Intravenous thrombolysis in unwitnessed stroke onset: MR WITNESS trial results
Intravenous thrombolysis in unwitnessed stroke onset: MR WITNESS trial results
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DOI：
10.1002/ana.25235
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发表时间：
2018-05-01
影响因子：
11.2
通讯作者：
Warach, Steven
中科院分区：
文献类型：
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作者：
Schwamm, Lee H.;Wu, Ona;Warach, Steven
大多数急性缺血性卒中（AIS）患者在无症状发作的情况下不适合静脉溶栓，原因仅在于时机。液体衰减反转恢复（FLAIR）磁共振成像（MRI）上的病变演变与卒中持续时间相关，弥散加权MRI与FLAIR（qDFM）的定量不匹配可能表明指南推荐的溶栓治疗范围内的卒中持续时间。我们在一项开放标签、2a期前瞻性研究中测试了在发现症状后4.5小时内静脉溶栓对qDFM患者是否安全（NCT 01282242）.方法年龄在18至85岁的AIS患者，自他们最后一次被知道身体健康后4.5至24小时，在14家医院中筛选了在症状发现后4.5小时内可通过静脉注射阿替普酶（0.9 mg/kg）治疗且表现为qDFM的患者。主要结局是预先计划停止规则的症状性颅内出血（sICH）风险。次要结局包括症状性脑水肿风险和90天改良兰金量表（mRS）的功能结局。结果在2011年1月31日至2015年10月4日期间入组了80例受试者，并在距最后一次已知良好的中位11.2小时（IQR=9.5-13.3）时接受阿替普酶治疗。有1例sICH（1.3%）和3例症状性水肿（3.8%）。在90天时，39%的受试者达到了mRS=0-1，48%的受试者进行了血管成像，没有大血管occlusion.InterpretationIntravenous溶栓在4.5小时内的症状发现在qDFM选择的，谁是超出推荐的时间窗，无证中风患者是安全的。使用qDFM测试疗效的随机试验似乎是可行的，并且在没有大血管闭塞的患者中是必要的。神经学年鉴2018;83：980-993
ObjectiveMost acute ischemic stroke (AIS) patients with unwitnessed symptom onset are ineligible for intravenous thrombolysis due to timing alone. Lesion evolution on fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) correlates with stroke duration, and quantitative mismatch of diffusion-weighted MRI with FLAIR (qDFM) might indicate stroke duration within guideline-recommended thrombolysis. We tested whether intravenous thrombolysis 4.5 hours from the time of symptom discovery is safe in patients with qDFM in an open-label, phase 2a, prospective study (NCT01282242).MethodsPatients aged 18 to 85 years with AIS of unwitnessed onset at 4.5 to 24 hours since they were last known to be well, treatable within 4.5 hours of symptom discovery with intravenous alteplase (0.9mg/kg), and presenting with qDFM were screened across 14 hospitals. The primary outcome was the risk of symptomatic intracranial hemorrhage (sICH) with preplanned stopping rules. Secondary outcomes included symptomatic brain edema risk, and functional outcomes of 90-day modified Rankin Scale (mRS).ResultsEighty subjects were enrolled between January 31, 2011 and October 4, 2015 and treated with alteplase at median 11.2 hours (IQR=9.5-13.3) from when they were last known to be well. There was 1 sICH (1.3%) and 3 cases of symptomatic edema (3.8%). At 90 days, 39% of subjects achieved mRS=0-1, as did 48% of subjects who had vessel imaging and were without large vessel occlusions.InterpretationIntravenous thrombolysis within 4.5 hours of symptom discovery in patients with unwitnessed stroke selected by qDFM, who are beyond the recommended time windows, is safe. A randomized trial testing efficacy using qDFM appears feasible and is warranted in patients without large vessel occlusions. Ann Neurol 2018;83:980-993