替奈普酶与阿替普酶治疗 4.5 小时内急性缺血性脑卒中的随机对照试验的系统评价和荟萃分析。

Tenecteplase vs Alteplase in Acute Ischemic Stroke Within 4.5 Hours: A Systematic Review and Meta-Analysis of Randomized Trials.

机构信息

From the Second Department of Neurology (L.P., A.T., A. Safouris, G. Tsivgoulis), "Attikon" University Hospital, School of Medicine, National and Kapodistrian University of Athens, Greece; Department of Medicine (Neurology) (A.H.K.), McMaster University/Population Health Research Institute, Hamilton, Ontario, Canada; Department of Neurology (Guillaume Turc), GHU Paris Psychiatrie et Neurosciences; Université Paris Cité (G. Turc); INSERM U1266 (G. Turc); FHU NeuroVasc (G. Turc), Paris, France; Department of Primary Education (A.-G.A., D.M.), University of Ioannina, Greece; Department of Neurology and Neurogeriatrics (P.D.S.), Johannes Wesling Klinikum Minden, Ruhr-University Bochum, Germany; Department of Neurology (R.L.), University Hospitals Leuven; Division of Experimental Neurology (R.L.), Department of Neurosciences, KU Leuven-University of Leuven, Belgium; Department of Biotechnological and Applied Clinical Sciences (S.S.), University of L'Aquila, Italy; Stroke Unit (A. Safouris), Metropolitan Hospital, Piraeus, Greece; Department of Neurology (M.K., U.F.), University Hospital Basel, University of Basel, Switzerland; Department of Neurology (A. Sarraj), Case Western Reserve University, University Hospitals Cleveland Medical Center, OH; and Department of Neurology (U.F.), University Hospital Bern, University of Bern, Switzerland.

出版信息

Neurology. 2024 Nov 12;103(9):e209903. doi: 10.1212/WNL.0000000000209903. Epub 2024 Oct 16.

DOI:10.1212/WNL.0000000000209903

PMID:39413337

Abstract

BACKGROUND AND OBJECTIVES

The current European Stroke Organisation expedited recommendation on tenecteplase (TNK) for acute ischemic stroke (AIS) advocates that TNK 0.25 mg/kg can be used alternatively to alteplase (tissue plasminogen activator [TPA]) for AIS of <4.5 hours duration, based on a meta-analytical approach establishing noninferiority. Since the publication of these guidelines, 4 additional randomized controlled clinical trials (RCTs) have provided further insight.

METHODS

We conducted an updated systematic review and meta-analysis including all available RCTs that investigated efficacy and safety of TNK 0.25 mg/kg compared with TPA for the treatment of AIS within 4.5 hours of onset. The primary outcome was defined as the excellent functional outcome at 3 months (modified Rankin Scale [mRS] score 0-1), whereas good functional outcome (mRS score 0-2), reduced disability at 3 months (≥1-point reduction across all mRS scores), symptomatic intracranial hemorrhage (sICH), and 3-month mortality were evaluated as secondary outcomes. Pooled estimates were calculated with random-effects model. A prespecified subgroup analysis was performed stratifying for TNK formulation, that is, original TNK vs biocopy: recombinant human TNK tissue-type plasminogen activator that is available in China and has a different production process.

RESULTS

Eleven RCTs were included comprising a total of 3,788 patients treated with TNK vs 3,757 patients treated with TPA. TNK was associated with higher likelihood of excellent functional outcome (risk ratio [RR] 1.05, 95% CI 1.01-1.10; = 0.012; = 0%; risk difference 2.95%; 95% CI 0.76%-5.14%; = 0.008; = 0%) and reduced disability at 3 months (common odds ratio 1.10, 95% CI 1.01-1.19; = 0.034; = 0%) compared with TPA while good functional outcome (RR 1.03, 95% CI 0.99-1.07; = 0.142; = 28%) was similar between the groups. Regarding safety outcomes, similar rates of sICH (RR 1.12, 95% CI 0.83-1.53; = 0.456; = 0%) and 3-month mortality (RR 0.97, 95% CI 0.82-1.15; = 0.727; = 12%) were observed. When stratified for TNK regimen (original vs biocopy), statistical significance in achieving an excellent functional outcome at 3 months was retained for the original TNK (RR 1.05, 95% CI 1.00-1.10; = 0.044; = 0%).

DISCUSSION

The updated meta-analysis confirms similar safety between TNK 0.25 mg/kg and TPA, while showing that TNK is superior to TPA regarding excellent functional outcome and reduced disability at 3 months. These findings support transitioning to TNK in clinical practice.

摘要

背景与目的

目前欧洲卒中组织推荐使用替奈普酶（TNK）治疗急性缺血性脑卒中（AIS），其依据是一项荟萃分析结果，该分析显示，替奈普酶 0.25mg/kg 与阿替普酶（组织型纤溶酶原激活物 [TPA]）治疗发病 4.5 小时内的 AIS 相比具有非劣效性。自这些指南发布以来，又有 4 项随机对照临床试验（RCT）提供了进一步的见解。

方法

我们进行了一项更新的系统评价和荟萃分析，纳入了所有已发表的 RCT，这些 RCT 评估了替奈普酶 0.25mg/kg 与 TPA 治疗发病 4.5 小时内的 AIS 的疗效和安全性。主要结局定义为 3 个月时的良好功能结局（改良 Rankin 量表 [mRS]评分 0-1），而良好的功能结局（mRS 评分 0-2）、3 个月时残疾程度降低（所有 mRS 评分降低≥1 分）、症状性颅内出血（sICH）和 3 个月死亡率为次要结局。使用随机效应模型计算汇总估计值。对 TNK 制剂进行了预设的亚组分析，即原始 TNK 与生物仿制药：中国可用的重组人 TNK 组织型纤溶酶原激活物，其生产过程不同。

结果

纳入了 11 项 RCT，共纳入 3788 例接受 TNK 治疗的患者和 3757 例接受 TPA 治疗的患者。与 TPA 相比，TNK 更有可能获得良好的功能结局（风险比 [RR]1.05，95%置信区间 [CI]1.01-1.10； = 0.012； = 0%；风险差异 2.95%；95%CI 0.76%-5.14%； = 0.008； = 0%）和 3 个月时残疾程度降低（常见比值比 1.10，95%CI 1.01-1.19； = 0.034； = 0%），而良好的功能结局（RR 1.03，95%CI 0.99-1.07； = 0.142； = 28%）两组之间相似。关于安全性结局，sICH（RR 1.12，95%CI 0.83-1.53； = 0.456； = 0%）和 3 个月死亡率（RR 0.97，95%CI 0.82-1.15； = 0.727； = 12%）的发生率相似。当按 TNK 方案（原始与生物仿制药）分层时，原始 TNK 在 3 个月时达到良好功能结局的统计学意义仍然保留（RR 1.05，95%CI 1.00-1.10； = 0.044； = 0%）。