Quitkey - The Evidence Linking Smoking Cessation to Reduced Stroke Risk

The Evidence Linking Smoking Cessation to Reduced Stroke Risk

Talan, Jamie

Neurology Today: October 5, 2017 - Volume 17 - Issue 19 - p 1,33–39

doi: 10.1097/01.NT.0000526505.98791.04



In a study showing the impact of smoking on ischemic stroke, researchers reported that the five-year risk for stroke was 22 percent in patients who continued to smoke compared with 15.7 percent in people who quit, a 34 percent relative risk reduction. The study was one of the first to focus rigorously on the association between smoking cessation and secondary stroke.

Cigarette smoking cessation has been reported to be key to reducing the risk of vascular disease and death after ischemic stroke, but until now, scientists have not examined the association with rigorous methods.

Now, a research team from Yale University School of Medicine was able to analyze data from 3,876 non-diabetic patients enrolled in the Insulin Resistance Intervention after Stroke (IRIS) study to do just that.

“We were quite surprised how little research had been done in this area,” said senior investigator Walter N. Kernan, MD, professor of medicine at Yale School of Medicine. “The IRIS protocol included high-quality baseline data on smoking and complete follow-up data on vascular outcomes and death. We were able to use this data to estimate the health benefits of smoking cessation in the high-risk population of patients with symptomatic cerebrovascular disease.”

The investigators, led by first author Katherine Epstein, a fourth-year medical student, compared rates of the composite outcome of stroke, myocardial infarction (MI), or death over five years among patients with a recent ischemic stroke or transient ischemic attack (TIA) who continued to smoke and patients who quit.

The scientists reported that the five-year risk for stroke was 22 percent in patients who continued to smoke compared with 15.7 percent in people who quit, a 34 percent relative risk reduction. The results were published in the September 8 online edition of Neurology.

“We expected that smoking cessation would have a positive impact,” said Epstein. “But no one had ever shown it outside of a small observational study. We hope that many doctors use this finding to help counsel their patients to stop smoking.”

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The IRIS study recruited 3,876 non-diabetic men and women with a recent stroke or TIA (within six months) into a study to test whether pioglitazone could reduce the risk of a subsequent stroke or MI over a five-year study period. The study began in 2005 and the last patient follow-ups were in 2015. The patients were recruited from 179 hospitals and clinics in seven countries.

The investigators obtained information on several lifestyle measures, including smoking, at the start of the study and continued to ask questions about these behaviors at each annual exam. The IRIS investigators also obtained detailed lifetime smoking histories and contacted patients four times a year to receive information about medical events, including stroke, heart attack, and cancer diagnoses.

About 1,072 (or 28 percent) of the patients were smoking at the time of their initial stroke or TIA. At baseline, 1,490 were classified as former smokers, 450 as quitters after their cerebrovascular event, and 622 continued to smoke. The average duration of smoking was 40 years.

After a median follow-up of 4.8 years, 60 patients in the group that quit smoking had a stroke, MI or had died, compared to 121 patients who had continued to smoke. Twenty-three quitters and 66 patients still smoking had died (6.1 percent versus 13.1 percent). Mortality among all causes was significantly higher in the smokers compared to quitters. Cancer was the main cause of death.

The Yale scientists calculated the risk: Seven deaths among quitters were attributable to cancer compared to 21 among those who continued smoking (1.5 percent vs 3.4 percent; p=0.07). A lower percentage of deaths from cerebrovascular disease (0.2 percent vs 1.6 percent, p=0.03); heart disease (0.7 percent vs 1.6 percent; p=0.16); and unknown causes (1.8 percent vs 2.9 percent; p=0.24) was also observed among those who had quit smoking.

The researchers also reported that 145 of the 450 quitters said that they resumed smoking during one or more annual interviews and that 190 of 622 continuing smokers reported that they had quit at some point during the five-year follow-up.

Dr. Kernan said that the relative-risk reduction (34 percent) and the absolute risk reduction (6.9 percent) are comparable or better than those associated with many other medical treatments for secondary stroke prevention. That includes antiplatelet therapy, statin therapy, lowering blood pressure, and pioglitazone. (Anticoagulation for atrial fibrillation has higher reductions in relative and absolute risk, he said.)

Dr. Kernan said neurologists can offer this message to their patients: “Among 100 patients who continue to smoke after an ischemic stroke or TIA, you could expect that 23 of them will have a stroke, MI or death within five years compared to 16 out of 100 patients who quit. Seven fewer will have one of these serious events. And the benefits begin to emerge in the first year.”

“Helping patients quit smoking after a stroke or TIA should be a high priority,” he added. “These results can help in counselling patients to stop smoking. That is the message. If you quit smoking you can decrease your risk, and the longer you stay clear of smoking, the more benefits you will have.”

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“As much as we can do with individual medical interventions for stroke risk factors, there is a huge need for public health interventions to reduce the risk for stroke,” said Amelia Boehme, PhD, an assistant professor of epidemiology in the department of neurology at the College of Physicians and Surgeons at Columbia University, who wrote an accompanying editorial in Neurology.

“Primary preventions have shown a benefit with smoking cessation,” she said in an interview with Neurology Today. “This study shows an effect for secondary stroke prevention, as well. It's wonderful to quantify it, and highlight that interventions for smoking reduction remain a public health concern. More research and intervention strategies are needed to help people quit,” she added, noting that many people in the study resumed smoking after they had quit.

“This is an unplanned, post-hoc analysis of clinical trial data,” said Larry Goldstein, MD, FAAN, professor and chairman of neurology and co-director of the Kentucky Neuroscience Institute at the University of Kentucky. “In such analyses there is always a risk of unmeasured confounding. Nonetheless, it is an important finding that further supports guideline recommendations for smoking cessation. It wouldn't be ethical to do a randomized prospective trial of smoking cessation.”

He also pointed out that the benefit was for a reduction in the combined outcome of stroke, MI or death, which were most commonly related to cancer. “The study did not have sufficient power to assess the impact of cessation on recurrent stroke or any of the component endpoints alone. Lifestyle changes to reduce cardiovascular risk are an important component of an overall preventive strategy.”

“We know a lot about primary prevention strategies for stroke,” said Philip B. Gorelick, MD MPH, executive medical director of the Mercy Health Hauenstein Neurosciences and professor of translational science and molecular medicine at Michigan State University College of Human Medicine. “But this is an important reminder that smoking is a key risk factor for recurrent stroke and cancer death and it's well worth our efforts to encourage patients to quit smoking.”

“Many people believe that smoking should be a fifth vital sign,” he added. “Often, smoking cessation gets lost in the shuffle.” His team also works on helping patients meet the American Heart Association and American Stroke Association guidelines for recurrent stroke prevention.

“This is one of the best secondary prevention studies that has been done,” said John Cole, MD, associate professor of neurology at the Baltimore VA Medical Center and the University of Maryland School of Medicine. He finds that the time of the initial event is the best time to talk about smoking cessation.

“Patients are vulnerable and they are more likely to listen to the facts. This study says it all: Stop smoking and you can reduce your risk for another event. Don't sugarcoat things. Smoking is a major risk factor. Make this your opportunity to educate the smoker and his or her family on the risks. Recommend strategies and treatments. Put smoking cessation in the discharge summary so that the patient's primary care doctor can follow through.”



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