Department of Emergency Medicine, University of Texas Medical Branch, Galveston, TX.
Department of Emergency Medicine, University of Texas Medical Branch, Galveston, TX.
Ann Emerg Med. 2023 Dec;82(6):720-728. doi: 10.1016/j.annemergmed.2023.03.022. Epub 2023 May 12.
Intravenous thrombolysis with alteplase has been the foundation of initial treatment of acute ischemic stroke for several decades. Tenecteplase is a thrombolytic agent that offers logistical advantages in cost and administration relative to alteplase. There is evidence that tenecteplase has at least similar efficacy and safety outcomes compared with alteplase for stroke. In this study, we compared tenecteplase versus alteplase for acute stroke in a large retrospective US database (TriNetX) regarding the following 3 outcomes: (1) mortality, (2) intracranial hemorrhage, and (3) the need for acute blood transfusions.
In this retrospective study using the US cohort of 54 academic medical centers/health care organizations in the TriNetX database, we identified 3,432 patients treated with tenecteplase and 55,894 patients treated with alteplase for stroke after January 1, 2012. Propensity score matching was performed on basic demographic information and 7 previous clinical diagnostic groups, resulting in a total of 6,864 patients with acute stroke evenly matched between groups. Mortality rates, the frequency of intracranial hemorrhage, and blood transfusions (as a marker of significant blood loss) were recorded for each group over the ensuing 7- and 30-day periods. Secondary subgroup analyses were conducted on a cohort treated from 2021 to 2022 in an attempt to determine whether temporal differences in acute ischemic stroke treatment would alter the results.
Patients treated with tenecteplase had a significantly lower mortality rate (8.2% versus 9.8%; risk ratio [RR], 0.832) and lower risk of major bleeding as measured by the frequency of blood transfusions (0.3% versus 1.4%; RR, 0.207) than alteplase at 30 days after thrombolysis for stroke. In the larger 10-year data set of patients with stroke treated after January 1, 2012, patients receiving tenecteplase were not found to have a statistically different incidence of intracranial hemorrhage (3.5% versus 3.0%; RR, 1.185) at 30 days after the administration of the thrombolytic agents in patients. However, a subgroup analysis of 2,216 evenly matched patients with stroke treated from 2021 to 2022 demonstrated notably better survival and statistically lower rates of intracranial hemorrhage than the alteplase group.
In our large retrospective multicenter study using real-world evidence from large health care organizations, tenecteplase for the treatment of acute stroke demonstrated a lower mortality rate, decreased intracranial hemorrhage, and less significant blood loss. The favorable mortality and safety profiles observed in this large study, taken together with previous randomized controlled trial data and operational advantages in rapid dosing and cost-effectiveness, all support the preferential use of tenecteplase in patients with ischemic stroke.
阿替普酶静脉溶栓已成为急性缺血性脑卒中初始治疗的基石已有数十年。替奈普酶是一种溶栓药物，与阿替普酶相比，在成本和给药方面具有后勤优势。有证据表明，替奈普酶在卒中治疗方面至少具有与阿替普酶相当的疗效和安全性结局。在这项研究中，我们在一个大型的美国回顾性数据库（TriNetX）中比较了替奈普酶和阿替普酶治疗急性脑卒中的效果，这 3 个结局分别为：（1）死亡率，（2）颅内出血，（3）急性输血需求。
在这项使用 TriNetX 数据库中 54 家学术医疗中心/医疗机构的美国队列的回顾性研究中，我们在 2012 年 1 月 1 日之后识别出 3432 例接受替奈普酶治疗和 55894 例接受阿替普酶治疗的脑卒中患者。基于基本人口统计学信息和 7 个既往临床诊断组进行倾向评分匹配，共得到 6864 例急性脑卒中患者，两组之间的人数相当。在接下来的 7 天和 30 天期间，记录每组的死亡率、颅内出血频率和输血情况（作为显著失血的标志物）。对 2021 年至 2022 年期间接受治疗的队列进行了二次亚组分析，试图确定急性缺血性脑卒中治疗的时间差异是否会改变结果。
与阿替普酶相比，接受替奈普酶治疗的患者在脑卒中溶栓治疗后 30 天的死亡率（8.2%比 9.8%；风险比 [RR]，0.832）和输血频率（0.3%比 1.4%；RR，0.207）均显著降低。在 2012 年 1 月 1 日之后接受治疗的、包含所有脑卒中患者的、长达 10 年的更大数据集分析中，我们发现接受替奈普酶治疗的患者在溶栓后 30 天的颅内出血发生率并无统计学差异（3.5%比 3.0%；RR，1.185）。然而，对 2021 年至 2022 年期间接受治疗的 2216 例均衡匹配的脑卒中患者进行的亚组分析显示，与阿替普酶组相比，替奈普酶组的生存率显著提高，颅内出血发生率显著降低。
在我们使用大型医疗机构真实世界证据的大型回顾性多中心研究中，替奈普酶治疗急性脑卒中的死亡率较低，颅内出血较少，失血量较少。在这项大型研究中观察到的有利的死亡率和安全性特征，加上先前的随机对照试验数据和在快速给药方面的操作优势以及成本效益，都支持在缺血性脑卒中患者中优先使用替奈普酶。
