Findings from the reanalysis of the NINDS tissue plasminogen activator for acute ischemic stroke treatment trial.
OBJECTIVE
Following publication of concerns about the results of the National Institute of Neurological Disorders and Stroke (NINDS) intravenous tissue plasminogen activator (t-PA) in acute stroke treatment trial, NINDS commissioned an independent committee "to address whether there is concern that eligible stroke patients may not benefit from t-PA given according to the protocol used in the trials and, whether the subgroup imbalance (in baseline stroke severity) invalidates the entire trial."


METHODS
The original NINDS trial data were reanalyzed to assess the t-PA treatment effect, the effect of the baseline imbalance in stroke severity between the treatment groups on the t-PA treatment effect, and whether subgroups of patients did not benefit from receiving t-PA.


RESULTS
A clinically important and statistically significant benefit of t-PA therapy was identified despite subgroup imbalances in baseline stroke severity and an increased incidence of symptomatic intracerebral hemorrhage in t-PA treated patients. The adjusted t-PA to placebo odds ratio (OR) of a favorable outcome was 2.1 (95% CI, 1.5 to 2.9). Although these exploratory analyses found no statistical evidence that the t-PA treatment effect differed among patient subgroups, the study was not powered to detect subgroup treatment differences.


CONCLUSIONS
These findings support the use of t-PA to treat patients with acute ischemic stroke within 3 hours of onset under the NINDS t-PA trial protocol. Health professionals should work collaboratively to develop guidelines to ensure appropriate use of t-PA in acute ischemic stroke patients.
Ingall
Timothy John
TJ
Department of Neurology, Mayo Clinic Scottsdale, 13400 East Shea Boulevard, Scottsdale, AZ 85259, USA. ingall.timothy@mayo.edu
O'Fallon
William Michael
WM
Asplund
Kjell
K
Goldfrank
Lewis Robert
LR
Hertzberg
Vicki S
VS
Louis
Thomas Arthur
TA
Christianson
Teresa J Hengy
TJ
D003627:Data Interpretation, Statistical; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012306:Risk; D020521:Stroke / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D016896:Treatment Outcome
D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator