• Nancy A Rigotti, Gina R Kruse, Jonathan Livingstone-Banks, and Jamie Hartmann-Boyce.
• Tobacco Research and Treatment Center, Mongan Institute, Division of General Internal Medicine, Department of Medicine, Massachusetts General Hospital, Boston.
• JAMA. 2022 Feb 8; 327 (6): 566-577.

ImportanceMore deaths in the US are attributed to cigarette smoking each year than to any other preventable cause. Approximately 34 million people and an estimated 14% of adults in the US smoke cigarettes. If they stopped smoking, they could reduce their risk of tobacco-related morbidity and mortality and potentially gain up to 10 years of life.ObservationsTobacco smoking is a chronic disorder maintained by physical nicotine dependence and learned behaviors. Approximately 70% of people who smoke cigarettes want to quit smoking. However, individuals who attempt to quit smoking make an average of approximately 6 quit attempts before achieving long-term abstinence. Both behavioral counseling and pharmacotherapy while using nicotine replacement therapy (NRT) products, varenicline, or bupropion are effective treatments when used individually, but they are most effective when combined. In a meta-analysis including 19 488 people who smoked cigarettes, the combination of medication and behavioral counseling was associated with a quit rate of 15.2% over 6 months compared with a quit rate of 8.6% with brief advice or usual care. The EAGLES trial, a randomized double-blind clinical trial of 8144 people who smoked, directly compared the efficacy and safety of varenicline, bupropion, nicotine patch, and placebo and found a significantly higher 6-month quit rate for varenicline (21.8%) than for bupropion (16.2%) and the nicotine patch (15.7%). Each therapy was more effective than placebo (9.4%). Combining a nicotine patch with other NRT products is more effective than use of a single NRT product. Combining drugs with different mechanisms of action, such as varenicline and NRT, has increased quit rates in some studies compared with use of a single product. Brief or intensive behavioral support can be delivered effectively in person or by telephone, text messages, or the internet. The combination of a clinician's brief advice to quit and assistance to obtain tobacco cessation treatment is effective when routinely administered to tobacco users in virtually all health care settings.Conclusions And RelevanceApproximately 34 million people in the US smoke cigarettes and could potentially gain up to a decade of life expectancy by stopping smoking. First-line therapy should include both pharmacotherapy and behavioral support, with varenicline or combination NRT as preferred initial interventions.

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