Sablot D, Leibinger F, Dutray A, Van Damme L, Nguyen Them L, Farouil G, Jebali C, Arquizan C, Ibanez-Julia M-J, Laverdure A, Allou T, Chaabane W, Fadat B, Olivier N, Smadja P, Tardieu M, Lachcar M, Mas J, Ousji A, Jurici S, Mourand I, Ferraro A, Dumitrana A, Bensalah Z M, Damon F, Tincau O-A, Valverde D, Mekue-Fotso V, Bonafe A, Ortega L, Gaillard N
Neurology Department, Perpignan, France; Regional Health agency of Occitanie, Montpellier, France.
Intensive Care Unit, Perpignan, France.
Rev Neurol (Paris). 2022 Dec;178(10):1079-1089. doi: 10.1016/j.neurol.2022.08.003. Epub 2022 Nov 3.
Intravenous thrombolysis (IVT) use for acute ischemic stroke (AIS) varies among countries, partly due to guidelines and product labeling changes. The study aim was to identify the characteristics of patients with AIS treated with off-label IVT and to determine its safety when performed in a primary stroke center (PSC).
This observational, single-center study included all consecutive patients admitted to Perpignan PSC for AIS and treated with IVT and patients transferred for EVT, between January 1, 2015 and December 31, 2019. Data of patients treated with IVT according to ("in-label group") or outside ("off-label") the initial guidelines and manufacturer's product specification were compared. Safety was assessed using symptomatic intracerebral hemorrhage (SIH) as the main adverse event.
Among the 892 patients in the database (834 screened by MRI, 93.5%), 746 were treated by IVT: 185 (24.8%) "in-label" and 561 (75.2%) "off-label". In the "off-label" group, 316 (42.4% of the cohort) had a single criterion for "off-label" use, 197 (26.4%) had two, and 48 (6.4%) had three or more criteria, without any difference in IVT safety pattern among them. SIH rates were comparable between the "off-label" and "in-label" groups (2.7% vs. 1.1%, P=0.21); early neurological deterioration and systematic adverse event due to IVT treatment were similar in the 2 groups. "Off-label" patients had higher in-hospital (8.7% vs. 3.8%, P=0.05) and 3-month mortality rates (12.1% vs 5.4%, P<0.01), but this is explained by confounding factors as they were older (76 vs 67 years, P<0.0001) and more dependent (median modified Rankin scale score 0.4 vs 0.1, P<0.0001) at admission.
"Off-label" thrombolysis for AIS seems to be safe and effective in the routine setting of a primary stroke center.
各国急性缺血性卒中（AIS）静脉溶栓（IVT）的使用情况存在差异，部分原因是指南和产品标签的变化。本研究旨在确定接受超说明书IVT治疗的AIS患者的特征，并确定在初级卒中中心（PSC）进行IVT时的安全性。
这项观察性单中心研究纳入了2015年1月1日至2019年12月31日期间因AIS入住佩皮尼昂PSC并接受IVT治疗的所有连续患者，以及转来接受血管内治疗（EVT）的患者。比较了根据初始指南和制造商产品说明书接受IVT治疗的患者（“标签内组”）和超出此范围（“超说明书”）治疗的患者的数据。以症状性脑出血（SIH）作为主要不良事件评估安全性。
数据库中的892例患者中（834例接受了MRI筛查，占93.5%），746例接受了IVT治疗：185例（24.8%）为“标签内”治疗，561例（75.2%）为“超说明书”治疗。在“超说明书”组中，316例（占队列的42.4%）有一项“超说明书”使用标准，197例（26.4%）有两项，48例（6.4%）有三项或更多标准，它们之间的IVT安全模式无差异。“超说明书”组和“标签内”组的SIH发生率相当（2.7%对1.1%，P=0.21）；两组IVT治疗导致的早期神经功能恶化和系统性不良事件相似。“超说明书”治疗的患者住院死亡率较高（8.7%对3.8%，P=0.05），3个月死亡率也较高（12.1%对5.4%，P<0.01），但这可以用混杂因素来解释，因为他们入院时年龄较大（76岁对67岁，P<0.0001）且依赖性更强（改良Rankin量表中位评分0.4对0.1，P<0.0001）。
在初级卒中中心的常规环境中，AIS的“超说明书”溶栓似乎是安全有效的。
