Effect of Intravenous Recombinant Tissue-Type Plasminogen Activator in Patients With Mild Stroke in the Third International Stroke Trial-3: Post Hoc Analysis.

Abstract

BACKGROUND AND PURPOSE:

Randomized trial evidence on the risk/benefit ratio of thrombolysis for mild stroke is limited. We sought to determine the efficacy of intravenous recombinant tissue-type plasminogen activator (IV r-tPA) in a subset of patients with mild deficit in the third International Stroke Trial (IST-3).

METHODS:

IST-3 compared IV r-tPA with control within 6 hours of onset in patients for whom IV r-tPA was considered promising but unproven. Analysis was restricted to subjects randomized within 3 hours of onset with a baseline National Institutes of Health Stroke Scale ≤5, pretreatment blood pressure <185/110, and no other r-tPA exclusion criteria. We compared r-tPA and control arms for primary (Oxfordshire Handicap Score [OHS] 0-2) and secondary (ordinal OHS and OHS 0-1) outcomes at 6 months.

RESULTS:

Among 3035 IST-3 subjects, 612 (20.2%) had an National Institutes of Health Stroke Scale ≤5; of these 106 (17.6%) met the restricted criteria. Allocation to r-tPA was associated with an increase in OHS 0 to 2 (84% r-tPA versus 65% control; adjusted odds ratio, 3.31; 95% confidence interval, 1.24-8.79) and a favorable shift in OHS distribution (adjusted odds ratio, 2.38; 95% confidence interval, 1.17-4.85). There was no significant effect of r-tPA on OHS 0 to 1 (60% versus 51%; adjusted odds ratio, 1.92; 95% confidence interval, 0.83-4.43).

CONCLUSIONS:

This post hoc analysis in a highly selected sample of IST-3 supports the rationale of A Study of the Efficacy and Safety of Activase (Alteplase) in Patients With Mild Stroke (PRISMS) trial-a randomized, phase IIIb study to evaluate IV r-tPA in mild ischemic stroke.

• Authors: Pooja Khatri, Darren Tayama, Geoff Cohen, Richard I Lindley, Joanna M Wardlaw, Sharon D Yeatts, Joseph P Broderick, Peter Sandercock, PRISMS and IST-3 Collaborative Groups
• Journal: Stroke (Stroke) Vol. 46 Issue 8 Pg. 2325-7 (Aug 2015) ISSN: 1524-4628 [Electronic] United States
• PMID: 26106113 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 American Heart Association, Inc.

Chemical References

• Fibrinolytic Agents
• Tissue Plasminogen Activator

Topics

• Administration, Intravenous
• Aged
• Aged, 80 and over
• Female
• Fibrinolytic Agents (administration & dosage)
• Humans
• Internationality
• Male
• Stroke (diagnosis, drug therapy, epidemiology)
• Tissue Plasminogen Activator (administration & dosage)
• Treatment Outcome