Department of Neurology, Fort-de-France University Hospital, Fort-de-France, Martinique, French West Indies.
CNS Drugs. 2012 Apr 1;26(4):309-18. doi: 10.2165/11631500-000000000-00000.
The only currently approved treatment for acute ischaemic stroke (AIS) is alteplase, a thrombolytic agent given intravenously (IV) within 4.5 hours of symptom onset, in an attempt to reopen occluded intracerebral arteries. However, no more than 5% of all AIS patients receive IV alteplase, mainly because of too long symptom-onset-to-hospital intervals. Moreover, this strategy is effective for less than half of the patients treated within the therapeutic window. Early recanalization is the most powerful prognostic factor, and novel drugs or therapeutic strategies are primarily aimed at improving alteplase efficacy to rapidly and safely reopen the occluded arteries. Because IV alteplase-resistant thrombi are those with the largest clot burden, responsible for the most devastating brain-tissue infarctions, development of novel approved AIS therapies is an urgent priority. At present, in the absence of controlled trials, no valid recommendations can be made. However, the most promising emerging strategy is a combination of standard or low-dose IV alteplase with an intra-arterial (IA) procedure, including additional endovascular thrombolytic and/or mechanical clot retrieval. Notably, results of open trials using the IA route had relatively disappointing clinical outcomes, despite remarkable arterial recanalization rates. Controlled trials are urgently needed to evaluate strategies including an IA route. In addition, logistic and cost constraints will likely limit their routine use, even in industrialized countries. Combining of another IV drug and IV alteplase is a far less studied option, although much easier to implement. Add-on IV drugs could be an antiplatelet glycoprotein (GP) IIb/IIIa receptor antagonist, a direct thrombin inhibitor or a second thrombolytic agent, e.g. tenecteplase. However, neuroimaging to measure the clot burden and infarction size will probably be necessary to predict IV alteplase failure and the subsequent use of these eventual additional therapies.
目前，急性缺血性脑卒中（AIS）唯一被批准的治疗方法是阿替普酶，这是一种溶栓剂，在症状发作后 4.5 小时内通过静脉内（IV）给药，试图重新开放闭塞的颅内动脉。然而，只有不到 5%的 AIS 患者接受 IV 阿替普酶治疗，主要是因为症状发作到医院的时间间隔太长。此外，该策略对治疗窗内接受治疗的患者只有不到一半有效。早期再通是最强的预后因素，新型药物或治疗策略主要旨在提高阿替普酶的疗效，以快速、安全地重新开放闭塞的动脉。因为 IV 阿替普酶抵抗的血栓是那些具有最大血栓负荷的血栓，负责最具破坏性的脑组织梗死，因此开发新型批准的 AIS 治疗方法是当务之急。目前，由于缺乏对照试验，因此无法提出有效的建议。然而，最有前途的新兴策略是将标准或低剂量 IV 阿替普酶与动脉内（IA）治疗相结合，包括额外的血管内溶栓和/或机械血栓切除术。值得注意的是，尽管动脉再通率显著，但使用 IA 途径的开放性试验结果临床结局相对令人失望。迫切需要进行对照试验来评估包括 IA 途径在内的治疗策略。此外，物流和成本限制可能会限制它们的常规使用，即使在工业化国家也是如此。另一种 IV 药物与 IV 阿替普酶联合使用是一种研究得较少的选择，尽管实施起来要容易得多。附加的 IV 药物可以是抗血小板糖蛋白（GP）IIb/IIIa 受体拮抗剂、直接凝血酶抑制剂或第二种溶栓剂，例如替奈普酶。然而，神经影像学测量血栓负荷和梗死面积可能是预测 IV 阿替普酶失败和随后使用这些最终附加治疗的必要手段。
