mg/kg) or alteplase before thrombectomy in hospitals across Australia and New Zealand (2015–2019). The primary outcome, early reperfusion, was defined as the absence of retrievable thrombus or >50% reperfusion on first-pass angiogram. We compared the effect of tenecteplase versus alteplase overall, and in subgroups, based on the following measured with computed tomography angiography: intracranial occlusion site, contrast permeability (measured via residual flow grades), and clot burden (measured via clot burden scores). We adjusted for covariates using mixed effects logistic regression models. Results: Tenecteplase was associated with higher odds of early reperfusion (75/369 20% versus alteplase: 9/96 9%, adjusted odds ratio aOR, 2.18 95% CI, 1.03–4.63). The difference between thrombolytics was notable in occlusions with low clot burden (tenecteplase: 66/261 25% versus alteplase: 5/67 7%, aOR, 3.93 95% CI, 1.50–10.33) when compared to high clot burden lesions (tenecteplase: 9/108 8% versus alteplase: 4/29 14%, aOR, 0.58 95% CI, 0.16–2.06; P interaction =0.01). We did not observe an association between contrast permeability and tenecteplase treatment effect (permeability present: aOR, 2.83 95% CI, 1.00–8.05 versus absent: aOR, 1.98 95% CI, 0.65–6.03; P interaction =0.62). Tenecteplase treatment effect was superior with distal M1 or M2 occlusions (53/176 30% versus alteplase: 4/42 10%, aOR, 3.73 95% CI, 1.25–11.11), but both thrombolytics had limited efficacy with internal carotid artery occlusions (tenecteplase 1/73 1% versus alteplase 1/19 5%, aOR, 0.22 95% CI, 0.01–3.83; P interaction =0.16). Conclusions: Tenecteplase demonstrates superior early reperfusion versus alteplase in lesions with low clot burden. Reperfusion efficacy remains limited in internal carotid artery occlusions and lesions with high clot burden. Further innovation in thrombolytic therapies are required.