Meretoja Atte, Tatlisumak Turgut
Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland.
CNS Drugs. 2008;22(8):619-29. doi: 10.2165/00023210-200822080-00001.
Treatment of acute ischaemic stroke aims to recanalize the occluded artery, salvage the at-risk brain tissue and thus minimize neurological sequelae. Efforts a decade ago have led to the only currently approved medical treatment for acute ischaemic stroke, i.e. intravenous alteplase given within 3 hours of stroke onset. Recanalization occurs in only one-half of the patients receiving alteplase, and only approximately 5% of all ischaemic stroke patients in industrialized countries receive this treatment. Studies are currently being carried out to determine whether intravenous alteplase would be safe and effective for up to 4.5 hours after ischaemic stroke onset, and whether it should be followed by an intra-arterial approach. Two novel thrombolytic drugs being studied for acute ischaemic stroke are desmoteplase and tenecteplase. Although the first trials were promising, the most recent evidence suggests that desmoteplase is not superior to placebo, even in carefully selected patients, in the 3- to 9-hour time window after stroke onset. Tenecteplase has only been studied for acute ischaemic stroke in a single noncontrolled, dose-finding trial in the 3-hour time window after stroke onset, which suggested a similar efficacy to that demonstrated in the historical data from the alteplase trials. A trial to compare the safety and efficacy of tenecteplase versus alteplase is ongoing. Safer and more effective thrombolytic drugs for the treatment of ischaemic stroke are thus being sought. Such agents will be welcome, but they are not here yet. While waiting we are likely to see the emergence of additive therapies, including ultrasound insonation, neuroprotective/regenerative agents and invasive intra-arterial techniques. Novel thrombolytic drugs, or other novel therapies, possess great potential to make a difference in the future, but the most urgent priority now is in the organization of stroke treatment in such a way that more patients receive the currently available optimal treatments.
急性缺血性卒中的治疗旨在使闭塞动脉再通，挽救处于危险中的脑组织，从而将神经后遗症降至最低。十年前的努力带来了目前唯一获批用于急性缺血性卒中的药物治疗，即在卒中发作3小时内静脉注射阿替普酶。接受阿替普酶治疗的患者中只有一半实现了再通，在工业化国家，所有缺血性卒中患者中只有约5%接受了这种治疗。目前正在开展研究，以确定静脉注射阿替普酶在缺血性卒中发作后长达4.5小时是否安全有效，以及是否应继以动脉内治疗方法。正在研究用于急性缺血性卒中的两种新型溶栓药物是去氨普酶和替奈普酶。尽管最初的试验很有前景，但最新证据表明，即使在精心挑选的患者中，去氨普酶在卒中发作后3至9小时的时间窗内并不优于安慰剂。替奈普酶仅在一项卒中发作后3小时时间窗内的非对照剂量探索试验中用于急性缺血性卒中研究，结果显示其疗效与阿替普酶试验的历史数据相似。一项比较替奈普酶与阿替普酶安全性和疗效的试验正在进行。因此，正在寻找更安全、更有效的用于治疗缺血性卒中的溶栓药物。这类药物将会受到欢迎，但目前尚未问世。在等待的过程中，我们可能会看到辅助治疗方法的出现，包括超声、神经保护/再生药物和侵入性动脉内技术。新型溶栓药物或其他新型疗法在未来具有产生重大影响的巨大潜力，但目前最紧迫的任务是以让更多患者接受现有最佳治疗的方式来组织卒中治疗。
