急性腔隙性缺血性脑卒中患者应用小剂量与标准剂量阿替普酶溶栓治疗的效果对比：ENCHANTED 试验。
Low-Dose vs Standard-Dose Alteplase in Acute Lacunar Ischemic Stroke: The ENCHANTED Trial.
机构信息
From The George Institute for Global Health, Faculty of Medicine (Z.Z., C.D., C.X., S. Yoshimura, C.C., T.T.-Y., A.M., X.C., M.L.H., M.W., J.C., C.S.A.), and South Western Clinical School (M.W.P.), University of New South Wales Sydney, Australia; Department of Radiology (Z.Z., J.X.), Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, China; Department of Neurology (C.D., C.C., C.S.A.), Royal Prince Alfred Hospital, Sydney Health Partners; Sydney Medical School (C.D., C.C.), University of Sydney, Australia; Department of Neurosurgery (C.X.), West China Hospital, Sichuan University, Chengdu, China; Department of Cerebrovascular Medicine (S. Yoshimura, T.T.-Y.), National Cerebral and Cardiovascular Center, Osaka; Department of Neurology and Neuroscience (T.T.-Y.), Nagoya City University Graduate School of Medical Science, Japan; Department of Neurology (S. You), the Second Affiliated Hospital of Soochow University, Suzhou, China; The George Institute for Global Health, School of Public Health (M.W.), Imperial College, London; Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Center (T.G.R.), University of Leicester, UK; Melbourne Brain Centre, Royal Melbourne Hospital University Department of Medicine (M.W.P.), University of Melbourne, Australia; Departments of Clinical Neurosciences and Radiology, Hotchkiss Brain Institute, Cumming School of Medicine (A.M.D.), University of Calgary, Canada; Westmead Applied Research Centre (R.I.L.), University of Sydney, Australia; Division of Neuroimaging Sciences, Edinburgh Imaging and Centre for Clinical Brain Sciences (G.M., J.M.W.), and UK Dementia Research Institute (J.M.W.), University of Edinburgh; and The George Institute China at Peking University Health Science Center (C.S.A.), Beijing, China.
出版信息
Neurology. 2021 Mar 16;96(11):e1512-e1526. doi: 10.1212/WNL.0000000000011598. Epub 2021 Feb 3.
OBJECTIVE
To determine any differential efficacy and safety of low- vs standard-dose IV alteplase for lacunar vs nonlacunar acute ischemic stroke (AIS), we performed post hoc analyzes from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) alteplase dose arm.
METHODS
In a cohort of 3,297 ENCHANTED participants, we identified those with lacunar or nonlacunar AIS with different levels of confidence (definite/according to prespecified definitions based on clinical and adjudicated imaging findings. Logistic regression models were used to determine associations of lacunar AIS with 90-day outcomes (primary, modified Rankin Scale [mRS] scores 2-6; secondary, other mRS scores, intracerebral hemorrhage [ICH], and early neurologic deterioration or death) and treatment effects of low- vs standard-dose alteplase across lacunar and nonlacunar AIS with adjustment for baseline covariables.
RESULTS
Of 2,588 participants with available imaging and clinical data, we classified cases as definite/probable lacunar (n = 490) or nonlacunar AIS (n = 2,098) for primary analyses. Regardless of alteplase dose received, lacunar AIS participants had favorable functional (mRS 2-6, adjusted odds ratio [95% confidence interval] 0.60 [0.47-0.77]) and other clinical or safety outcomes compared to participants with nonlacunar AIS. Low-dose alteplase (versus standard) had no differential effect on functional outcomes (mRS 2-6, 1.04 [0.87-1.24]) but reduced the risk of symptomatic ICH in all included participants. There were no differential treatment effects of low- vs standard-dose alteplase on all outcomes across lacunar and nonlacunar AIS (all ≥0.07).
CONCLUSIONS
We found no evidence from the ENCHANTED trial that low-dose alteplase had any advantages over standard dose for definite/probable lacunar AIS.
CLASSIFICATION OF EVIDENCE
This study provides Class II evidence that for patients with lacunar AIS, low-dose alteplase had no additional benefit or safety over standard-dose alteplase.
CLINICAL TRIAL REGISTRATION
Clinicaltrials.gov identifier NCT01422616.
目的
通过对增强控制高血压和溶栓治疗缺血性卒中介入试验（ENCHANTED）阿替普酶剂量臂的事后分析，确定低剂量与标准剂量 IV 阿替普酶治疗腔隙性与非腔隙性急性缺血性卒中（AIS）的疗效和安全性差异。
方法
在 ENCHANTED 3297 名参与者的队列中，我们根据临床和经裁决的影像学发现的明确/既定定义，确定了腔隙性或非腔隙性 AIS 患者。使用逻辑回归模型确定腔隙性 AIS 与 90 天结局（主要结局，改良 Rankin 量表[mRS]评分 2-6；次要结局，其他 mRS 评分、颅内出血[ICH]和早期神经功能恶化或死亡）以及低剂量与标准剂量阿替普酶治疗腔隙性和非腔隙性 AIS 的治疗效果之间的关联，同时调整了基线协变量。
结果
在有可用影像学和临床数据的 2588 名参与者中，我们将病例分为明确/可能的腔隙性（n=490）或非腔隙性 AIS（n=2098）进行主要分析。无论接受何种阿替普酶剂量，与非腔隙性 AIS 患者相比，腔隙性 AIS 患者的功能结局（mRS 2-6，校正比值比[95%置信区间]0.60[0.47-0.77]）和其他临床或安全性结局均更好。与标准剂量相比，低剂量阿替普酶（versus standard）对功能结局（mRS 2-6）没有差异（1.04[0.87-1.24]），但降低了所有纳入患者的症状性 ICH 风险。在腔隙性和非腔隙性 AIS 中，低剂量与标准剂量阿替普酶在所有结局上均无差异（均≥0.07）。
结论
从 ENCHANTED 试验中，我们没有发现低剂量阿替普酶对明确/可能的腔隙性 AIS 比标准剂量有任何优势。
证据分类
本研究提供了 II 级证据，表明对于腔隙性 AIS 患者，低剂量阿替普酶与标准剂量阿替普酶相比没有额外的获益或安全性。
临床试验注册
ClinicalTrials.gov 标识符 NCT01422616。
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