BACKGROUND AND OBJECTIVES Randomized trials have proven the benefit of endovascular therapy (EVT) for acute large ischemic stroke. This study was to characterize the effect of time to treatment on benefit of EVT vs medical management (MM) among patients with large ischemic stroke. METHODS This was a post hoc analysis of the Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients with a Large Infarct Core randomized trial. Patients who had an Alberta Stroke Program Early Computed Tomography Score of 3-5 or an ischemic core volume of 70-100 mL within 24 hours of symptom onset were treated with EVT plus MM or MM. Onset-to-expected arterial puncture time (OPT) was analyzed as a categorical variable (<6, 6-<12, and 12-24 hours) using binary logistic regression and as a continuous variable using a multivariable fractional polynomial interaction. The primary efficacy outcome was favorable outcomes (modified Rankin Scale scores 0-3) at 90 days. Safety outcomes included any intracranial hemorrhage (ICH), symptomatic ICH, and mortality. RESULTS Among 451 patients (median age 68 years; 61.4% were men; median OPT 487 minutes [interquartile range 328-802]), 226 patients received EVT and 225 patients received MM. The EVT group showed higher rates of favorable outcomes than the MM group within OPT of 6 hours (44.4% vs 29.9%, adjusted odds ratio [aOR] 2.78, 95% CI 1.22-6.32) and 6-12 hours (45.7% vs 29.6%, aOR 2.39 [95% CI 1.21-4.71]), but not in OPT beyond 12 hours (51.6% vs 41.4%, aOR 2.05 [95% CI 0.88-4.77]). The benefit became nonsignificant after OPT of 13 hours and 22 minutes. In 3 OPT intervals, the rates of symptomatic ICH and mortality were similar between EVT and MM although the rate of any ICH increased. However, no interaction effect was found (all p interactions >0.10). DISCUSSION These findings strengthen the benefit of EVT initiated within 13 hours and 22 minutes after symptom onset compared with MM alone in patients with large ischemic stroke, but EVT should not be withheld for patients presenting beyond 13 hours and 22 minutes. Pooled analysis of larger sample sizes is needed. TRIAL REGISTRATION INFORMATION ClinicalTrials.gov; NCT04551664. CLASSIFICATION OF EVIDENCE This study provides Class II evidence that EVT is associated with improved functional outcomes for acute large ischemic stroke within 24 hours after last known well, with no interaction by time.

中文翻译：

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大面积缺血性卒中患者治疗时间与血管内治疗与药物治疗结果之间的关联。


背景和目标 随机试验已证明血管内治疗 （EVT） 对急性大缺血性卒中有益。本研究旨在描述治疗时间对大缺血性卒中患者 EVT 与医疗管理 （MM） 益处的影响。方法 这是对急性前循环大血管闭塞患者伴大梗死核心随机试验的血管内治疗的事后分析。症状出现后 24 小时内 Alberta Stroke Program 早期计算机断层扫描评分为 3-5 或缺血核心体积为 70-100 mL 的患者接受 EVT 加 MM 或 MM 治疗。使用二元 logistic 回归将起始至预期动脉穿刺时间 （OPT） 分析为分类变量 （<6、6-<12 和 12-24 小时），并使用多变量分数多项式交互作用分析为连续变量。主要疗效结局是 90 天时的良好结局 （改良 Rankin 量表评分 0-3）。安全性结局包括任何颅内出血 （ICH） 、症状性 ICH 和死亡率。结果 在 451 例患者 （中位年龄 68 岁;61.4% 为男性;中位 OPT 487 分钟 [四分位距 328-802]）中，226 例患者接受 EVT，225 例患者接受 MM。EVT 组在 OPT 6 小时 （44.4% vs 29.9%，调整比值比 [aOR] 2.78,95% CI 1.22-6.32） 和 6-12 小时（45.7% vs 29.6%，aOR 2.39 [95% CI 1.21-4.71]） 内显示出比 MM 组更高的良好结局率，但在 OPT 超过 12 小时时没有 （51.6% vs 41.4%，aOR 2.05 [95% CI 0.88-4.77]）。OPT 13 小时 22 分钟后，益处变得不显著。在 3 个 OPT 间隔中，EVT 和 MM 之间的症状性 ICH 发生率和死亡率相似，尽管任何 ICH 的发生率都有所增加。 然而，未发现交互效应 （所有 p 交互作用 >0.10）。讨论 这些发现加强了在症状出现后 13 小时 22 分钟内开始 EVT 与单独使用 MM 相比，在大缺血性卒中患者中的益处，但对于就诊超过 13 小时 22 分钟的患者，不应停止 EVT。需要对更大的样本量进行汇总分析。试验注册信息 ClinicalTrials.gov;NCT04551664。证据分类 本研究提供了 II 类证据，表明 EVT 与最后一次已知后 24 小时内急性大缺血性卒中的功能结局改善相关，没有时间相互作用。