Smoking Cessation

Risk Factors:

United States. Surgeon General's Advisory Committee on Smoking and Health, and United States. Public Health Service. Office of the Surgeon General. Smoking and Health. United States. Public Health Service. Office of the Surgeon General, 1964. Official Report This landmark U.S. Surgeon General’s report added to the growing international recognition of the multiple hazards of cigarette smoking:


Leone FT, Zhang Y, Evers-Casey S, et al. Initiating pharmacologic treatment in tobacco-dependent adults. An official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2020; 202:e5-e31. This guideline is most noteworthy for recommending preferential use of varenicline, including in patients with a comorbid psychiatric condition and in patients who are not ready to quit smoking, over other pharmacologic treatments and e-cigs. Combination therapy and duration of therapy are also addressed.
PMID: 32663106
Free Full Text

Electronic Cigarettes and Smoking Cessation:

Prochaska JJ. The public health consequences of e-cigarettes: a review by the National Academies of Sciences. A call for more research, a need for regulatory action. Addiction. 2019; 114:587-89. This FDA-sponsored review summarizes the findings of more than 800 research studies on the safety of electronic nicotine delivery systems (published before widespread recognition of EVALI). The paper calls attention to the uncertain balance between harm reduction (e-cigarettes less toxic than continued tobacco smoking) and the risk of exposure in younger generations.
PMID 30347473
Free Full Text

Farber HJ, Gallego MCP, Galiatsatos P, et al. Harms of electronic cigarettes: what the healthcare provider needs to know.  Ann Am Thorac Soc. 2021; 18:567-572. Review summarizes risks of e-cigarette use as well as efficacy of e-cigs for smoking cessation.
PMID: 33284731

Halpern SD, Harhay MO, Saulsgiver K et al.  A pragmatic trial of e-cigarettes, incentives, and drugs for smoking cessation. N Engl J Med. 2018; 378:2302-2310. This study is noteworthy for finding low levels of abstinence at 6 months regardless of the strategy employed. Over 6,000 smokers were randomized to usual care or usual care plus one of the following groups: 1) free cessation aids (nicotine-replacement therapy or pharmacotherapy, with e-cigarettes if standard therapies failed); 2) free e-cigarettes, without a requirement that standard therapies had been tried; 3) free cessation aids plus $600 in rewards for sustained abstinence; or 4) free cessation aids plus $600 deposited as redeemable funds with money removed if cessation milestones were not met. Sustained 6-month abstinence was uniformly low - usual care with 0.1%, group 1 with 0.5%, group 2 with 1.0%, group 3 with 2%, and group 4 with 2.9%. There was no statistical difference between receiving e-cigarettes and usual care or free cessation aids.
PMID: 29791259
Free Full Text

Hajek P, Phillips-Waller A, Przulj D, et al. A randomized trial of e-cigarettes versus nicotine-replacement therapy. N Engl J Med. 2019; 380:629-637. In contrast to the Halpern study above, this RCT was noteworthy for finding higher rates of abstinence, particularly in those assigned to e-cigarettes. Of the 886 participants, abstinence rates were 18% among those randomized to e-cigarette group vs 9.9% in NRT group. Of note, among participants who were abstinent at one year, those in the e-cigarette group were more likely than NRT group to be using their assigned product (80% vs 9%).
PMID: 30699054
Free Full Text

Pharmacologic Interventions:

Single drug:

Transdermal Nicotine Study Group. Transdermal nicotine for smoking cessation. Six-month results from two multicenter controlled clinical trials. JAMA 1991; 266:3133-8. This landmark study was the first to assess rates of continuous smoking abstinence among patients who had successfully quit after a 6-week trial of transdermal nicotine replacement.
PMID: 1956099

Combination therapy:

Walker N, Parag V, Verbiest M, et al. Nicotine patches used in combination with e-cigarettes (with and without nicotine) for smoking cessation: a pragmatic, randomised trial. Lancet Respir Med. 2020; 8:54-64.  This trial examined nicotine replacement alone vs in combination with nicotine or nonnicotine e-cigarettes. Six-month abstinence was achieved in 7% of those on NRT/nicotine e-cig, 4% NRT/nonnicotine e-cig, and 2% on sole NRT. There was a greater loss to follow up in the NRT only group which could have impacted the results.
PMID: 31515173

Baker TB, Piper ME, Smith SS, et al. Effects of combined varenicline with nicotine patch and of extended treatment duration on smoking cessation: a randomized clinical trial. JAMA. 2021; 326;1485-93. This trial found no difference in abstinence at 52 weeks with either adding nicotine replacement to varenicline or in extending duration of therapy from 12 to 24 weeks. Smoking cessation, based on carbon monoxide-confirmed self-reported 7-day point prevalence abstinence, was near 24% in all groups, higher than many other cessation trials.
PMID: 34665204

Long-term effects of smoking cessation interventions:

Anthonisen NR, Skeans MA, Wise RA, et al. The effects of a smoking cessation intervention on 14.5 year mortality. Ann Intern Med 2005; 142:233-9. This article is noteworthy for showing smoking cessation reduces mortality even when the intervention is successful in only a minority of patients. The study compared a 10-week intervention that combined counseling and nicotine gum with usual care among smokers with obstructive lung disease. Quit rates at 5 years were 21.7% and 5.4% in the intervention and usual care groups, respectively. At 14.5 years, the hazard ratio for all-cause mortality in the usual care group vs. the intervention group was 1.18 (95% CI 1.02 to 1.37).
PMID: 15710956
Free Full Text