Recombinant tissue plasminogen activator for minor strokes: The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Experience

Study objective: Acute ischemic stroke patients eligible for tissue plasminogen activator and with less severe neurologic deficits, although still generally benefiting from therapy, may have a different risk-benefit profile than all eligible acute stroke patients. We address whether patients with a minor stroke should receive tissue plasminogen activator, analyze minor stroke syndromes in the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Study, and define what constitutes a "minor stroke." Methods: The NINDS rt-PA Stroke Study included 624 patients with acute ischemic stroke within 180 minutes of symptom onset within a randomized, double-blind, placebo-controlled trial. To explore the relationship among stroke severity, thrombolytic therapy, and stroke outcome, we defined minor strokes (5 specified definitions) based on the standardized data available at treatment decision, including National Institutes of Health Stroke Scale score. We studied prespecified clinical outcomes, including 3-month favorable outcome (global statistic) defined from a set of standardized clinical scales, dichotomized clinical outcome at 3 months (good=modified Rankin Scale <= 2, bad=modified Rankin Scale > 2), and risk of symptomatic intracerebral hemorrhage. Results: For each of the 5 definitions of minor stroke, adjusted odds ratios for treatment benefit were consistently 2.0 with the lower 95% confidence limit, ranging from 1.4 to 1.5, and the upper 95% confidence limit, ranging from 2.7 to 2.9. There were less frequent "bad" outcomes (modified Rankin Scale > 2) after therapy with tissue plasminogen activator than placebo. Symptomatic intracerebral hemorrhage within 36 hours of treatment had a frequency in the tissue plasminogen activator-treated subjects, ranging from 0% to 4%, depending on minor stroke definition. Conclusion: Recognizing the limitations of post hoc subgroup analyses, we could not detect a difference in the beneficial effects of tissue plasminogen activator in patients with minor stroke syndromes compared to the overall treatment effects in the entire cohort. Our data suggest that the risk-benefit ratio for using tissue plasminogen activator in minor-stroke patients favors treatment in eligible patients.