Smoking cessation: benefits versus risks of using pharmacotherapy to quit.

S moking cessation benefits health and lengthens life expectancy at any age. With that rationale, smoking cessation figures centrally in comprehensive tobacco control initiatives, including the recommendations of the US Preventive Services Task Force and the World Health Organization. 3,4 The population of the United States has recognized the personal benefits of stopping smoking and, at present, the majority of those who have ever smoked cigarettes have stopped. Public health benefits have been realized. Smoking cessation is a powerful driver of the decline in cardiovascular mortality over the past 4 decades and also of the more recent declines in rates of smoking-caused cancers among men. The decline in smoking over the past 4 decades reflects the combined effects of multiple factors, including the widespread recognition of the adverse health consequences of smoking, clean indoor air laws and regulations, the general denormal-ization of tobacco smoking, rising prices, and the promotion of cessation. The promotion of cessation has been accomplished through education, engagement of the healthcare community , quit lines, and the use of various therapies, including pharmacotherapy, to increase the success of quit attempts. Nicotine-replacement therapy (NRT), launched as nicotine gum in 1984, was the first pharmacological therapy for cessation to be approved by the Food and Drug Administration. Subsequently, other forms of NRT were licensed including the patch, lozenges, inhaler, and nasal spray. NRT was switched to over-the-counter access in 1996. Following NRT, bupropion, an antidepressant, was shown to be an effective smoking cessation therapy and released as Zyban (GlaxoSmithKline) in 1997. The most recently licensed pharmacological agent for smoking cessation is varenicline, licensed as Chantix (Pfizer) in the United States in 2006. The mechanisms of action for these 3 medications differ: NRT by directly replacing the nicotine in tobacco products, bupropion by mitigating the symptoms of withdrawal, and varenicline by acting as a partial nicotine agonist. Each of these medications, used in conjunction with appropriate counseling and support, increases the likelihood of sustained cessation; in a 2013 meta-analysis, bupropion and NRT approximately doubled quit rates, whereas varenicline had a significantly higher success rate, almost 3-fold that of placebo. 8 Each of these agents has also been linked to diverse adverse effects, including recent and controversial concerns for cardiovascular disease (CVD) risk. In this issue of Circulation, Mills and colleagues 11 report the findings of a network meta-analysis on risks for cardio-vascular events associated with these 3 medications. Their analytic …