Generalized efficacy of t-PA for acute stroke : Subgroup analysis of the NINDS t-PA stroke trial

• Published in: Stroke (1970) Vol. 28; no. 11; pp. 2119 - 2125
• Main Author: The NINDS t-PA Stroke Study Group
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.11.1997; American Heart Association, Inc
• Subjects: Acute Disease; Adult; Aged; Biological and medical sciences; Blood. Blood coagulation. Reticuloendothelial system; Cerebrovascular Disorders - drug therapy; Double-Blind Method; Humans; Medical sciences; Middle Aged; National Institutes of Health (U.S.); Pharmacology. Drug treatments; Plasminogen Activators - therapeutic use; Tissue Plasminogen Activator - therapeutic use; United States; United States; Prognosis; Intravenous administration; Indication; Multicenter study; Cardiovascular disease; t-Plasminogen activator; Vascular disease; Randomization; Group selection; Selection criterion; Clinical trial; Cerebrovascular disease; Human; Nervous system diseases; Stroke; Serine endopeptidases; Enzyme; Acute; Cerebral disorder; Peptidases; Chemotherapy; Treatment; Central nervous system disease; Double blind study; Hydrolases; Fibrinolytic
• ISSN: 0039-2499; 1524-4628
• DOI: 10.1161/01.str.28.11.2119

We sought to identify subgroups of stroke patients in whom thrombolytic therapy is particularly hazardous or efficacious. We conducted a post hoc subgroup analysis of a randomized, double-blind, placebo-controlled clinical trial of intravenous tissue plasminogen activator (t-PA) for stroke patients presenting within 3 hours after symptom onset. Before treatment, historical, physical, and laboratory findings were summarized. We identified variables that might predict outcome and/or differential response to t-PA therapy. Outcome was measured with four stroke rating scales administered 3 months after treatment. Statistical significance was assessed with a global outcome procedure that considers the results of all four scales simultaneously. Using regression analysis, we compared the information collected before treatment with the global outcome. Multivariable procedures were used to find information that could guide selection of patients for t-PA therapy. No pretreatment information significantly affected patients response to t-PA. The power of the model to detect a treatment interaction was greater than 90%, and therefore the probability of a type II error is very low. Apart from t-PA therapy, outcome was related to age-by-deficit severity interaction, diabetes, age-by-blood pressure interaction, and early CT findings. These variables and interactions altered long-term patient outcome irrespective of t-PA treatment but did not alter the likelihood of responding favorably to t-PA therapy. Patients should be selected for t-PA thrombolysis according to the guidelines published in the report of the NINDS t-PA Stroke Trial. Further subselection of patients, such as by age or stroke severity, is not supported by our post hoc analysis.