Safety of intravenous recombinant tissue plasminogen activator for treatment of acute ischemic stroke: the Minnesota experience.

Abstract

Background and Purpose Intravenous recombinant tissue plasminogen activator (IV rt-PA) has been shown to reduce the likelihood of disability and death following an acute ischemic stroke by placebo-controlled, randomized clinical trials. We evaluated the safety of this treatment in routine clinical practice by analyzing frequencies and predictors of poor outcomes in patients treated within hospitals in Minnesota. Methods In a retrospective observational cohort study of 576 acute ischemic stroke patients treated with IV rt-PA from January 2008 to June 2010, we reviewed data from 21 hospitals contributing information on stroke admissions to the Minnesota Stroke Registry. We applied multivariate logistic regression to determine association of demographic characteristics, cardiovascular risk factors and stroke severity with symptomatic intracranial hemorrhage, serious systemic hemorrhage and inpatient death. Results Acute ischemic stroke patients administered IV rt-PA were slightly older than non-thrombolytic treatment patients and had significantly higher frequencies of atrial fibrillation, diabetes mellitus and medical history of previous stroke. 4.6% of IV rt-PA patients were diagnosed with symptomatic intracranial hemorrhage (sICH), 1.1% incurred systemic hemorrhage and 7.3% died during their hospitalization. In comparison, 4.7% of patients not treated with any rt-PA died in the hospital. After adjustment for demographic and clinical factors, significant predictors of sICH were National Institutes of Health Stroke Scale (NIHSS) Score OR: 1.14 (1.06 – 1.22), diabetes mellitus OR: 9.97 (1.32 – 75.21), dyslipidemia OR: 6.42 (1.35 – 30.51), hypertension OR: 5.57 (1.11 – 27.98) and medical history of a previous stroke OR: 5.32 (1.03 – 27.62). Higher NIHSS scores were associated with a greater risk of inpatient death. Intravenous thrombolysis 3 – 4.5 hours after stroke symptoms did not increase the risk for sICH or inpatient death when compared with IV rt-PA administration within 3 hours. Patients aged 80 years and older did not incur significantly different inpatient outcomes. Conclusions When compared to the frequencies of poor outcomes reported in clinical trials and previous observational studies, inpatient IV rt-PA clinical outcomes in Minnesota suggest this is a safe treatment. NIHSS Score, diabetes mellitus, dyslipidemia, hypertension and previous stroke are possible risk factors for post-thrombolytic cerebral hemorrhage.