AUTHOR=Schlemm Ludwig , Kufner Anna , Boutitie Florent , Nave Alexander Heinrich , Gerloff Christian , Thomalla Götz , Simonsen Claus Z. , Ford Ian , Lemmens Robin , Muir Keith W. , Nighoghossian Norbert , Pedraza Salvador , Ebinger Martin , Endres Matthias 

TITLE=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

JOURNAL=Frontiers in Neurology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2019.01239

DOI=10.3389/fneur.2019.01239

ISSN=1664-2295

ABSTRACT=<p><bold>Background:</bold> 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.</p><p><bold>Methods:</bold> We performed a pre-specified <italic>post-hoc</italic> 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.</p><p><bold>Results:</bold> 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; <italic>p</italic> &lt; 0.001) and less often had arterial hypertension (45.0% vs. 56.8%; <italic>p</italic> = 0.02) or atrial fibrillation (3.8% vs. 15.3%; <italic>p</italic> &lt; 0.001). The acute stroke presentation was more often due to large vessel occlusion among current smokers (27.1 vs. 16.2%; <italic>p</italic> = 0.01), and smokers had a trend towards more severe strokes (National Institutes of Health Stroke Scale score&gt;10 in 27.1% vs. 19.5%; <italic>p</italic> = 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 (<italic>p</italic>-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], <italic>p</italic> = 0.04).</p><p><bold>Conclusions:</bold> 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.</p><p><bold>Clinical Trial registration:</bold> Main trial (WAKE-UP): <ext-link ext-link-type="uri" xlink:href="https://ClinicalTrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">ClinicalTrials.gov</ext-link>, NCT01525290; and EudraCT, 2011-005906-32. Registered 02 February 2012.</p>