Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
China National Clinical Research Center for Neurological Diseases, Beijing, China.
Stroke Vasc Neurol. 2024 Aug 27;9(4):360-366. doi: 10.1136/svn-2023-002396.
Tenecteplase (TNK) was found non-inferior to alteplase in recent clinical trials. We aimed to elucidate the efficacy and safety of TNK versus alteplase for acute ischaemic stroke (AIS).
Systematic literature search and a meta-analysis of phase III clinical trials in ischaemic stroke patients with TNK use were conducted. The primary outcome was excellent functional outcome which was defined as modified Rankin Scale score of 0-1 at 90 days and safety outcomes included symptomatic intracerebral haemorrhage and death at 90 days. We used random-effects model to estimate the pooled risk difference and 95% CI in R package 'Meta'. The included trials were adapted to the non-inferiority analysis with a margin of -4%.
Three trials enrolling 4094 patients were identified by systematic search. All trials included AIS patients within 4.5 hours time window. Meta-analysis indicated that 1089 (53.0%) of 2056 patients in the TNK arm and 1016 (50.5%) of 2012 in the alteplase arm had excellent functional outcome at 90 days (0.03 (95% CI -0.00 to 0.06); I=0%), meeting the prespecified non-inferiority threshold. And TNK thrombolysis was not correlated with increased risk of symptomatic intracerebral haemorrhage (0.00 (95% CI -0.01 to 0.01); I=0%) or death (0.01 (95% CI -0.01 to 0.02); I=0%) at 90 days. The sensitivity analysis with the 0.25 mg/kg trials exclusively showed similar results to the main analysis.
TNK was non-inferior to alteplase for achieving excellent functional outcome at 90 days without increasing the safety concern in treating patients with AIS. These findings suggest that TNK can be an alternative to alteplase.
CRD42022354342.
替奈普酶（TNK）在最近的临床试验中被证明不劣于阿替普酶。我们旨在阐明 TNK 与阿替普酶治疗急性缺血性脑卒中（AIS）的疗效和安全性。
系统地检索了使用 TNK 的缺血性脑卒中患者的 III 期临床试验文献，并进行了荟萃分析。主要结局为 90 天时改良 Rankin 量表评分 0-1 的优秀功能结局，安全性结局包括 90 天时症状性颅内出血和死亡。我们使用 R 包“Meta”中的随机效应模型来估计汇总风险差异和 95%置信区间。纳入的试验采用 -4%的边界进行非劣效性分析。
通过系统搜索确定了三项纳入 4094 例患者的试验。所有试验均纳入了 4.5 小时时间窗内的 AIS 患者。荟萃分析表明，TNK 组 2056 例患者中有 1089 例（53.0%）和阿替普酶组 2012 例患者中有 1016 例（50.5%）在 90 天时具有优秀的功能结局（0.03（95%CI-0.00 至 0.06）；I=0%），符合预设的非劣效性阈值。并且 TNK 溶栓与症状性颅内出血的风险增加无关（0.00（95%CI-0.01 至 0.01）；I=0%）或 90 天时的死亡（0.01（95%CI-0.01 至 0.02）；I=0%）。仅对 0.25mg/kg 试验进行的敏感性分析显示与主要分析相似的结果。
TNK 在 90 天时达到优秀功能结局的效果不劣于阿替普酶，且在治疗 AIS 患者时不会增加安全性问题。这些发现表明 TNK 可以作为阿替普酶的替代药物。
PROSPERO 注册号：CRD42022354342。
