Predictors and Consequences of Serious Adverse Events in Patients Treated With Thrombolysis: A Prespecified Secondary Analysis of the AcT Trial

BACKGROUND: With the increasing use of tenecteplase, it is important to understand its safety compared with alteplase. We aimed to determine the incidence, predictors, and functional impact of serious adverse events (SAEs) in patients treated with alteplase versus tenecteplase. METHODS: This is a post hoc analysis of the AcT (Alteplase Compared to Tenecteplase) trial, a phase 3 multicenter randomized controlled trial that randomized 1577 ischemic patients with stroke (2019-2022) into tenecteplase versus alteplase presenting <4.5 hours of onset. SAEs were recorded within 24 hours of treatment and classified by organ system using the Medical Dictionary for Regulatory Activities. Mixed-effects logistic regression evaluated predictors of SAEs and their impact on 90-day modified Rankin Scale. Nervous system disorders were the most common SAE (58.2%), including stroke worsening (26.7%) and intracranial hemorrhage (25%). No significant differences were observed in SAE distribution by thrombolytic. Patients with SAEs had higher 90-day modified Rankin Scale scores (median, 4 versus 2; odds ratio [OR], 3.93 [95% CI, 2.78-5.56]). Independent predictors of SAEs included baseline National Institutes of Health Stroke Scale (per SD increase: OR, 1.2 [95% CI, 1.0-1.5]), large-vessel occlusion (OR, 1.6 [95% CI, 1.1-2.5]), Alberta Stroke Program Early Computed Tomography Score (per point increase: OR, 0.9 [95% CI, 0.8-1.0]), and cerebral atrophy (per point increase: OR, 1.5 [95% CI, 1.1-1.9]). CONCLUSIONS: Our study found no difference between rate or type of SAEs by thrombolytic type, supporting the safety of tenecteplase. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT03889249.