From Edinburgh Imaging, and UK Dementia Research Institute at the University of Edinburgh and Centre for Clinical Brain Sciences (G.M., Z.M., A.J.F., J.M.W.), and Division of Clinical Neurosciences (P.A.G.S.), University of Edinburgh, UK; Department of Neuroradiology (R.v.K.), Dresden University Stroke Centre, Germany; Danderyd Hospital (A.v.H.), Stockholm, Sweden; Neuroradiology (N.B.), James Cook University Hospital, Middlesborough, UK; School of Medicine (L.C.), University of Western Australia; Cliniques Universitaires St Luc (A.P.), Neurologie, Belgium; Stroke Center (A.A.), Department of Neurology, IRCCS Sacro Cuore Don Calabria Hospital, Negrar, Verona, Italy; Department of Neuroradiology (G.P.), Salford Royal NHS Foundation Trust, Manchester, UK; and Westmead Hospital Clinical School and The George Institute for Global Health (R.I.L.), University of Sydney, Australia.
Neurology. 2018 Nov 27;91(22):e2067-e2077. doi: 10.1212/WNL.0000000000006575. Epub 2018 Oct 26.
To determine whether alteplase alters the development of ischemic lesions on brain imaging after stroke.
The Third International Stroke Trial (IST-3) was a randomized controlled trial of IV alteplase for ischemic stroke. We assessed CT or brain MRI at baseline (pretreatment) and 24 to 48 hours posttreatment for acute lesion visibility, extent, and swelling, masked to all other data. We analyzed associations between treatment allocation, change in brain tissue appearances between baseline and follow-up imaging, and 6-month functional outcome in IST-3. We performed a meta-analysis of randomized trials of alteplase vs control with pre- and postrandomization imaging.
Of 3,035 patients recruited in IST-3, 2,916 had baseline and follow-up brain imaging. Progression in either lesion extent or swelling independently predicted poorer 6-month outcome (adjusted odds ratio [OR] = 0.92, 95% confidence interval [CI] 0.88-0.96, < 0.001; OR = 0.73, 95% CI 0.66-0.79, < 0.001, respectively). Patients allocated alteplase were less likely than controls to develop increased lesion visibility at follow-up (OR = 0.77, 95% CI 0.67-0.89, < 0.001), but there was no evidence that alteplase reduced progression of lesion extent or swelling. In meta-analysis of 6 trials including IST-3 (n = 4,757), allocation to alteplase was associated with a reduction in ischemic lesion extent on follow-up imaging (OR = 0.85, 95% CI 0.76-0.95, = 0.004).
Alteplase was associated with reduced short-term progression in lesion visibility. In meta-analysis, alteplase reduced lesion extent. These findings may indicate that alteplase improves functional outcome by reducing tissue damage.
This study provides Class II evidence that IV alteplase impedes the progression of ischemic brain lesions on imaging after stroke.
确定阿替普酶是否会改变中风后脑影像学上的缺血性病灶发展。
第三次国际中风试验（IST-3）是一项随机对照试验，评估了 IV 阿替普酶治疗缺血性中风的效果。我们对基线（治疗前）和治疗后 24 至 48 小时的 CT 或脑部 MRI 进行评估，以评估急性病灶的可见性、范围和肿胀情况，评估结果对其他所有数据均设盲。我们分析了 IST-3 中治疗分配、基线和随访影像学之间的脑组织外观变化以及 6 个月功能结局之间的关联。我们对阿替普酶与对照组的随机试验进行了荟萃分析，这些试验在随机分组前后均进行了影像学检查。
在 IST-3 中招募的 3035 名患者中，2916 名患者有基线和随访的脑部影像学资料。病变范围或肿胀的进展独立预测了 6 个月的预后较差（调整后的优势比 [OR] = 0.92，95%置信区间 [CI] 0.88-0.96，<0.001；OR = 0.73，95%CI 0.66-0.79，<0.001）。与对照组相比，接受阿替普酶治疗的患者在随访时更不可能出现病灶可见性增加（OR = 0.77，95%CI 0.67-0.89，<0.001），但没有证据表明阿替普酶能减少病灶范围或肿胀的进展。在包括 IST-3 在内的 6 项试验的荟萃分析中（n = 4757），阿替普酶治疗与随访时的缺血性病灶范围缩小相关（OR = 0.85，95%CI 0.76-0.95，= 0.004）。
阿替普酶与病灶可见性的短期进展减少有关。荟萃分析表明，阿替普酶通过减少组织损伤来改善功能结局。
本研究提供了 II 级证据，表明 IV 阿替普酶可阻止中风后脑影像学上的缺血性脑损伤进展。
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