Department of Neurology, Royal Melbourne Hospital, University of Melbourne, Parkville, Australia (V.Y., L.C., P.G., J.B., N.Y., B.Y., G.S., M.W.P., G.A.D., S.M.D., B.C.V.C.).
Department of Medicine, Austin Health, Heidelberg, Australia (J.B., V.T.).
Stroke. 2023 Mar;54(3):706-714. doi: 10.1161/STROKEAHA.122.041061. Epub 2023 Feb 2.
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).
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.
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]; =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]; =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]; =0.16).
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.
颅内闭塞部位、对比通透性和血栓负荷是影响阿替普酶相关再灌注的血栓特征。在这项 EXTEND-IA TNK 试验（Tenecteplase 与阿替普酶在血管内治疗缺血性卒中前）的汇总分析中，我们根据这些特征，在亚组中评估了替奈普酶和阿替普酶的再灌注效果。
在澳大利亚和新西兰的医院（2015-2019 年），将大血管闭塞的患者随机分配接受替奈普酶（0.25 或 0.4 mg/kg）或阿替普酶治疗后进行血栓切除术。主要结局为早期再灌注，定义为无可回收血栓或首过血管造影显示＞50%再灌注。我们比较了替奈普酶与阿替普酶的总体效果，以及基于计算机断层血管造影术测量的以下特征的亚组效果：颅内闭塞部位、对比通透性（通过残留血流分级测量）和血栓负荷（通过血栓负荷评分测量）。我们使用混合效应逻辑回归模型对协变量进行了调整。
与阿替普酶相比，替奈普酶早期再灌注的几率更高（75/369 [20%] 与阿替普酶：9/96 [9%]，调整后的优势比[aOR]，2.18 [95%CI，1.03-4.63]）。在低血栓负荷病变中，替奈普酶与阿替普酶的差异显著（替奈普酶：66/261 [25%] 与阿替普酶：5/67 [7%]，aOR，3.93 [95%CI，1.50-10.33]），而在高血栓负荷病变中，替奈普酶与阿替普酶的差异不显著（替奈普酶：9/108 [8%] 与阿替普酶：4/29 [14%]，aOR，0.58 [95%CI，0.16-2.06]；=0.01）。我们没有观察到对比通透性与替奈普酶治疗效果之间的关联（存在通透性：aOR，2.83 [95%CI，1.00-8.05] 与不存在通透性：aOR，1.98 [95%CI，0.65-6.03]；=0.62）。替奈普酶在远端 M1 或 M2 闭塞中效果更好（53/176 [30%] 与阿替普酶：4/42 [10%]，aOR，3.73 [95%CI，1.25-11.11]），但阿替普酶在颈内动脉闭塞中疗效有限（替奈普酶 1/73 [1%] 与阿替普酶 1/19 [5%]，aOR，0.22 [95%CI，0.01-3.83]；=0.16）。
与阿替普酶相比，替奈普酶在低血栓负荷病变中表现出更好的早期再灌注效果。在颈内动脉闭塞和高血栓负荷病变中，再灌注效果仍然有限。需要进一步创新溶栓治疗。
