TY - JOUR
T1 - Findings from the reanalysis of the NINDS tissue plasminogen activator for acute ischemic stroke treatment trial
AU - Ingall, Timothy John
AU - O'Fallon, William Michael
AU - Asplund, Kjell
AU - Goldfrank, Lewis Robert
AU - Hertzberg, Vicki S.
AU - Louis, Thomas Arthur
AU - Hengy Christianson, Teresa J.
PY - 2004/10
Y1 - 2004/10
N2 - Background and Purpose - 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.
AB - Background and Purpose - 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.
KW - Randomized controlled trials
KW - Stroke, acute
KW - Tissue plasminogen activator
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U2 - 10.1161/01.STR.0000140891.70547.56
DO - 10.1161/01.STR.0000140891.70547.56
M3 - Article
C2 - 15345796
AN - SCOPUS:4944222683
SN - 0039-2499
VL - 35
SP - 2418
EP - 2424
JO - Stroke
JF - Stroke
IS - 10
ER -