Outcomes and Treatment Complications of Intravenous Urokinase Thrombolysis in Acute Ischemic Stroke: A Retrospective Cohort Study

Abstract

Background: Intravenous thrombolysis with alteplase is of proven benefit for eligible patients with acute ischemic stroke. But use of alteplase has serious problems that it is too expensive and the treatment time window of it is too short. Compared to alteplase, urokinase, another drug for intravenous thrombolysis widely used in China, is much cheaper and has a longer treatment time window. This study aimed to assess the outcomes and treatment complications of it in acute ischemic stroke patients, which remains poorly understood before. Methods: This retrospective, multicenter cohort study pooled patients admitted between January 2014 to January 2018 with acute ischemic strokes received intravenous urokinase thrombolysis within six hours from symptom onset from 21 hospitals in China. Outcomes and treatment complications were analyzed by urokinase dose, treatment time window, and stroke severity using univariable and multivariable analyses. Outcomes included were functional independence at 3 months, no/minimal disability, and death with 3 months. Treatment complications analyzed were symptomatic intracranial hemorrhage (ICH), asymptomatic ICH and extracranial bleeding. Findings: A total of 495 patients were identified. Functional independence at 3 months was 60*6%, no/minimal disability was 49*1%, and mortality was 19*6%. 4*2% had symptomatic ICH, 5*5% had asymptomatic ICH, and 10*7% had extracranial bleeding. Patients received high dose urokinase were more likely to have extracranial bleeding (P < 0*001). No statistical differences were found in rates of any outcomes and treatment complications when they are compared among different time window (0-3 h, 3-4*5 h, 4*5-6 h). Stroke severity were associated with functionally independence at 3 months (P < 0*001), death within 3 months (P < 0*001), and symptomatic ICH (P < 0*001). Interpretation: Intravenous urokinase thrombolysis for acute ischemic stroke within six hours from symptom onset is safe. Urokinase may be a good substitute for alteplase for intravenous thrombolysis in acute ischemic stroke. Funding: National Natural Science Foundation of China (81771275) and National Key Clinical Specialties Construction Program of China. Declaration of Interest: The authors declare that they have no conflict of interest. Ethical Approval: The study was approved by the Institutional Review Board of the First Affiliated hospital of Chongqing Medical University, which determined that informed consent was not required for this retrospective study.