Kaste M
Department of Neurology, University of Helsinki, Finland.
Cerebrovasc Dis. 2001;11 Suppl 1:55-9. doi: 10.1159/000049126.
THROMBOLYSIS: ECASS I, the NINDS trial and ECASS II showed that thrombolysis with rt-PA is effective in acute ischaemic stroke. In ECASS I, there was a safety problem because of increased mortality, while the results of the NINDS trial led the FDA to approve the use of rt-PA in ischaemic stroke. The safety was no more a problem in ECASS II. A meta-analysis of those three trials revealed that thrombolysis decreases the risk of death and dependency. For each 1,000 patients treated within 3 h, there will be 140 less dead or dependent, and 90 less if the treatment is given within 6 h. These data support the view that rt-PA should be part of the management of acute ischaemic stroke within 3 h, and probably beyond, in selected patients and experienced centres. Thrombolysis within a 3-hour time frame is also likely to result in net cost savings.
All trials studying neuroprotecting agents have failed in man, although they have been successful in experimental animals. A combination of thrombolysis and a neuroprotecting agent or a combination of two neuroprotecting agents have been effective in experimental stroke, but the only clinical study with combination therapy (rt-PA with or without lubeluzole) was terminated prematurely before the planned population was enrolled. This was not because of safety problems but because the sponsor lost interest.
In future, there will most likely be others to challenge the strategy of the combined therapy, and this strategy will sooner or later lead to a benchmark breakthrough. It is unlikely that any of these therapies or their combinations will work without well-organised services, which can provide fast and efficient medical care. Without such a triage, any drug will be unlikely to have a major impact on stroke recovery.
溶栓治疗：欧洲急性卒中协作研究I（ECASS I）、美国国立神经疾病与卒中研究所（NINDS）试验以及ECASS II表明，使用重组组织型纤溶酶原激活剂（rt-PA）进行溶栓治疗对急性缺血性卒中有效。在ECASS I中，由于死亡率增加存在安全问题，而NINDS试验的结果促使美国食品药品监督管理局（FDA）批准在缺血性卒中中使用rt-PA。在ECASS II中，安全问题不再存在。对这三项试验的荟萃分析显示，溶栓治疗可降低死亡和依赖风险。每1000例在3小时内接受治疗的患者中，死亡或依赖人数将减少140例；如果在6小时内进行治疗，减少人数为90例。这些数据支持这样的观点，即rt-PA应成为3小时内急性缺血性卒中治疗的一部分，在选定的患者和经验丰富的中心，可能在3小时之后也适用。在3小时时间范围内进行溶栓治疗也可能带来净成本节约。
所有研究神经保护剂的试验在人体中均未成功，尽管在实验动物中取得了成功。溶栓与神经保护剂联合或两种神经保护剂联合在实验性卒中中有效，但唯一一项联合治疗（rt-PA联合或不联合鲁贝唑）的临床研究在计划纳入的人群招募之前就提前终止了。这并非因为安全问题，而是因为赞助商失去了兴趣。
未来，很可能会有其他人挑战联合治疗策略，而且这种策略迟早会带来基准性突破。如果没有组织良好的服务来提供快速有效的医疗护理，这些治疗方法或其组合中的任何一种都不太可能起作用。没有这样的分诊，任何药物都不太可能对卒中恢复产生重大影响。
