MRI-Guided Thrombolysis for Stroke with Unknown Time of Onset
MRI-Guided Thrombolysis for Stroke with Unknown Time of Onset
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DOI：
10.1056/nejmoa1804355
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发表时间：
2018-08-16
影响因子：
158.5
通讯作者：
Gerloff, C.
中科院分区：
文献类型：
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作者：
Thomalla, G.;Simonsen, C. Z.;Gerloff, C.
根据目前的指南，静脉溶栓仅用于治疗急性卒中，如果可以确定症状发作的时间小于4.5小时。我们试图确定是否有一个未知的发病时间和功能提示最近脑梗死的磁共振成像（MRI）的患者将受益于溶栓与使用静脉阿替普酶。METHODS在一项多中心试验中，我们随机分配的患者谁有一个未知的发病时间中风接受静脉阿替普酶或安慰剂。所有患者在MRI弥散加权成像上均可见缺血性病变，但在液体衰减反转恢复（FLAIR）上无实质高信号，这表明卒中发生在大约4.5小时内。我们排除了计划进行血栓切除术的患者。主要终点是良好的结局，定义为90天时改良兰金神经功能障碍量表评分为0或1分（范围为0分[无症状]至6分[死亡]）。次要结果是阿替普酶可能导致改良兰金量表的序数评分低于安慰剂（变化分析）。由于在预期的800例患者中招募了503例后停止了资金，试验提前停止。在这些患者中，254例随机分配接受阿替普酶治疗，249例接受安慰剂治疗。阿替普酶组131/246例患者（53.3%）和安慰剂组102/244例患者（41.8%）报告了90天时的有利结局（校正比值比，1.61; 95%置信区间[CI]，1.09 - 2.36; P = 0.02）。阿替普酶组90天时改良兰金量表的中位评分为1分，安慰剂组为2分（校正后的共同比值比，1.62; 95% CI，1.17 - 2.23; P = 0.003）。阿替普酶组有10例死亡（4.1%），安慰剂组有3例死亡（1.2%）（比值比，3.38; 95% CI，0.92 - 12.52; P = 0.07）。阿替普酶组症状性颅内出血的发生率为2.0%，安慰剂组为0.4（比值比为4.95; 95% CI为0.57 ~ 42.87; P = 0.15）。结论在发病时间未知的急性卒中患者中，通过扩散-在缺血区域的加权成像和FLAIR导致了90天时比安慰剂显著更好的功能结果和更多的颅内出血。（由欧洲联盟第七框架方案供资;
BACKGROUNDUnder current guidelines, intravenous thrombolysis is used to treat acute stroke only if it can be ascertained that the time since the onset of symptoms was less than 4.5 hours. We sought to determine whether patients with stroke with an unknown time of onset and features suggesting recent cerebral infarction on magnetic resonance imaging (MRI) would benefit from thrombolysis with the use of intravenous alteplase.METHODSIn a multicenter trial, we randomly assigned patients who had an unknown time of onset of stroke to receive either intravenous alteplase or placebo. All the patients had an ischemic lesion that was visible on MRI diffusion-weighted imaging but no parenchymal hyperintensity on fluid-attenuated inversion recovery (FLAIR), which indicated that the stroke had occurred approximately within the previous 4.5 hours. We excluded patients for whom thrombectomy was planned. The primary end point was favorable outcome, as defined by a score of 0 or 1 on the modified Rankin scale of neurologic disability (which ranges from 0 [no symptoms] to 6 [death]) at 90 days. A secondary outcome was the likelihood that alteplase would lead to lower ordinal scores on the modified Rankin scale than would placebo (shift analysis).RESULTSThe trial was stopped early owing to cessation of funding after the enrollment of 503 of an anticipated 800 patients. Of these patients, 254 were randomly assigned to receive alteplase and 249 to receive placebo. A favorable outcome at 90 days was reported in 131 of 246 patients (53.3%) in the alteplase group and in 102 of 244 patients (41.8%) in the placebo group (adjusted odds ratio, 1.61; 95% confidence interval [CI], 1.09 to 2.36; P = 0.02). The median score on the modified Rankin scale at 90 days was 1 in the alteplase group and 2 in the placebo group (adjusted common odds ratio, 1.62; 95% CI, 1.17 to 2.23; P = 0.003). There were 10 deaths (4.1%) in the alteplase group and 3 (1.2%) in the placebo group (odds ratio, 3.38; 95% CI, 0.92 to 12.52; P = 0.07). The rate of symptomatic intracranial hemorrhage was 2.0% in the alteplase group and 0.4% in the placebo group (odds ratio, 4.95; 95% CI, 0.57 to 42.87; P = 0.15).CONCLUSIONSIn patients with acute stroke with an unknown time of onset, intravenous alteplase guided by a mismatch between diffusion- weighted imaging and FLAIR in the region of ischemia resulted in a significantly better functional outcome and numerically more intracranial hemorrhages than placebo at 90 days. (Funded by the European Union Seventh Framework Program;