Muir Keith W
School of Cardiovascular & Metabolic Health, University of Glasgow, Queen Elizabeth University Hospital, Glasgow, UK.
Int J Stroke. 2025 Mar;20(3):261-267. doi: 10.1177/17474930241307098. Epub 2025 Jan 6.
Recent clinical trials provide robust evidence of non-inferiority of tenecteplase 0.25 mg/kg over alteplase 0.9 mg/kg in acute ischemic stroke treated within 4.5 h of time last known well. Aggregate data meta-analysis suggests likely superiority of tenecteplase with respect to excellent (modified Rankin Scale 0 or 1) outcomes at 90 days. Less complex single intravenous bolus administration of tenecteplase brings significant logistical benefits compared to alteplase. Real-world implementation data demonstrate reduced door-to-needle and door-to-puncture times, and potentially improved clinical outcomes. Avoiding the need for infusion pumps and monitoring reduces resource requirements and facilitates inter-hospital transfer. Guidelines favor tenecteplase over alteplase due to its logistical advantages. Transitioning services to tenecteplase requires consideration of education and training for all relevant staff (medical, nursing, pharmacy) and should address physician concerns. Use of stroke-specific tenecteplase 25 mg dose vials is strongly preferable to minimize the chance of dosing errors that might arise from use of cardiac-dose tenecteplase. Some off-label uses of alteplase are supported by positive randomized controlled trial data (wake-up and unknown onset stroke, and imaging-supported late window use 4.5-9 h after onset) while equivalent data for tenecteplase are less conclusive. Trial data comparing tenecteplase to control give relevant safety data for both wake-up / unknown onset stroke and for late time windows, and some efficacy data favor tenecteplase in a late time window. Given the weight of evidence for biologically similar efficacy and safety of tenecteplase 0.25 mg/kg, and potential for dosing errors, retention of alteplase for off-label indications should not be recommended.
近期的临床试验提供了有力证据,表明在最后一次已知健康状态后的4.5小时内治疗急性缺血性中风时,0.25mg/kg的替奈普酶不劣于0.9mg/kg的阿替普酶。汇总数据的荟萃分析表明,替奈普酶在90天时获得良好(改良Rankin量表评分为0或1)预后方面可能更具优势。与阿替普酶相比,替奈普酶单次静脉推注给药方式更简便,带来了显著的后勤保障优势。真实世界的实施数据显示,替奈普酶缩短了门到针和门到穿刺的时间,并可能改善临床预后。避免使用输液泵和监测减少了资源需求,便于医院间转运。由于其后勤保障优势,指南更倾向于使用替奈普酶而非阿替普酶。将服务转换为使用替奈普酶需要考虑对所有相关工作人员(医疗、护理、药学)进行教育和培训,并应解决医生的担忧。强烈建议使用25mg剂量的中风专用替奈普酶小瓶,以尽量减少因使用心脏剂量替奈普酶可能出现的给药错误。阿替普酶的一些超说明书使用有阳性随机对照试验数据支持(醒后和发病时间不明的中风,以及发病后4.5 - 9小时影像学支持的晚期窗口使用),而替奈普酶的等效数据则不太确凿。比较替奈普酶与对照组的试验数据给出了醒后/发病时间不明的中风以及晚期时间窗的相关安全性数据,一些疗效数据表明替奈普酶在晚期时间窗更具优势。鉴于有大量证据表明0.25mg/kg的替奈普酶在生物学上具有相似的疗效和安全性,且存在给药错误的可能性,不建议保留阿替普酶用于超说明书适应症。