Tenecteplase versus alteplase for the treatment of acute ischemic stroke: a meta-analysis of randomized controlled trials

Tenecteplase, a modified variant of alteplase with greater fibrin specificity and longer plasma half-life, may have better efficacy and safety than alteplase in patients with acute ischemic stroke (AIS). We aimed to compare the benefits and risks of tenecteplase versus alteplase in the treatment of AIS. Electronic databases were searched up to 10 February 2023 for randomized controlled trials evaluating the effect of tenecteplase versus alteplase in the treatment of AIS. The primary outcome was functional outcome at 90 days, and secondary outcomes including the symptomatic intracranial haemorrhage (SICH), and major neurological improvement. Subgroup analysis was performed based on the different dosage of tenecteplase. Ten studies with a total of 5123 patients were analysed in this meta-analysis. Overall, no significant difference between tenecteplase and alteplase was observed for functional outcome at 90 days (excellent: OR 1.08, 95%CI 0.93–1.26, <i>I</i>² = 26%; good: OR 1.04, 95%CI 0.83–1.30, <i>I</i>² = 56%; poor: OR 0.95, 95%CI 0.75–1.21, <i>I</i>² = 31%), SICH (OR 1.12, 95%CI 0.79–1.59, <i>I</i>² = 0%), and early major neurological improvement (OR 1.26, 95%CI 0.80–1.96, <i>I</i>² = 65%). The subgroup analysis suggested that the 0.25 mg/kg dose of tenecteplase had potentially greater efficacy and lower symptomatic intracerebral haemorrhage risk compared with 0.25 mg/kg dose tenecteplase. Among AIS patients, there was no significant difference on clinical outcomes between tenecteplase and alteplase. Subgroup analysis demonstrated that 0.25 mg/kg doses of tenecteplase were more beneficial than 0.4 mg/kg doses of tenecteplase. Further studies are required to identify the optimal dosage of tenecteplase. Randomized controlled trials exploring comparative efficacy and safety of tenecteplase and alteplase have been yielding inconsistent results on various outcomes and merit the conduction of a meta-analysis to adequately answer these questions. Analysis of evidence from randomized studies suggests that tenecteplase is as safe as alteplase for the treatment of acute ischemic stroke and tenecteplase is potentially associated with more favourable outcomes. Tenecteplase at 0.25 mg/kg dose is more efficacious and at least as safe as alteplase for stroke thrombolysis.

替奈普酶（Tenecteplase）是阿替普酶（alteplase）的改造变体，具有更高的纤维蛋白特异性与更长的血浆半衰期，在急性缺血性脑卒中（acute ischemic stroke, AIS）患者中，其疗效与安全性可能优于阿替普酶。本研究旨在比较替奈普酶与阿替普酶治疗急性缺血性脑卒中的获益与风险。我们检索了截至2023年2月10日的电子数据库，纳入评估替奈普酶对比阿替普酶治疗急性缺血性脑卒中效果的随机对照试验。主要结局指标为90天功能结局，次要结局指标包括症状性颅内出血（symptomatic intracranial haemorrhage, SICH）以及神经功能大幅改善情况。本研究基于替奈普酶的不同给药剂量进行亚组分析。本项荟萃分析共纳入10项研究，涉及5123例患者。整体而言，替奈普酶与阿替普酶在90天功能结局[优良：比值比（OR）=1.08，95%置信区间（CI）0.93~1.26，<i>I</i>²=26%；良好：OR=1.04，95%CI 0.83~1.30，<i>I</i>²=56%；较差：OR=0.95，95%CI 0.75~1.21，<i>I</i>²=31%]、症状性颅内出血（OR=1.12，95%CI 0.79~1.59，<i>I</i>²=0%）以及早期神经功能大幅改善（OR=1.26，95%CI 0.80~1.96，<i>I</i>²=65%）方面均未观察到显著差异。亚组分析显示，0.25mg/kg剂量的替奈普酶相较阿替普酶具有更优的疗效与更低的症状性颅内出血风险。在急性缺血性脑卒中患者中，替奈普酶与阿替普酶的临床结局无显著差异。亚组分析显示，0.25mg/kg剂量的替奈普酶获益优于0.4mg/kg剂量的替奈普酶。未来仍需开展进一步研究以明确替奈普酶的最佳给药剂量。针对替奈普酶与阿替普酶疗效及安全性对比的随机对照试验，在不同结局指标上的结果并不一致，因此有必要开展荟萃分析以充分解答该类问题。基于随机对照研究的证据分析显示，替奈普酶治疗急性缺血性脑卒中的安全性与阿替普酶相当，且可能带来更优的临床结局。0.25mg/kg剂量的替奈普酶用于脑卒中溶栓治疗时，疗效更优且安全性至少与阿替普酶相当。