Department of Neurology, David Geffen School of Medicine, University of California Los Angeles (K.T.M., D.S.L., J.L.S.).
Departments of Emergency Medicine, Neurosurgery/Neurocritical Care, and Neurology, University of Cincinnati College of Medicine, University of Cincinnati, OH (J.B.B.).
Stroke. 2022 Jun;53(6):2069-2074. doi: 10.1161/STROKEAHA.121.038153. Epub 2022 May 11.
Cumulative fragility index (FI) analysis enables quantification of the evidential strength of intravenous alteplase's core indication-treatment of disabling acute ischemic stroke within 3 hours of onset.
Meta-analyses were performed (study level) or identified (individual participant level) for freedom-from-disability (modified Rankin Scale [mRS] score 0-1, primary efficacy), functional independence (mRS score 0-2, secondary efficacy), and mortality outcomes. Individual trial and cumulative FI analyses were serially conducted after each successive randomized controlled trial (RCT). FI scores were classified as follows: not robust (FI 0-4), somewhat robust (FI 5-12), robust (FI 13-33), and highly robust (FI >33).
Nine randomized controlled trials were identified from 1995 to 2021 of within-3-hour intravenous alteplase for acute ischemic stroke. In study-level meta-analyses, alteplase increased freedom-from-disability outcome (mRS score 0-1), 31.0% versus 22.3%, relative risk, 1.39 (95% CI, 1.20-1.61); <0.00001; increased functional independence (mRS score 0-2), 39.7% versus 31.2%, relative risk, 1.29 (95% CI, 1.14-1.45), <0.000; and did not alter mortality, 24.1% versus 26.1%; =0.23. Overall FIs for study-level meta-analyses were both highly robust at 42 and 40 for mRS score 0-1 and mRS score 0-2, respectively. Serial FI analyses showed robust evidential strength for intravenous alteplase superiority with publication of the 2 NINDS-tPA trials (National Institute of Neurological Disorders and Stroke-tissue-type plasminogen activator) in 1995, increased to highly robust in 2012, and remains highly robust in 2021.
Within-3-hour intravenous alteplase for acute ischemic stroke is one of the most robustly proven therapies in medicine. The initial concurrent trials 25 years ago showed robust evidence for benefit and, after additional studies, advanced to highly robust.
累积脆弱指数（FI）分析能够定量评估静脉注射阿替普酶治疗发病 3 小时内的致残性急性缺血性脑卒中的证据强度。
对无残疾（改良 Rankin 量表 [mRS]评分 0-1，主要疗效）、功能独立性（mRS 评分 0-2，次要疗效）和死亡率结局进行了荟萃分析（研究水平）或识别（个体参与者水平）。在每项连续的随机对照试验（RCT）后，分别进行了个体试验和累积 FI 分析。FI 评分如下分类：不稳健（FI 0-4）、有些稳健（FI 5-12）、稳健（FI 13-33）和高度稳健（FI＞33）。
1995 年至 2021 年间，共确定了 9 项发病 3 小时内静脉内阿替普酶治疗急性缺血性脑卒中的 RCT。在研究水平的荟萃分析中，阿替普酶增加了无残疾结局（mRS 评分 0-1），31.0%比 22.3%，相对风险 1.39（95%CI，1.20-1.61）；＜0.00001；增加了功能独立性（mRS 评分 0-2），39.7%比 31.2%，相对风险 1.29（95%CI，1.14-1.45）；＜0.000；且不改变死亡率，24.1%比 26.1%；=0.23。研究水平荟萃分析的整体 FI 均高度稳健，mRS 评分 0-1 和 mRS 评分 0-2 分别为 42 和 40。连续的 FI 分析显示，静脉内阿替普酶的优势具有稳健的证据强度，1995 年发表了 2 项 NINDS-tPA 试验（美国国立神经病学与卒中研究所-组织型纤溶酶原激活剂），2012 年增加到高度稳健，2021 年仍然高度稳健。
发病 3 小时内静脉内注射阿替普酶治疗急性缺血性脑卒中是医学上最有力的治疗方法之一。25 年前的初始平行试验显示出了获益的有力证据，并且在进行了更多的研究后，其稳健性进一步提高到高度稳健。
