Department of Neurology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands2Department of Radiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands.
Department of Neurology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands3Department of Radiology, Academic Medical Center, Amsterdam, the Netherlands.
JAMA Neurol. 2016 Feb;73(2):190-6. doi: 10.1001/jamaneurol.2015.3886.
Intra-arterial treatment (IAT) for acute ischemic stroke caused by intracranial arterial occlusion leads to improved functional outcome in patients treated within 6 hours after onset. The influence of treatment delay on treatment effect is not yet known.
To evaluate the influence of time from stroke onset to the start of treatment and from stroke onset to reperfusion on the effect of IAT.
DESIGN, SETTING, AND PARTICIPANTS: The Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN) was a multicenter, randomized clinical open-label trial of IAT vs no IAT in 500 patients. The time to the start of treatment was defined as the time from onset of symptoms to groin puncture (TOG). The time from onset of treatment to reperfusion (TOR) was defined as the time to reopening the vessel occlusion or the end of the procedure in cases for which reperfusion was not achieved. Data were collected from December 3, 2010, to June 3, 2014, and analyzed (intention to treat) from July 1, 2014, to September 19, 2015.
Main outcome was the modified Rankin Scale (mRS) score for functional outcome (range, 0 [no symptoms] to 6 [death]). Multiple ordinal logistic regression analysis estimated the effect of treatment and tested for the interaction of time to randomization, TOG, and TOR with treatment. The effect of treatment as a risk difference on reaching independence (mRS score, 0-2) was computed as a function of TOG and TOR. Calculations were adjusted for age, National Institutes of Health Stroke Scale score, previous stroke, atrial fibrillation, diabetes mellitus, and intracranial arterial terminus occlusion.
Among 500 patients (58% male; median age, 67 years), the median TOG was 260 (interquartile range [IQR], 210-311) minutes; median TOR, 340 (IQR, 274-395) minutes. An interaction between TOR and treatment (P = .04) existed, but not between TOG and treatment (P = .26). The adjusted risk difference (95% CI) was 25.9% (8.3%-44.4%) when reperfusion was reached at 3 hours, 18.8% (6.6%-32.6%) at 4 hours, and 6.7% (0.4%-14.5%) at 6 hours.
For every hour of reperfusion delay, the initially large benefit of IAT decreases; the absolute risk difference for a good outcome is reduced by 6% per hour of delay. Patients with acute ischemic stroke require immediate diagnostic workup and IAT in case of intracranial arterial vessel occlusion.
trialregister.nl Identifier: NTR1804.
重要性：对于由颅内动脉闭塞引起的急性缺血性脑卒中，动脉内治疗（IAT）可改善发病后 6 小时内接受治疗的患者的功能结局。治疗延迟对治疗效果的影响尚不清楚。
目的：评估从发病到开始治疗以及从发病到再灌注的时间对 IAT 效果的影响。
设计、地点和参与者：荷兰多中心急性缺血性脑卒中血管内治疗随机临床试验（MR CLEAN）是一项多中心、随机、开放标签的 IAT 与无 IAT 比较的临床试验，共纳入 500 例患者。治疗开始时间定义为从症状发作到腹股沟穿刺的时间（TOG）。从治疗开始到再灌注的时间（TOR）定义为再通血管闭塞或未再通血管时手术结束的时间。数据于 2010 年 12 月 3 日至 2014 年 6 月 3 日采集，并于 2014 年 7 月 1 日至 2015 年 9 月 19 日进行分析（意向治疗）。
主要结局和测量指标：主要结局为改良 Rankin 量表（mRS）评分（0 分：无症状；6 分：死亡），用于评估功能结局。多变量有序逻辑回归分析评估了治疗的效果，并检验了随机分组时间、TOG 和 TOR 与治疗之间的交互作用。TOG 和 TOR 作为函数，计算了治疗作为风险差异达到独立（mRS 评分，0-2）的效果。计算时对年龄、美国国立卫生研究院卒中量表评分、既往卒中、心房颤动、糖尿病和颅内动脉终末闭塞等因素进行了调整。
结果：在 500 例患者（58%为男性；中位年龄 67 岁）中，TOG 的中位数为 260 分钟（四分位距[IQR]：210-311 分钟），TOR 的中位数为 340 分钟（IQR：274-395 分钟）。TOR 与治疗之间存在交互作用（P =.04），但 TOG 与治疗之间无交互作用（P =.26）。当再灌注时间达到 3 小时时，调整后的风险差异（95%CI）为 25.9%（8.3%-44.4%），4 小时时为 18.8%（6.6%-32.6%），6 小时时为 6.7%（0.4%-14.5%）。
结论和相关性：再灌注每延迟 1 小时，IAT 的最初获益就会减少 1 小时；每小时延迟，获得良好结局的绝对风险差异降低 6%。对于急性缺血性脑卒中患者，一旦怀疑颅内动脉血管闭塞，应立即进行诊断性检查和 IAT。
试验注册：NTR1804，荷兰临床试验注册中心。
