美国国立神经病和卒中研究所的研究(NINDS)首次证实，卒中起病3小时内使用重组人组织型纤溶酶原激活物(rt-PA)进行静脉溶栓是治疗急性脑梗死的有效方法。而欧洲急性脑卒中协作组研究(ECASSⅠ和ECASSⅡ)观察起病6小时的静脉rt-PA溶栓未获得阳性结果。虽然NINDS、ECASS和ATLANTIS研究(rt-PA溶栓治疗缺血性脑卒中的非介入疗法)亚组分析发现，脑卒中发病3~4.5小时后rt-PA溶栓可以获得一定效果，但没有直接证据。
德国海德堡大学的维尔纳·哈克(Werner Hacke)教授在本次大会上宣布了ECASSⅢ研究结果。同日，该研究全文在《新英格兰医学杂志》（N Engl J Med 2008， 359(13):1317）同步发表。ECASSⅢ首次直接证实急性脑梗死起病后3~4.5小时给予rt-PA溶栓，可以使患者获益。
值得强调的是，虽然该研究证实脑梗死的溶栓时间窗可以延迟到4.5小时，但这并不意味着医务人员可以将溶栓推迟至发病后4.5小时再进行。正如哈克教授在演讲中指出，溶栓时间窗延长至4.5小时并不是指医生获得了更多的时间，而是为更多的患者争取了溶栓时机。“越早越好”、“时间就是大脑”的基本原则并没有改变，起病1.5小时内溶栓，患者的获益最为突出。ECASSⅢ研究结果也证实了既往汇总分析的结论，起病3~4.5小时溶栓的效益只有1.5小时内溶栓的一半。
原始出处：
NEJM，Volume 359:1317-1329 ，Werner Hacke，Danilo Toni
Thrombolysis with Alteplase 3 to 4.5 Hours after Acute Ischemic Stroke
Werner Hacke, M.D., Markku Kaste, M.D., Erich Bluhmki, Ph.D., Miroslav Brozman, M.D., Antoni Dávalos, M.D., Donata Guidetti, M.D., Vincent Larrue, M.D., Kennedy R. Lees, M.D., Zakaria Medeghri, M.D., Thomas Machnig, M.D., Dietmar Schneider, M.D., Rüdiger von Kummer, M.D., Nils Wahlgren, M.D., Danilo Toni, M.D., for the ECASS Investigators
Background Intravenous thrombolysis with alteplase is the only approved treatment for acute ischemic stroke, but its efficacy and safety when administered more than 3 hours after the onset of symptoms have not been established. We tested the efficacy and safety of alteplase administered between 3 and 4.5 hours after the onset of a stroke.
Methods After exclusion of patients with a brain hemorrhage or major infarction, as detected on a computed tomographic scan, we randomly assigned patients with acute ischemic stroke in a 1:1 double-blind fashion to receive treatment with intravenous alteplase (0.9 mg per kilogram of body weight) or placebo. The primary end point was disability at 90 days, dichotomized as a favorable outcome (a score of 0 or 1 on the modified Rankin scale, which has a range of 0 to 6, with 0 indicating no symptoms at all and 6 indicating death) or an unfavorable outcome (a score of 2 to 6 on the modified Rankin scale). The secondary end point was a global outcome analysis of four neurologic and disability scores combined. Safety end points included death, symptomatic intracranial hemorrhage, and other serious adverse events.
Results We enrolled a total of 821 patients in the study and randomly assigned 418 to the alteplase group and 403 to the placebo group. The median time for the administration of alteplase was 3 hours 59 minutes. More patients had a favorable outcome with alteplase than with placebo (52.4% vs. 45.2%; odds ratio, 1.34; 95% confidence interval [CI], 1.02 to 1.76; P=0.04). In the global analysis, the outcome was also improved with alteplase as compared with placebo (odds ratio, 1.28; 95% CI, 1.00 to 1.65; P<0.05). The incidence of intracranial hemorrhage was higher with alteplase than with placebo (for any intracranial hemorrhage, 27.0% vs. 17.6%; P=0.001; for symptomatic intracranial hemorrhage, 2.4% vs. 0.2%; P=0.008). Mortality did not differ significantly between the alteplase and placebo groups (7.7% and 8.4%, respectively; P=0.68). There was no significant difference in the rate of other serious adverse events.
Conclusions As compared with placebo, intravenous alteplase administered between 3 and 4.5 hours after the onset of symptoms significantly improved clinical outcomes in patients with acute ischemic stroke; alteplase was more frequently associated with symptomatic intracranial hemorrhage.
