Current smoking does not modify the treatment effect of intravenous thrombolysis in acute ischemic stroke patients—a post-hoc analysis of the WAKE-UP trial

Schlemm, L. et al. (2019) Current smoking does not modify the treatment effect of intravenous thrombolysis in acute ischemic stroke patients—a post-hoc analysis of the WAKE-UP trial. Frontiers in Neurology, 10, 1239. (doi: 10.3389/fneur.2019.01239) (PMID:31824412) (PMCID:PMC6883001)

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Background: The “smoking paradox” indicates that patients with acute ischemic stroke (AIS) who smoke at the time of their stroke may have a better prognosis after intravenous thrombolysis than non-smokers. However, findings are inconsistent and data analyzing the effect of smoking on treatment efficacy of intravenous thrombolysis are scarce. Methods: We performed a pre-specified post-hoc subgroup analysis of the Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke (WAKE-UP) trial that randomized AIS patients with unknown time of symptom onset who had diffusion-weighted imaging-fluid attenuation inversion recovery (DWI-FLAIR) mismatch to either alteplase or placebo. Patients were categorized as current smokers or non-smokers (including former smokers and never-smokers). Baseline demographic and clinical characteristics, as well as clinical and imaging follow-up data were analyzed according to smoking status. Results: Four hundred and eighty six patients were included in the analysis. Current smokers (133, 27.4%) were younger (60.1 ± 13.0 vs. 67.2 ± 10.3 years; p < 0.001) and less often had arterial hypertension (45.0% vs. 56.8%; p = 0.02) or atrial fibrillation (3.8% vs. 15.3%; p < 0.001). The acute stroke presentation was more often due to large vessel occlusion among current smokers (27.1 vs. 16.2%; p = 0.01), and smokers had a trend towards more severe strokes (National Institutes of Health Stroke Scale score>10 in 27.1% vs. 19.5%; p = 0.08). The treatment effect of alteplase, quantified as odds ratio for a favorable outcome (modified Rankin Scale [mRS] score at 90 days of 0 or 1), did not differ between current smokers and non-smokers (p-value for interaction: 0.59). After adjustment for age and stroke severity, neither the proportion of patients with favorable outcome, nor the median mRS score at 90 days differed between current smokers and non-smokers. When additional potential confounders were included in the model, the median mRS score was higher in current smokers than in non-smokers (cOR of better outcome for current smokers vs. non-smokers: 0.664 [0.451–0.978], p = 0.04). Conclusions: In patients with mild to moderate MRI-proven AIS and unknown time of symptom onset with DWI-FLAIR mismatch, current smokers had worse functional outcome as compared to non-smokers. Current smoking did not modify the treatment effect of alteplase. Clinical Trial registration: Main trial (WAKE-UP):, NCT01525290; and EudraCT, 2011-005906-32. Registered 02 February 2012.

Item Type:Articles
Additional Information:The main clinical trial, WAKE-UP, was funded by a grant from the European Union Seventh Framework Program (278276). LS and AN are participants in the BIH-Charité Clinical Scientist Program funded by the Charité–Universitätsmedizin Berlin and the Berlin Institute of Health. We acknowledge support from the German Research Foundation (DFG) and the Open Access Publication Fund of Charité–Universitätsmedizin Berlin.
Glasgow Author(s) Enlighten ID:Muir, Professor Keith and Ford, Professor Ian
Authors: Schlemm, L., Kufner, A., Boutitie, F., Nave, A. H., Gerloff, C., Thomalla, G., Simonsen, C. Z., Ford, I., Lemmens, R., Muir, K. W., Nighoghossian, N., Pedraza, S., Ebinger, M., and Endres, M.
Subjects:R Medicine > R Medicine (General)
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 (Online):1664-2295
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Frontiers in Neurology 10:1239
Publisher Policy:Reproduced under a Creative Commons License

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