Efficacy and safety of urokinase intravenous thrombolysis in minor stroke according to large vessel occlusion status: a subgroup analysis of the TRUST trial

Abstract

The risk-benefit profile of thrombolytic therapy in minor stroke patients with large vessel occlusion (LVO) remains uncertain. This post hoc analysis of the TRUST trial (ThRombolysis with Urokinase for minor Stroke Trial) sought to comparatively assess whether the presence of large vessel occlusion (LVO) modifies the efficacy and safety of urokinase intravenous thrombolysis, compared with best medical treatment(BMT), in patients with minor stroke. This post-hoc exploratory analysis included patients from the TRUST trial with available vascular imaging data, categorized in the LVO and the non-LVO group. Each group was further divided into the UK thrombolysis group and the BMT group. Primary efficacy outcome was the proportion of patients achieving a modified Rankin Scale (mRS) score of 0–1 at 90 days. Safety outcomes included symptomatic intracranial hemorrhage (sICH) within 36 h and all-cause mortality within 90 days. Of the 999 patients enrolled in the TRUST trial, 605 were included in the current study. UK thrombolysis was not associated with a 90-day excellent functional outcome in minor stroke patients, either in LVO patients (adjusted risk ratio [RR] 1.90, 95% CI 0.63–2.26) or in non-LVO patients (adjusted RR 1.02, 95% CI 0.84–1.23) compared with the BMT group (p for interaction = 0.41). In the LVO group, UK thrombolysis showed a non-significant trend toward reduced mortality (adjusted RR 0.04, 95% CI 0.01–1.65), whereas no such effect was observed in non-LVO patients (adjusted RR 0.52, 95% CI 0.11–2.52). No significant interaction was found between groups (p for interaction = 0.25). In addition, there were no patients who experienced sICH in subgroup analysis. This subgroup analysis found no improvement in 90-day functional outcomes with UK thrombolysis in minor stroke patients, irrespective of LVO presence, while maintaining a comparable safety profile with regard to mortality and sICH. The TRUST trial was registered with ClinicalTrials. gov (NCT 04420351). Registration Date: June 04, 2020.