Tsivgoulis Georgios, Kargiotis Odysseas, De Marchis Gianmarco, Kohrmann Martin, Sandset Else Charlotte, Karapanayiotides Theodore, de Sousa Diana Aguiar, Sarraj Amrou, Safouris Apostolos, Psychogios Klearchos, Vadikolias Konstantinos, Leys Didier, Schellinger Peter D, Alexandrov Andrei V
Second Department of Neurology, National & Kapodistrian University of Athens, School of Medicine, Iras 39, Gerakas Attikis, Athens 15344, Greece.
Stroke Unit, Metropolitan Hospital, Piraeus, Greece.
Ther Adv Neurol Disord. 2021 Feb 26;14:1756286421997368. doi: 10.1177/1756286421997368. eCollection 2021.
Intravenous thrombolysis (IVT) represents the only systemic reperfusion therapy able to reverse neurological deficit in patients with acute ischemic stroke (AIS). Despite its effectiveness in patients with or without large vessel occlusion, it can be offered only to a minority of them, because of the short therapeutic window and additional contraindications derived from stringent but arbitrary inclusion and exclusion criteria used in landmark randomized controlled clinical trials. Many absolute or relative contraindications lead to disparities between the official drug label and guidelines or expert recommendations. Based on recent advances in neuroimaging and evidence from cohort studies, off-label use of IVT is increasingly incorporated into the daily practice of many stroke centers. They relate to extension of therapeutic time windows, and expansion of indications in co-existing conditions originally listed in exclusion criteria, such as use of alternative thrombolytic agents, pre-treatment with antiplatelets, anticoagulants or low molecular weight heparins. In this narrative review, we summarize recent randomized and real-world data on the safety and efficacy of off-label use of IVT for AIS. We also make some practical recommendations to stroke physicians regarding the off-label use of thrombolytic agents in complex and uncommon presentations of AIS or other conditions mimicking acute cerebral ischemia. Finally, we provide guidance on the risks and benefits of IVT in numerous AIS subgroups, where equipoise exists and guidelines and treatment practices vary.
静脉溶栓（IVT）是唯一能够逆转急性缺血性卒中（AIS）患者神经功能缺损的全身再灌注治疗方法。尽管其对有或无大血管闭塞的患者均有效，但由于治疗窗短以及标志性随机对照临床试验中使用的严格但随意的纳入和排除标准导致的其他禁忌证，只有少数患者能够接受该治疗。许多绝对或相对禁忌证导致官方药品标签与指南或专家建议之间存在差异。基于神经影像学的最新进展和队列研究的证据，IVT的超说明书使用越来越多地被纳入许多卒中中心的日常实践中。这些实践涉及治疗时间窗的延长以及最初列入排除标准的并存疾病的适应证扩展，如使用替代溶栓药物、抗血小板药物、抗凝剂或低分子肝素进行预处理。在本叙述性综述中，我们总结了近期关于IVT超说明书用于AIS的安全性和有效性的随机和真实世界数据。我们还就AIS复杂和罕见表现或其他模拟急性脑缺血情况中超说明书使用溶栓药物向卒中医生提出了一些实用建议。最后，我们为存在 equipoise 且指南和治疗实践各异的众多AIS亚组中IVT的风险和益处提供指导。
