Searching for the Smoker’s Paradox in Acute Stroke Patients Treated With Intravenous Thrombolysis

Inconsistent evidence supports better outcome in smokers after stroke. Our study examines this association in a large sample of ischemic stroke treated with intravenous thrombolysis. Virtual International Stroke Trials Archive (VISTA) database, composed of individual patient data of multiple clinical trials, was queried. The primary outcome was functional independence at 3 months noted by modified Rankin Scale (mRS; a 7-point scale ranging from 0 [no deficit] to 6 [death]) score≤ 2. The secondary outcomes were National Institutes of Health Stroke Scale (NIHSS; stroke severity measure, ranging from 0 [no deficit] to 42 [most severe]) score at 24 hours and the occurrence of symptomatic intractracranial hemorrhage. A total of 5383 patients were included: 1501 current smokers and 3882 nonsmokers. Smokers were younger (60 ± 13 vs. 71 ± 12 years, p < .0001) and had lower median NIHSS score at baseline (12 [8-17] vs. 13 [9-18], p < .0001). The rate of favorable functional outcome (mRS ≤ 2) at 3 months was significantly higher among current smokers (49.7% vs. 39.5%, p < .0001) and with crude ORs of 1.52, 95% CI 1.33-1.72. The association became non-significant after adjusting for age (OR 1.11, 95% CI 0.97-1.27). Subgroup analysis by age/gender strata showed that current smoking was associated with favorable outcome only in women ≥ 65 years. Current smoking was also associated with lower rates of symptomatic intracranial hemorrhage (adjusted OR 0.55, 95% CI 0.39-0.79). Smokers experience their first ever stroke 11 years younger than nonsmokers. This age difference explains the association between current smoking and favorable functional outcome. Smoking is associated with occurrence of first ever stroke at a younger age, therefore, focus should be on smoking prevention and treatment. The decision to treat ischemic stroke patients with intravenous thrombolysis should not be influenced by the patients' smoking status.