Department of Neurology, Karolinska University Hospital, and Department of Clinical Neurosciences, Karolinska Institutet, Stockholm, Sweden.
Lancet Neurol. 2010 Sep;9(9):866-74. doi: 10.1016/S1474-4422(10)70165-4. Epub 2010 Jul 26.
In September, 2008, the European Acute Stroke Study III (ECASS III) randomised trial and the Safe Implementation of Treatment in Stroke-International Stroke Thrombolysis Registry (SITS-ISTR) observational study reported the efficacy and safety of the extension of the time window for intravenous alteplase treatment from within 3 h to within 4.5 h after stroke onset. We aimed to assess the implementation of the wider time window, its effect on the admission-to-treatment time, and safety and functional outcome in patients recorded in SITS-ISTR.
Patients treated according to the criteria of the European Summary of Product Characteristics, except for the time window, were included. Patients were grouped according to whether they were registered into SITS-ISTR before or after October, 2008. We measured admission-to-treatment time and rates of symptomatic intracerebral haemorrhage, mortality, and functional independence at 3 months.
23 942 patients were included in SITS-ISTR between December, 2002, and February, 2010, of whom 2376 were treated 3-4.5 h after symptom onset. The proportion of patients treated within 3-4.5 h by the end of 2009 was three times higher than in the first three quarters of 2008 (282 of 1293 [22%] vs 67 of 1023 [7%]). The median admission-to-treatment time was 65 min both for patients registered before and after October, 2008 (p=0.94). 352 (2%) of 21 204 patients treated within 3 h and 52 (2%) of 2317 treated within 3-4.5 h of stroke had symptomatic intracerebral haemorrhage at 3 months (adjusted odds ratio [OR] 1.44, 95% CI 1.05-1.97; p=0.02). 2287 (12%) of 18 583 patients who were treated within 3 h and 218 (12%) of 1817 who were treated within 3-4.5 h had died by the 3-month follow-up (adjusted OR 1.26, 95% CI 1.07-1.49; p=0.005); 10 531 (57%) of 18 317 patients treated within 3 h of stroke and 1075 (60%) of 1784 who were treated within 3-4.5 h were functionally independent at 3 months (adjusted OR 0.84, 95% CI 0.75-0.95; p=0.005).
Since October, 2008, thrombolysis within 3-4.5 h after stroke has been implemented rapidly, with a simultaneous increase in the number of patients treated within 3 h; admission-to-treatment time has not increased. Safety and functional outcomes are less favourable after 3 h, but the wider time window now offers an opportunity for treatment of those patients who cannot be treated earlier. Thrombolysis should be initiated within 4.5 h after onset of ischaemic stroke, although every effort should be made to treat patients as early as possible after symptom onset.
Boehringer Ingelheim, Ferrer, the European Union Public Health Executive Authority, and Medical Training and Research (ALF) from Stockholm County Council and Karolinska Institutet.
2008 年 9 月，欧洲急性脑卒中研究 III（ECASS III）随机试验和安全实施溶栓治疗国际脑卒中溶栓登记研究（SITS-ISTR）观察性研究报告了静脉内阿替普酶治疗时间窗从发病后 3 小时内延长至 4.5 小时的疗效和安全性。我们旨在评估更广泛的时间窗的实施情况、对入院至治疗时间的影响以及 SITS-ISTR 记录的患者的安全性和功能结局。
纳入了符合欧洲产品特性摘要标准的患者，但时间窗除外。根据患者在 2008 年 10 月前或后登记入 SITS-ISTR 分为两组。我们测量了入院至治疗时间以及 3 个月时症状性颅内出血、死亡率和功能独立性的发生率。
2002 年 12 月至 2010 年 2 月，SITS-ISTR 共纳入 23942 例患者，其中 2376 例在症状发作后 3-4.5 小时内接受治疗。到 2009 年底，在 3-4.5 小时内接受治疗的患者比例是 2008 年前三个季度的三倍（282/1293[22%]比 67/1023[7%]）。2008 年 10 月前和后登记的患者入院至治疗时间中位数均为 65 分钟（p=0.94）。352 例（2%）在 3 小时内接受治疗的 21204 例患者和 2317 例在 3-4.5 小时内接受治疗的患者在 3 个月时有症状性颅内出血（调整后的比值比[OR]为 1.44，95%CI 为 1.05-1.97；p=0.02）。在 3 小时内接受治疗的 18583 例患者中，有 2287 例（12%）死亡，在 3-4.5 小时内接受治疗的 1817 例患者中，有 218 例（12%）死亡（调整后的 OR 为 1.26，95%CI 为 1.07-1.49；p=0.005）；在 3 小时内接受治疗的 18317 例患者中，有 10531 例（57%）在 3 个月时功能独立，在 3-4.5 小时内接受治疗的 1784 例患者中，有 1075 例（60%）在 3 个月时功能独立（调整后的 OR 为 0.84，95%CI 为 0.75-0.95；p=0.005）。
自 2008 年 10 月以来，3-4.5 小时内的溶栓治疗迅速实施，同时接受治疗的 3 小时内患者数量增加；入院至治疗时间没有增加。3 小时后安全性和功能结局较差，但现在更宽的时间窗为那些不能更早治疗的患者提供了治疗机会。尽管应尽一切努力尽快治疗患者，但应在缺血性脑卒中发作后 4.5 小时内开始溶栓治疗。
勃林格殷格翰、费雷尔、欧盟公共卫生执行局、医疗培训和研究（ALF），来自斯德哥尔摩县议会和卡罗林斯卡学院。
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