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
Creators: name: Schlemm, Ludwig
name: Kufner, Anna
name: Boutitie, Florent
name: Nave, Alexander Heinrich
name: Gerloff, Christian
name: Thomalla, Götz
name: Simonsen, Claus Z.
name: Ford, Ian
name: Lemmens, Robin
name: Muir, Keith W.
name: Nighoghossian, Norbert
name: Pedraza, Salvador
name: Ebinger, Martin
name: Endres, Matthias
Publisher: name: Charité - Universitätsmedizin Berlin
Year: 2019
Subjects: subject: acute therapy
subject: cerebrovascular diseases
subject: ischemic stroke
subject: smoking
subject: thrombolysis (tPA)
subject: treatment outcome and efficacy
subject: 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit

description: 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 &lt; 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 &lt; 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&gt;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): ClinicalTrials.gov, NCT01525290; and EudraCT, 2011-005906-32. Registered 02 February 2012.