Tissue plasminogen activator for acute ischemic stroke in clinical practice - A meta-analysis of safety data

Background and Purpose - Concerns persist regarding the safety of tissue plasminogen activator ( tPA) therapy for acute ischemic stroke. Numerous case series of clinical experience with tPA have been published that provide additional data on the safety of thrombolytic therapy. Methods - This is a meta- analysis of 15 published, open- label studies that broadly followed approved indications and guidelines for tPA use in nonselective patient populations. Results - In 2639 treated patients, the symptomatic intracerebral hemorrhage rate was 5.2% ( 95% confidence interval, 4.3 to 6.0), slightly lower than the 6.4% rate in the treated group of the randomized, placebo- controlled National Institute of Neurological Disorders and Stroke ( NINDS) trial. The mean total death rate ( 13.4%) and proportion of subjects achieving a very favorable outcome ( 37.1%) were comparable to the NINDS trial results. Protocol deviations were reported in 19.8%. Comparing across studies showed that the mortality rate was correlated with the percentage of protocol violations ( r = 0.67, P = 0.018). Conclusions - Postapproval data support the safety of intravenous thrombolytic therapy with tPA for acute ischemic stroke, especially when established treatment guidelines are followed.