Smoking Cessation and Secondary Stroke Prevention

Smoking Cessation and Secondary Stroke Prevention
Dana Osdoba, PharmD, Hennepin County Medical Center 

Background: Many studies have shown that smoking increases risk of stroke, while quitting smoking quickly reduces this risk. However, few studies have shown the effect of quitting smoking after a stroke or transient ischemic attack (TIA) as secondary prevention. The American Heart Association and American Stroke Association guidelines for secondary stroke prevention list smoking cessation as a Class 1 recommendation, however it is only supported by a level of evidence C because of the limited data regarding an association between smoking and recurrent stroke. As research is continuously conducted, more evidence is emerging suggesting that quitting smoking can reduce risk for secondary stroke or TIA.

Evidence: A recent article published in October 2017 by the American Academy of Neurology assessed whether smoking cessation after an ischemic stroke or TIA improves outcomes compared to continued smoking. The study looked at the effect of smoking cessation among participants enrolled in the Insulin Resistance Intervention After Stroke (IRIS) trial. IRIS was a study conducted from 2005 to 2013 involving 3,876 participants from 179 hospitals and clinics in 7 countries. It was a randomized, double-blind, placebo-controlled study. The participants were insulin-resistant, nondiabetic patients with a recent ischemic stroke or TIA. IRIS was designed to test whether pioglitazone, an insulin-sensitizing drug of the thiazolidinedione class, would reduce the incidence of myocardial infarction (MI) and stroke. Patients in the study were followed up for up to 5 years from randomization or to the last scheduled follow-up contact before August 1, 2015, whichever came first. Additionally, IRIS participants were classified according to smoking status at the time of randomization: never smokers, former smokers (stopped smoking before the stroke or TIA event), quitters (quit after the event and not smoking at the time of randomization), or continuing smokers.

The secondary analysis that was completed after the conclusion for the IRIS study was not part of the initial protocol or analysis plan, but was designed after the fact because observational research showed that smoking cessation in patients with established coronary heart disease reduced subsequent all-cause mortality or recurrent cardiovascular events. The primary goal of this secondary analysis was to compare the risk of stroke, MI, or death in patients who quit smoking versus patients who continued to smoke after their index event.

Average follow up occurred at 4.8 years. After this time, stroke, MI, or death had occurred in 60 patients in the quitter group and in 121 in the continuing smoking group, HR 0.66 [95% CI 0.48–0.90]. Death occurred in 23 quitters and 66 continuing smokers, HR 0.49 [95% CI 0.30 – 0.79]. A large difference in death caused by cancer was seen between the quitters group and the continuing smokers. Seven deaths from cancer was seen among the quitters group, compared to 21 among the continuing smokers. This is likely due to the beneficial effects of smoking cessation on reducing cancer risk because at baseline, quitters and continuing smokers had similar cancer and exposure to tobacco histories.

Although this study is very compelling, limitations are present. The analysis of the effects of smoking on TIA/stroke was not included in the initial study design and was not the intent of the IRIS trial. This was a secondary analysis of data from a clinical trial which enrolled insulin-resistant, nondiabetic patients; therefore, the results presented in this analysis may not be applicable to all people who have had a stroke and also smoke.

Discussion: The results of these studies suggest that quitting smoking after an ischemic stroke or TIA would decrease the likelihood of a secondary MI, stroke or death in the following 4.8 years. This study supports the guideline recommendations to quit smoking after stroke or TIA to prevent secondary ischemic events. Although the IRIS trial was not designed to study the impacts of smoking on secondary stroke prevention, the outcomes of the analysis show strong correlation between quitting smoking and reducing outcomes of MI, stroke, and death. More studies designed to study these specific outcomes may be beneficial to further confirm the correlation. 

Clinical Impact: When counseling patients on ways to reduce risk of a secondary stroke after a primary stroke, smoking cessation should always be a part of that conversation. Utilizing motivational interviewing while discussing various nonpharmacological methods and pharmacological options to tobacco cessation with patients may increase the likelihood of quitting. Education about the risks and benefits of quitting may also improve motivation for quitting tobacco use. 

1.       Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45(7):2160–2236.

2.       Epstein KA, Viscoli CM, Spence JD, et al. Smoking cessation and outcome after ischemic stroke or TIA. Neurology. 2017;89(16):1723–1729.

3.       Kaplan RC, Tirschwell DL, Longstreth WT, et al. Vascular events, mortality, and preventive therapy following ischemic stroke in the elderly. Neurology. 2005;65(6):835-842.