Post-hoc analysis of outcome of intravenous thrombolysis in infarcts of infratentorial localization in the WAKE-UP trial

Galinovic, I. et al. (2019) Post-hoc analysis of outcome of intravenous thrombolysis in infarcts of infratentorial localization in the WAKE-UP trial. Frontiers in Neurology, 10, 983. (doi: 10.3389/fneur.2019.00983) (PMID:31572293) (PMCID:PMC6749039)

Abstract

Introduction: In WAKE-UP (Efficacy and Safety of MRI-based Thrombolysis in Wake-Up Stroke), patients with an acute stroke of unknown onset time were randomized to treatment with intravenous alteplase or placebo, guided by MRI. Methods: In this exploratory post-hoc secondary analysis we compared clinical and imaging data, as well as treatment effects and safety of intravenous thrombolysis between patients with infra- vs supratentorial stroke. Results: Forty-eight out of 503 randomized patients (9.5%) presented with a stroke involving the cerebellum or brainstem. Patients with infratentorial stroke were younger compared to patients with supratentorial stroke (mean age 60 vs 66 years), more frequently male (85% vs 62%), and less severely affected (median NIHSS 4.5 vs 6.0). There was no heterogeneity for treatment effect between supratentorial (OR 1.67 95% CI 1.11 – 2.51) and infratentorial (OR 1.31 95% CI 0.41 – 4.22) sub-groups (test for interaction p=0.70). In patients with infratentorial stroke, favorable outcome (a score of 0-1 on the modified Rankin scale (mRS) at 90 days) was observed in 12/22 patients (54.5%) in the alteplase group and in 13/25 patients (52.0%) in the placebo group (p=0.59). The primary safety endpoint (death or mRS 4-6 at day 90) occurred in 3 patients of the alteplase group (13.6%) and 3 patients in the placebo group (12.0%); p=0.74. Discussion: WAKE-UP was underpowered for demonstrating treatment effect in subgroup analyses however, based on our current results, there is no evidence to recommend withholding MRI-guided thrombolysis in patients with unknown onset stroke of infratentorial localization.

• Item Type: Articles
• Additional Information: We acknowledge support from the German Research Foundation (DFG) and the Open Access Publication Fund of Charité– Universitätsmedizin Berlin. WAKE-UP received funding from the European Union Seventh Framework Program [FP7/2007– 2013] under grant agreement no. 278276 (WAKE-UP).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Muir, Professor Keith and Ford, Professor Ian
• Authors: Galinovic, I., Boutitie, F., Fiebach, J., Villringer, K., Cheng, B., Ebinger, M., Endres, M., Fiehler, J., Ford, I., Thijs, V., Lemmens, R., Muir, K., Nighoghossian, N., Pedraza, S., Simonsen, C. Z., Roy, P., Gerloff, C., and Thomalla, G.
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre; College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Journal Name: Frontiers in Neurology
• Publisher: Frontiers Media
• ISSN: 1664-2295
• ISSN (Online): 1664-2295
• Copyright Holders: Copyright © 2019 The Authors
• First Published: First published in Frontiers in Neurology 10:983
• Publisher Policy: Reproduced under a Creative Commons License