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替奈普酶与阿替普酶治疗急性缺血性脑卒中的比较:随机临床试验的成对和网络荟萃分析。

Tenecteplase versus alteplase for management of acute ischemic stroke: a pairwise and network meta-analysis of randomized clinical trials.

机构信息

Department of Internal Medicine, Hurley Medical Center/Michigan State University, Flint, MI, 48503, USA.

, Flint, MI, 48503, USA.

出版信息

J Thromb Thrombolysis. 2018 Nov;46(4):440-450. doi: 10.1007/s11239-018-1721-3.

DOI:10.1007/s11239-018-1721-3
PMID:30117036
Abstract

Tenecteplase is a genetically mutated variant of alteplase with superior pharmacodynamic and pharmacokinetic properties. However, its efficacy and safety in acute ischemic strokes are limited. Hence, we conducted a study to evaluate the efficacy and safety of tenecteplase compared with alteplase in acute ischemic stroke. Electronic databases were searched for randomized clinical trials (RCTs) comparing tenecteplase with alteplase in acute ischemic stroke patients eligible for thrombolysis. We evaluated various efficacy and safety outcomes using random-effects models for both pairwise and Bayesian network meta-analyses along with meta-regression analyses. We included 5 RCTs with a total of 1585 patients. Compared with alteplase, tenecteplase treatment was associated with significantly greater complete recanalization (odd ratio [OR] 2.01; 95% confidence interval [CI] 1.04-3.87; p = 0.04) and early neurological improvement (OR 1.43; 95% CI 1.01-2.03; p = 0.05). There were no differences between the two thrombolytics in terms of excellent recovery (modified Rankin Scale [mRS] 0-1; OR 1.17; 95% CI 0.95-1.44; p = 0.13), functional independence (mRS 0-2; OR 1.24; 95% CI 0.78-1.98), poor recovery (mRS 4-6; OR 0.78; 95% CI 0.49-1.25; p = 0.31), complete/partial recanalization (OR 1.51; 95% CI 0.70-3.26; p = 0.30), any intracerebral hemorrhage (OR 0.81; 95% CI 0.56-1.17; p = 0.26), symptomatic intracerebral hemorrhage (OR 0.98; 95% CI 0.52-1.83; p = 0.94), or mortality (OR 0.83; 95% CI 0.54-1.26; p = 0.38). In network meta-analysis, there were better efficacy and imaging-based outcomes with tenecteplase 0.25 mg/kg without increased risk of safety outcomes. Our results demonstrate that in acute ischemic stroke, thrombolysis with tenecteplase is at least as effective and safe as alteplase.

摘要

替奈普酶是组织型纤溶酶原激活剂的基因变异体,具有更好的药效动力学和药代动力学特性。然而,其在急性缺血性脑卒中中的疗效和安全性有限。因此,我们进行了一项研究,以评估替奈普酶与组织型纤溶酶原激活剂在急性缺血性脑卒中患者中的疗效和安全性。我们检索了电子数据库中比较适合溶栓治疗的急性缺血性脑卒中患者中使用替奈普酶与组织型纤溶酶原激活剂的随机临床试验(RCT)。我们使用随机效应模型对直接和贝叶斯网络荟萃分析以及荟萃回归分析中的各种疗效和安全性结局进行了评估。我们纳入了 5 项 RCT,共纳入了 1585 名患者。与组织型纤溶酶原激活剂相比,替奈普酶治疗与更高的完全再通率(比值比[OR] 2.01;95%置信区间[CI] 1.04-3.87;p=0.04)和早期神经功能改善(OR 1.43;95% CI 1.01-2.03;p=0.05)相关。两种溶栓药物在良好恢复(改良 Rankin 量表[ mRS ] 0-1;OR 1.17;95% CI 0.95-1.44;p=0.13)、功能独立性(mRS 0-2;OR 1.24;95% CI 0.78-1.98)、恢复不良(mRS 4-6;OR 0.78;95% CI 0.49-1.25;p=0.31)、完全/部分再通率(OR 1.51;95% CI 0.70-3.26;p=0.30)、任何颅内出血(OR 0.81;95% CI 0.56-1.17;p=0.26)、症状性颅内出血(OR 0.98;95% CI 0.52-1.83;p=0.94)或死亡率(OR 0.83;95% CI 0.54-1.26;p=0.38)方面无差异。网络荟萃分析显示,替奈普酶 0.25mg/kg 具有更好的疗效和影像学结局,且安全性结局无增加。我们的结果表明,在急性缺血性脑卒中中,替奈普酶溶栓与组织型纤溶酶原激活剂一样有效且安全。

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Tenecteplase versus alteplase for management of acute ischaemic stroke (NOR-TEST): a phase 3, randomised, open-label, blinded endpoint trial.替奈普酶与阿替普酶治疗急性缺血性脑卒中的比较(NOR-TEST):一项 3 期、随机、开放标签、盲终点试验。
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