Tissue plasminogen activator for acute ischemic stroke in clinical practice: a meta-analysis of safety data.
OBJECTIVE
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.
Graham
Glenn D
GD
Albuquerque VA and University of New Mexico School of Medicine, Department of Neurology, VA Medical Center, Albuquerque, NM 87122, USA. graham@unm.edu
D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D002543:Cerebral Hemorrhage / Q000401:mortality; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D019983:Guideline Adherence / Q000706:statistics & numerical data; D006801:Humans; D011446:Prospective Studies; D012189:Retrospective Studies; D012449:Safety / Q000706:statistics & numerical data*; D020521:Stroke / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D010959:Tissue Plasminogen Activator / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator