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

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 intra...

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Main Authors: Yongjun Wang, Yilong Wang, Xia Meng, Yuesong Pan, Yu Wu, Yilun Zhou, Wanliang Du, Shuya Li, Mengxing Wang
Format: Article
Language:English
Published: BMJ Publishing Group
Series:Stroke and Vascular Neurology
Online Access:https://svn.bmj.com/content/early/2025/03/18/svn-2024-003726.full
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author Yongjun Wang
Yilong Wang
Xia Meng
Yuesong Pan
Yu Wu
Yilun Zhou
Wanliang Du
Shuya Li
Mengxing Wang
author_facet Yongjun Wang
Yilong Wang
Xia Meng
Yuesong Pan
Yu Wu
Yilun Zhou
Wanliang Du
Shuya Li
Mengxing Wang
author_sort Yongjun Wang
collection DOAJ
description 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 m2,normal renal function; (2) 60–89 mL/min/1.73 m2, mildly decreased renal function; and (3) <60 mL/min/1.73 m2, 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.
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series Stroke and Vascular Neurology
spelling doaj-art-279d760dd9d146deacf55831932295a62025-08-20T02:40:42ZengBMJ Publishing GroupStroke and Vascular Neurology2059-869610.1136/svn-2024-003726Influence 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 trialYongjun Wang0Yilong Wang1Xia Meng2Yuesong Pan3Yu Wu4Yilun Zhou5Wanliang Du6Shuya Li7Mengxing Wang81 Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China2 China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China4 China National Clinical Research Center for Neurological Diseases, Beijing, ChinaChina National Clinical Research Center for Neurological Diseases, Beijing, China2Providence Therapeutics Holdings, Inc., Calgary, AB, CanadaDepartment of Nephrology, Capital Medical University, Beijing 100050, ChinaChina National Clinical Research Center for Neurological Diseases, Beijing, ChinaChina National Clinical Research Center for Neurological Diseases, Beijing, ChinaChina National Clinical Research Centre for Neurological Diseases, Beijing, ChinaObjective 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 m2,normal renal function; (2) 60–89 mL/min/1.73 m2, mildly decreased renal function; and (3) <60 mL/min/1.73 m2, 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.https://svn.bmj.com/content/early/2025/03/18/svn-2024-003726.full
spellingShingle Yongjun Wang
Yilong Wang
Xia Meng
Yuesong Pan
Yu Wu
Yilun Zhou
Wanliang Du
Shuya Li
Mengxing Wang
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
Stroke and Vascular Neurology
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
url https://svn.bmj.com/content/early/2025/03/18/svn-2024-003726.full
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