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.

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 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.