Abstract
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): ClinicalTrials.gov, NCT01525290; and EudraCT, 2011-005906-32. Registered 02 February 2012.
Highlights
Intravenous thrombolysis with recombinant tissue plasminogen activator is an effective treatment option for eligible patients with acute ischemic stroke (AIS) that improves functional outcome [1, 2] and reduces long-term disability [3]
There is conflicting evidence in the literature as to whether current smoking is associated with a better prognosis in patients with AIS treated with alteplase [4,5,6,7,8,9]
We examined whether smoking status at the time of stroke occurrence modified the treatment effect of alteplase in terms of functional recovery in patients with AIS enrolled in the Efficacy and Safety of magnetic resonance imaging (MRI)-Based Thrombolysis in Wake-Up Stroke (WAKE-UP) trial [13]
Summary
Intravenous thrombolysis with recombinant tissue plasminogen activator (alteplase) is an effective treatment option for eligible patients with acute ischemic stroke (AIS) that improves functional outcome [1, 2] and reduces long-term disability [3]. There are no data that describe the potential effect of current smoking as a treatment effect modifier of intravenous thrombolysis with alteplase in patients with MRI-proven AIS. It has been hypothesized that current smoking may modify the treatment effect of alteplase by lowering levels of endogenous tissue plasminogen activator. This would induce a hypercoagulable state which in turn favors the formation of fibrin-rich thrombi that are more susceptible to fibrinolytic treatment [12]. Findings are inconsistent and data analyzing the effect of smoking on treatment efficacy of intravenous thrombolysis are scarce
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