肾功能损害对接受静脉注射替奈普酶和阿替普酶治疗的急性缺血性卒中患者结局的影响：TRACE-2试验的事后分析

Influence of impaired renal function on the outcomes of patients with acute ischaemic stroke treated with intravenous tenecteplase and alteplase: a post hoc analysis of the TRACE-2 trial.

作者信息

Wu Yu, Pan Yuesong, Wang Mengxing, Meng Xia, Wang Yilong, Li Shuya, Wang Yongjun, Zhou Yilun, Du Wanliang

机构信息

Department of Nephrology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

出版信息

Stroke Vasc Neurol. 2025 Mar 18. doi: 10.1136/svn-2024-003726.

DOI:10.1136/svn-2024-003726

PMID:40102020

Abstract

OBJECTIVE

Limited evidence is available regarding the risk-benefit ratio of thrombolytic therapy in patients with stroke and renal impairment complications, particularly for the drug tenecteplase. Therefore, we examined the association of impaired renal function with the safety and efficacy of intravenous thrombolytic treatment (IVT) in patients with acute ischaemic stroke (AIS).

METHODS

A post hoc analysis of a randomised controlled trial (ClinicalTrials gov. NCT04797013) was conducted. Participants who received IVT with tenecteplase and alteplase (0.25 and 0.9 mg/kg, respectively) within 4.5 hours of symptoms onset were categorised based on their estimated glomerular filtration rate as follows: (1) ≥90 mL/min/1.73 m,normal renal function; (2) 60-89 mL/min/1.73 m, mildly decreased renal function; and (3) <60 mL/min/1.73 m, moderately to severely decreased renal function. Patients stratified based on the normal renal function were used as the references. The primary efficacy and safety outcome were the percentage of patients achieving a modified Rankin Scale score of 0-1 at 90 days and the symptomatic intracranial haemorrhage (sICH) occurrence within 36 hours, respectively.

RESULTS

In intravenous tenecteplase-treated patients, mildly decreased renal function (OR 3.10; 95% CI: 1.41 to 6.78) and moderately to severely decreased renal function (OR: 8.03; 95% CI: 2.76 to 23.38) showed an association with a higher risk of all-cause mortality but not with sICH incidence compared with normal renal function. Among patients administered intravenous alteplase, those with a moderate-to-severe decrease in renal function exhibited an elevated risk of sICH (adjusted OR: 10.01; 95% CI: 1.61 to 62.15) and all-cause mortality (adjusted OR: 4.54; 95% CI: 1.48 to 13.91). Comparative treatment effects between tenecteplase and alteplase according to renal function grades showed no heterogeneity.

CONCLUSIONS

A significant correlation was noted between kidney dysfunction and unfavourable outcomes in individuals with AIS who received treatment with either tenecteplase or alteplase.

摘要

目的

关于中风合并肾功能损害并发症患者溶栓治疗的风险效益比，现有证据有限，尤其是对于替奈普酶这种药物。因此，我们研究了肾功能损害与急性缺血性中风（AIS）患者静脉溶栓治疗（IVT）的安全性和有效性之间的关联。

方法

对一项随机对照试验（ClinicalTrials gov. NCT04797013）进行事后分析。在症状发作4.5小时内接受替奈普酶和阿替普酶静脉溶栓治疗（分别为0.25和0.9 mg/kg）的参与者，根据其估计肾小球滤过率分类如下：（1）≥90 mL/min/1.73 m²，肾功能正常；（2）60 - 89 mL/min/1.73 m²，肾功能轻度下降；（3）<60 mL/min/1.73 m²，肾功能中度至重度下降。以肾功能正常分层的患者作为对照。主要疗效和安全结局分别是90天时改良Rankin量表评分为0 - 1的患者百分比和36小时内症状性颅内出血（sICH）的发生率。

结果

在接受静脉替奈普酶治疗的患者中，与肾功能正常相比，肾功能轻度下降（比值比3.10；95%置信区间：1.41至6.78）和肾功能中度至重度下降（比值比：8.03；95%置信区间：2.76至23.38）与全因死亡率较高相关，但与sICH发生率无关。在接受静脉阿替普酶治疗的患者中，肾功能中度至重度下降的患者sICH风险升高（调整后比值比：10.01；95%置信区间：1.61至62.15）和全因死亡率升高（调整后比值比：4.54；95%置信区间：1.48至13.91）。根据肾功能分级，替奈普酶和阿替普酶之间的比较治疗效果无异质性。