Kim Jong S, Kim Yeon-Jung, Lee Kyung Bok, Cha Jae Kwan, Park Jong-Moo, Hwang Yangha, Kim Eung-Gyu, Rha Joung-Ho, Koo Jaseong, Kim Jei, Kim Yong-Jae, Seo Woo-Keun, Kim Dong-Eog, Robinson Thompson G, Lindley Richard I, Wang Xia, Chalmers John, Anderson Craig S
Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Department of Neurology, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Korea.
J Stroke. 2018 Jan;20(1):131-139. doi: 10.5853/jos.2017.01578. Epub 2018 Jan 31.
Following the positive results from recent trials on endovascular therapy (EVT), bridging therapy (intravenous alteplase plus EVT) is increasingly being used for the treatment of acute ischemic stroke. However, the optimal dose of intravenous alteplase remains unknown in centers where bridging therapy is actively performed. The optimal dose for eventual recanalization and positive clinical outcomes in patients receiving bridging therapy also remains unknown.
In this prospective Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) sub-study, we explored the outcomes following treatment with two different doses (low- [0.6 mg/kg] or standard-dose [0.9 mg/kg]) of intravenous alteplase across 12 Korean centers where EVT is actively performed. The primary endpoint was a favorable outcome at 90 days (modified Rankin Scale scores 0 to 1). Secondary endpoints included symptomatic intracerebral hemorrhage (ICH) in all patients, and the recanalization rate and favorable outcome in patients who underwent cerebral angiography for EVT (ClinicalTrials.gov, number NCT01422616).
Of 351 patients, the primary outcome occurred in 46% of patients in both the standard-(80/173) and low-dose (81/178) groups (odds ratio [OR], 1.14; 95% confidence interval [CI], 0.72 to 1.81; =0.582), although ICHs tended to occur more frequently in the standard-dose group (8% vs. 3%, =0.056). Of the 67 patients who underwent cerebral angiography, there was no significant difference in favorable functional outcome between the standard- and low-dose groups (39% vs. 21%; OR, 2.39; 95% CI, 0.73 to 7.78; =0.149).
There was no difference in functional outcome between the patients receiving different doses of alteplase in centers actively performing bridging therapy.
鉴于近期血管内治疗（EVT）试验取得了阳性结果，桥接治疗（静脉注射阿替普酶联合EVT）越来越多地用于急性缺血性卒中的治疗。然而，在积极开展桥接治疗的中心，静脉注射阿替普酶的最佳剂量仍不明确。接受桥接治疗的患者实现最终再通及获得良好临床结局的最佳剂量也尚不明确。
在这项前瞻性高血压强化控制与溶栓治疗卒中研究（ENCHANTED）的子研究中，我们在12个积极开展EVT的韩国中心，探讨了两种不同剂量（低剂量[0.6mg/kg]或标准剂量[0.9mg/kg]）静脉注射阿替普酶治疗后的结局。主要终点为90天时的良好结局（改良Rankin量表评分0至1分）。次要终点包括所有患者的症状性颅内出血（ICH），以及接受EVT脑血管造影患者的再通率和良好结局（ClinicalTrials.gov，编号NCT01422616）。
在351例患者中，标准剂量组（80/173）和低剂量组（81/178）的主要结局发生率均为46%（优势比[OR]，1.14；95%置信区间[CI]，0.72至1.81；P=0.582），尽管标准剂量组ICH的发生频率往往更高（8%对3%，P=0.056）。在67例接受脑血管造影的患者中，标准剂量组和低剂量组的良好功能结局无显著差异（39%对21%；OR，2.39；95%CI，0.73至7.78；P=0.149）。
在积极开展桥接治疗的中心，接受不同剂量阿替普酶治疗的患者在功能结局方面无差异。
