E-Cigarettes for Smoking Cessation: The Continued Debate

When electronic cigarettes (e-cigarettes) were introduced to the market, many consumers and experts were hopeful that these products could reduce the harms associated with combustible cigarette smoking and ultimately aid in smoking cessation. Manufacturers promoted these points as benefits associated with e-cigarettes even while the debate continued about their relative harms.

Based on the available evidence, it has become clear that consumer e-cigarette use has led to widespread negative consequences, such as reversing some of the gains in public health efforts against smoking and increasing rates of nicotine consumption as well as eventual cigarette smoking among adolescents.¹

However, some experts note that e-cigarette use may still have a role in smoking cessation when used in a clinical context, and 2 recent studies explored this topic. In a randomized clinical trial (RCT; ClinicalTrials.gov Identifier: NCT02417467) published in November 2020 in JAMA, Mark J. Eisenberg, MD, professor of medicine at McGill University and staff cardiologist and director of the Cardiovascular Health Services Research Group at the Jewish General Hospital at McGill University in Montreal, Quebec, Canada, and colleagues examined the effects of nicotine e-cigarettes combined with individual counseling for smoking cessation.²

Although the trial was initially slated to run for 52 weeks, a prolonged delay in e-cigarette manufacturing necessitated early termination of the trial and reduced enrollment from the original target of 486 participants to 376 participants (mean age, 52 years; 47% women) from 17 sites in Canada. Participants were randomly assigned to receive nicotine e-cigarettes (n=128), nonnicotine e-cigarettes (n=127), or no e-cigarettes (n=121) for a 12-week period, and all received individual counseling.

At 12 weeks, point prevalence abstinence (the primary endpoint) was significantly greater in the nicotine e-cigarette plus counseling group compared to counseling alone (21.9% vs 9.1%; risk difference [RD], 12.8; 95% CI, 4.0-21.6). At 24 weeks, however, the difference between groups was no longer significant (17.2% vs 9.9%; RD, 7.3; 95% CI, -1.2 to 15.7).

While no significant difference was observed between the nonnicotine e-cigarettes plus counseling group and the counseling only group at 12 weeks (17.3% vs 9.1%; RD, 8.2; 95% CI, -0.1 to 16.6), the point prevalence abstinence between groups was significantly greater at 24 weeks (20.5% vs 9.9%; RD, 10.6; 95% CI, 1.8-19.4). The majority of participants in all groups experienced adverse events, most commonly cough and dry mouth.

The authors wrote that interpretation of these results is “limited by early termination and inconsistent findings for nicotine and nonnicotine e-cigarettes, suggesting further research is needed.”²

In a meta-analysis published in February 2021 in the American Journal of Public Health, Richard Wang, assistant professor in the division of pulmonary and critical care medicine at the University of California, San Francisco, School of Medicine, and colleagues explored the link between e-cigarette use and smoking cessation based on 55 observational studies and 9 RCTs.³

In analyses of observational studies, they found that e-cigarette use on a consumer basis was not associated with smoking cessation among adult smokers in general (odds ratio [OR], 0.947; 95% CI, 0.772-1.160) or smokers motivated to quit smoking (OR, 0.851; 95% CI, 0.684-1.057). However, higher rates of cessation were observed in RCTs comparing the effects of e-cigarettes provided to participants for study purposes vs conventional therapy (relative risk, 1.555; 95% CI, 1.173-2.061).

Based on these findings, the authors concluded that e-cigarettes “should not be approved as consumer products but may warrant consideration as a prescription therapy.”³

To glean various perspectives on the potential utility and harm of using e-cigarettes for smoking cessation, we interviewed Dr Eisenberg and Dr Wang, as well as Scott S. Oh, DO, FCCP, associate professor of medicine at the David Geffen School of Medicine at the University of California, Los Angeles, and director of interventional pulmonology at UCLA Health.

What does the evidence suggest thus far regarding whether e-cigarettes are helpful or harmful in smoking cessation?

Dr Eisenberg: Nicotine e-cigarettes appear to be moderately efficacious for smoking cessation and safe when used for a short duration.

Dr Oh: There is limited mixed data on whether e-cigarettes are helpful to those trying to stop smoking. For example, there are studies that show those who use e-cigarettes have less craving for regular cigarettes, less symptoms of nicotine withdrawal, and higher rates of quitting.^4,5

However, other studies have shown that e-cigarette use made no difference. Given the mixed results, it is important not to forget about more established options which have been shown to be helpful in helping people stop smoking, such as group counseling and medications.

Also, it is important to remember we do not yet know the potential long-term effects of e-cigarette use, including the potential for lung damage and cancer. In addition to uncertainty about long-term dangers, there is the possibility of e-cigarette associated acute lung injury or EVALI, which has been associated with nicotine-containing cartridges which were in some cases illicitly obtained.

The potential danger to children should also be considered. E-cigarette cartridges should be kept away from children to prevent accidental nicotine overdose which may be fatal. The danger of second-hand e-cigarette exposure is unknown but is suspected to be less harmful than exposure to traditional second-hand smoke.

What do your recent findings add to our understanding of this topic?

Dr Eisenberg: Among adults motivated to quit smoking, nicotine e-cigarettes compared to counseling alone significantly increased point prevalence abstinence at 12 weeks, but the difference was no longer significant at 24 weeks.²

Reduction in mean self-reported daily cigarette consumption from baseline was significantly greater among participants randomized to nicotine and non-nicotine e-cigarettes compared with counseling alone at 12 weeks and 24 weeks.

Dr Wang: Our work shows that e-cigarettes as consumer products — which is the only way they are available—do not help people quit smoking and may make it harder to quit. Our analysis is based on the largest evidence base to date, and we used observational studies to assess the effect of e-cigarettes on smoking cessation in the real world.³

We also found that the smaller number of randomized controlled trials that assess the value of giving smokers free e-cigarettes as part of a medically supervised smoking cessation program suggests that, in a clinical context, e-cigarettes might be effective. To use e-cigarettes as a medicine, however, they would have to be approved by the US Food and Drug Administration (FDA) as medicines and, as far as we know, no e-cigarette company has applied to have e-cigarettes approved as a medicine.

What are recommendations for clinicians about how to advise patients on this issue in practice?

Dr Eisenberg: When first-line smoking cessation therapies, such as nicotine replacement therapies (eg, patch, gum) and pharmaceutical therapies (eg, varenicline and bupropion) have not worked, nicotine e-cigarettes should be considered as a second- or third-line therapy for smoking cessation.

Though e-cigarettes are generally considered less harmful than conventional cigarettes, patients should use e-cigarettes for the shortest period of time, as their long-term safety is still unknown.

Dr Wang: Clinicians should caution patients who choose to use e-cigarettes or who ask about using e-cigarettes that the risks of e-cigarette use are not fully understood. Clinicians should offer smoking cessation counseling to all patients who smoke and prescribe FDA-approved therapies for those patients who are interested in using them.

Dr Oh: Clinicians cannot make strong recommendations about e-cigarettes given the lack of convincing data for smoking cessation. However, some common sense guidelines have been issued about e-cigarettes:

• E-cigarettes should not be used recreationally, especially in nonsmokers.
• For smokers, e-cigarette use is likely to be less harmful, especially if used short-term to help stop smoking both traditional and e-cigarettes.
• As mentioned, however, it is important to remember that the long-term effects are not yet known.

What should be the focus of future research in this area?

Dr Eisenberg: More research on the safety of long-term e-cigarette use is needed.

In addition, all studies published thus far were done with either first generation (disposable e-cigarettes) or second generation (e-cigarette pens, mods [tank systems], etc) e-cigarettes. With the rapidly evolving e-cigarette market, new smoking cessation studies need to be done using the new pod devices, such as JUUL, to see if these e-cigarettes that are available in higher nicotine content are more effective for smoking cessation.

Dr Wang: More research is needed on the effect of e-cigarettes on the risk of heart disease and lung disease. In particular, research is needed to understand whether concurrent use of cigarettes and e-cigarettes poses a greater risk to health than use of either alone.

Dr Oh: E-cigarettes have the potential to positively impact smoking cessation. However, how to use them optimally to maximize their benefit while minimizing associated risks is not yet clear. Studies to clarify how e-cigarettes fit in with known effective methods as well as long- and short-term dangers will help sort this out.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

References

1. Soneji S, Barrington-Trimis JL, Wills TA, et al. Association between initial use of e-cigarettes and subsequent cigarette smoking among adolescents and young adults:  a systematic review and meta-analysis. JAMA Pediatr. 2017;171(8):788-797. doi:10.1001/jamapediatrics.2017.1488

2. Eisenberg MJ, Hébert-Losier A, Windle SB, et al; for the E3 Investigators. Effect of e-cigarettes plus counseling vs counseling alone on smoking cessation: a randomized clinical trial. JAMA. 2020;324(18):1844-1854. doi:10.1001/jama.2020.18889

3. Wang RJ, Bhadriraju S, Glantz SA. E-cigarette use and adult cigarette smoking cessation: a meta-analysis. Am J Public Health. 2021;111(2):230-246. doi:10.2105/AJPH.2020.305999

4. Adriaens K, Van Gucht D, Declerck P, Baeyens F. Effectiveness of the electronic cigarette: an eight-week Flemish study with six-month follow-up on smoking reduction, craving and experienced benefits and complaints. Int J Environ Res Public Health. 2014;11(11):11220-11248. doi:10.3390/ijerph111111220

5. Perkins KA, Karelitz JL, Michael VC. Effects of nicotine versus placebo e-cigarette use on symptom relief during initial tobacco abstinence. Exp Clin Psychopharmacol. 2017;25(4):249-254. doi:10.1037/pha0000134