Smoking influences outcome in patients who had thrombolysed ischaemic stroke: the ENCHANTED study

Lingli Sun, Lili Song, Jie Yang, Richard I Lindley, Thompson Robinson, Pablo M Lavados, Candice Delcourt, Hisatomi Arima, Bruce Ovbiagele, John Chalmers, Craig S Anderson, Xia Wang, Lingli Sun, Lili Song, Jie Yang, Richard I Lindley, Thompson Robinson, Pablo M Lavados, Candice Delcourt, Hisatomi Arima, Bruce Ovbiagele, John Chalmers, Craig S Anderson, Xia Wang

Abstract

Background and purpose: As studies vary in defining the prognostic significance of smoking in acute ischaemic stroke (AIS), we aimed to determine the relation of smoking and key outcomes in patient participants who had thrombolysed AIS of the international quasi-factorial randomised Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED).

Methods: Post-hoc analyses of ENCHANTED, an international quasi-factorial randomised evaluation of intravenous alteplase-dose comparison and levels of blood pressure control in patients who had thrombolysed AIS. Multivariable logistic regression models with inverse probability of treatment weighting (IPTW) propensity scores were used to determine associations of self-reported smoking status and clinical outcomes, according to 90-day modified Rankin Scale (mRS) scores and symptomatic intracerebral haemorrhage (sICH).

Results: Of 4540 patients who had an AIS, there were 1008 (22.2%) current smokers who were younger and predominantly male, with more comorbidities of hypertension, coronary artery disease, atrial fibrillation and diabetes mellitus, and greater baseline neurological impairment, compared with non-smokers. In univariate analysis, current smokers had a higher likelihood of a favourable shift in mRS scores (OR 0.88, 95% CI 0.77 to 0.99; p=0.038) but this association reversed in a fully adjusted model with IPTW (adjusted OR 1.15, 95% CI 1.04 to 1.28; p=0.009). A similar trend was also apparent for dichotomised poor outcome (mRS scores 2-6: OR 1.18, 95% CI 1.05 to 1.33; p=0.007), but not with the risk of sICH across standard criteria.

Conclusion: Smoking predicts poor functional recovery in patients who had thrombolysed AIS.

Trial registration number: NCT01422616.

Keywords: stroke; thrombolysis.

Conflict of interest statement

Competing interests: RTL reports personal fees from Covidien and Pfizer; HA reports lecture fees from Takeda, Daiichi Sankyo, Astellas, and Aska Pharmaceuticals; outside the submitted work; JC reports research grants and lecture fees from Servier for the ADVANCE trial and post-trial follow-up; BO reports receiving fees for service on the data and safety monitoring committee of the THALES (ticagrelor) trial. CA reports personal lecture fees and travel support, and grants paid to his institution, from Takeda China.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Forest plot for symptomatic intracerebral haemorrhage (ICH) variables at 90 days. ECASS2/3, second and third European Cooperative Acute Stroke Studies; IST3, third International Stroke Trial; NINDS, National Institute of Neurological Disorders and Stroke; SITS-MOST, Safe Implementation of Thrombolysis in Stroke-Monitoring Study.

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