Abstract 188: Safety and Efficacy of off-label Intravenous Thrombolysis in Patients With Acute Ischemic Stroke: An Observational Study From the International Safe Implementation of Treatments in Stroke (SITS) Registry

Abstract

Introduction: Intravenous thrombolysis is the only approved pharmacological treatment for acute ischemic stroke. Due to strict license regulations, off-label treatment is common. We aimed to analyze the safety and efficacy of off-label thrombolysis. Methods: Retrospective analysis of 56258 patients from the Safe Implementation of Treatments in Stroke (SITS) thrombolysis registry was performed regarding 11 off-label criteria according to the European license for alteplase. Symptomatic intracranial hemorrhage (SICH) according to SITS was defined as primary safety endpoint and SICH according to the European Cooperative Acute Stroke Study II (ECASS II) definition and the National Institute of Neurological Disorders and Stroke (NINDS) definition as secondary safety endpoints. Favorable outcome, defined as modified Rankin Scale score 3 months after stroke between 0 and 2 was the primary efficacy endpoint. Multivariable logistic regression analyses after replacing missing values using multiple imputations were performed for the efficacy and safety endpoints. Results: In total, 16740 (30%) patients received off-label thrombolysis. SICH according to the SITS definition occurred in 1037 (1.8%) patients. The only two off-label criteria constituting independent positive and negative predictors for SICH according to the SITS definition were elevated blood pressure (OR 1.39; p=0.012) and minor stroke (OR 0.51; p=0.002). Very severe stroke, history of stroke and diabetes, age and high glucose levels were additional independent predictors of SICH according to the ECASS II and NINDS definition. Favorable outcome was found in 24834 patients (54.5%). Independent predictors of favorable outcome comprised of minor stroke (positive predictor) and very severe stroke, history of stroke and diabetes, age and elevated blood pressure (all negative predictors). Inclusion of SICH according to the ECASS II definition in the multivariable analysis did not change the OR of these off-label criteria. Conclusions: Thrombolysis appears to be safe and efficient for most of the off-label criteria. Individual risk-benefit evaluation should be performed before off-label thrombolysis, especially in patients with combinations of these off-label criteria.