Abstract T MP21: Effect of IV rtPA in Mild Strokes in the Third International Stroke Trial (IST3): A Post Hoc Analysis
BACKGROUND: A relatively small number of patients with mild ischemic stroke (NIHSS 0-5) had been included in randomized trials of IV tPA up to 2012, and debate continues about the balance of risk and benefit from thrombolysis in this group. In the recent IST3 trial, among patients with NIHSS 0-5, 221/304 (72.7%) tPA vs. 232/308 (75.3%) control subjects were alive and independent (OHS 0-2) at 6 months, a nonsignificantly adverse effect. To determine whether a further trial in mild stroke patients was justified, we examined the effect of tPA in a more restricted subset of IST3 patients with NIHSS 0-5 who met NINDS tPA Study criteria.
METHODS: The IST3 trial was a pragmatic, international, randomized-controlled, open-treatment trial with broad entry criteria comparing IV tPA with control within 6 hours of onset in 3035 subjects conducted in 12 countries outside the USA. We restricted analysis to subjects with NIHSS 0-5 who were treated within three hours, had pretreatment BP<185/110, and met all other NINDS tPA Study criteria. No age restriction was applied. The primary outcome was the proportion alive and independent (OHS 0-2) at 6 months; key secondary analyses were an ordinal analysis of OHS and the proportion alive and with ‘favorable outcome’ (OHS 0-1). (Details at www.ist3.com).
RESULTS: 612 of 3035 (20.2%) subjects enrolled in the IST3 trial had an NIHSS of 0-5. 106 of 612 (17.6%) were recruited within 3 hours, had pretreatment BP<185/110, and met all NINDS tPA Study criteria. In this subset, tPA was associated with a significant increase in the proportion alive and independent, and a favorable shift in distribution of OHS grades. There was no significant effect on ‘favorable outcome’. See Table.
CONCLUSIONS: This post-hoc analysis in a highly selected sample of the IST3 trial supports the rationale of the PRISMS trial, a randomised placebo-controlled Phase III, 950-subject, 75-center, North American study to evaluate the efficacy and safety of IV tPA in mild ischemic strokes.
Author Disclosures: P. Khatri: Honoraria; Modest; Academic Grand Rounds (paid to Dept). Other; Modest; Taylor and Francis-Stroke Ctr Handbook book royalties (paid to Dept). Research Grant; Significant; NIH/NINDS (IMS III, NSTN NCC/RCC). Other Research Support; Significant; Significant; Genentech-PRISMS Trial PI (paid to Dept), Penumbra-THERAPY Trial PI (paid to Dept). D. Tayama: Employment; Significant; Genentech. Ownership Interest; Significant; Roche. G. Cohen: None. R.I. Lindley: None. J.M. Wardlaw: None. S.D. Yeatts: Other Research Support; Significant; Genentech (PRISMS Trial SC). J.P. Broderick: Other Research Support; Modest; Novo Nordisk. Consultant/Advisory Board; Modest; Pfizer, Inc. P. Sandercock: Other Research Support; Modest; Drug and placebo for 300 patients donated to IST-3 by Boehringer Ingelheim. Honoraria; Modest; Honoraria (paid to the Department) and travel expenses from Boehringer Ingelheim for occasional lectures given at international conferences. Consultant/Advisory Board; Modest; He was a member of the Independent Data and Safety Monitoring Board (DSMB) of the RELY trial funded by Boehringer Ingelheim and received attendance fees and travel expenses for attending DSMB meetings.
- © 2014 by American Heart Association, Inc.