Clinical question: Do pharmacotherapies used in tobacco cessation treatment significantly increase the risk of cardiovascular events?
Background: Although it is known that smoking cessation is the most beneficial enhancement of cardiovascular health, many clinicians may be hesitant to prescribe pharmacotherapies because of concerns regarding adverse events. This study reports the cardiovascular safety findings from EAGLES (Evaluating Adverse Events in a Global Smoking Cessation Study) and its nontreatment extension trial.
Study design: Double-blind, randomized, triple-dummy, placebo- and active-controlled trial and its nontreatment extension trial.
Setting: Conducted by 140 multinational centers, EAGLES was a trial in cohorts of smokers with and without psychiatric disease that assessed the safety and efficacy of pharmacotherapies used for smoking cessation.
The EAGLES extension trial is a nontreatment extension of EAGLES. It began with the first dose of medication and included those who completed an additional 28 weeks of observation.
Synopsis: The study included approximately 8,000 participants aged 18-75 years who smoked 10 or more cigarettes per day and were interested in quitting. The study monitored the development of a major adverse cardiovascular event (MACE), such as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, during treatment with varenicline, bupropion hydrochloride, nicotine replacement therapy, and placebo therapy. Other end points included determining the occurrence of MACE along with other peripheral vascular disease that required either intervention, coronary revascularization, or hospitalization for unstable angina (MACE+).
There were no significant differences in time to MACE or MACE+ overall across all observation periods.
Possible limitations of the study were its exclusion criteria and baseline characteristics of participants. The study excluded participants with unstable psychiatric illness, active substance abuse, clinically significant cardiovascular disease in the 2 months prior to the study entry (MI or coronary artery bypass graft), clinically significant cerebrovascular disease in the 2 months prior to study entry (stroke or documented transient ischemic attack), or inadequate control of hypertension as judged by investigators at screening and baseline. Of the included participants, greater than 66% of the participants were in the low risk (less than 10%) cardiovascular risk category, less than 10% had diabetes, less than 5% had coronary heart disease, and less than 1% had carotid artery disease.
Bottom line: The findings provide evidence that, in a general population of smokers, smoking cessation medications do not increase the risk of serious cardiovascular events.
Citation: Benowitz N et al. Cardiovascular safety of varenicline, bupropion, and nicotine patch in smoker..
Dr. White is a hospitalist in the division of hospital medicine in the department of medicine at Loyola University Chicago, Maywood, Ill.