The rise of electronic cigarettes (“e-cigs,” “electronic nicotine delivery systems,” or “ENDS”) has provoked vigorous debate within the public health community and among health care providers. Some view these products with, at best, skepticism of any potential benefits to tobacco cigarette smokers and at worst as a serious threat of undermining the significant reduction in tobacco smoking rates over the past 50 years and providing a gateway to use of combustible tobacco. Others view e-cigarettes as a disruptive technology that has the potential to make tobacco smoking obsolete, add to the therapeutic options for treatment of tobacco dependence, and provide public health benefits for years to come.
These divergent views were reflected in open letters sent to the World Health Organization last year, with one group of public health experts emphasizing the potential benefits and harm reduction of e-cigarettes and the other emphasizing the risks to youth and urging more caution. Although the debate continues, there is limited scientific evidence to support proponents on either side. One major challenge to researchers is the rapidly changing technology in e-cigarettes that frequently outpaces efforts to study them.
Nevertheless, the popularity of e-cigarettes continues to rise, particularly among youth. The most recent Centers for Disease Control and Prevention report showed e-cigarette use among middle and high school students increasing, with use tripling between 2013 and 2014 (1.1% to 3.9% for middle school students, and 4.5% to 13.4% for high school students).1 Over this same time period, tobacco cigarette use dropped from 15.8% to 9.2%. This may argue against a gateway effect (i.e., moving from e-cigarettes to smoked tobacco), at least at the current time. Whether these trends will continue remains to be seen.
As use and knowledge of these products increases among adults, questions posed to health care providers regarding the utility of e-cigarettes for smoking cessation will likely become increasingly common. With respect to e-cigarette efficacy in promoting smoking cessation, data are beginning to trickle in, but the evidence remains unclear. Multiple survey studies have suggested that at least some smokers have had success in quitting or reducing smoking and attenuating craving and withdrawal symptoms.2,3 The most recent Cochrane meta-analysis evaluating e-cigarette data for smoking cessation was notable for how few studies it contained.4 Their review identified just 13 completed studies; two were randomized controlled trials and 11 were cohort studies. The authors rated the overall quality of evidence as “low” or “very low” and suggested that further research will greatly influence effect estimates.
Randomized Controlled Trials
The ASCEND trial
The ASCEND trial was conducted in New Zealand and randomly selected 657 tobacco smokers who wanted to quit smoking to one of three conditions for 12 weeks: nicotine e-cigarette (16 mg/ml cartridge), non-nicotine e-cigarette, or nicotine patch.5 Carbon monoxide–validated quit rates at 6 month follow-up were unexpectedly low in all groups and not statistically different (7.3%, 5.8%, and 4.1% in the nicotine e-cigarette, nicotine patch, and placebo e-cigarette groups, respectively). There was a noteworthy difference in the proportion of smokers who reduced cigarette consumption by 50% or more between the e-cigarette and patch users (57% vs. 41%, relative risk [RR] 1.41, 95% CI [1.20, 1.67]).
The ECLAT trial
The ECLAT trial was conducted in Italy and randomly selected 300 tobacco smokers who did not intend to quit smoking to one of three conditions: fixed-dose nicotine e-cigarette (7.2 mg/ml) for 12 weeks, variable-dose nicotine e-cigarette (7.2 mg/ml for 6 weeks, then 5.2 mg/ml for 6 weeks), or non-nicotine e-cigarette for 12 weeks.6 One-year abstinence rates were higher in the two nicotine e-cigarette groups (13% and 9%) compared with the placebo e-cigarette group (4%), but this difference was not significant. Nicotine e-cigarette users showed a trend that was not statistically significant (25.5% vs. 16%, RR 1.30, 95% CI [0.70, 2.44]) toward reducing smoking consumption by 50% or more compared to the placebo group of e-cigarette users.
In combining the data from the two studies, nicotine e-cigarette use was associated with higher abstinence rates than placebo e-cigarette use (RR 2.29, 95% CI [1.0, 4.96]) and increased likelihood of reducing cigarette consumption by at least 50% (RR 1.31, 95% CI [1.02, 1.68]), but these effects were relatively small.4 Importantly, these trials had several limitations. First, they were single-center studies and used early-generation e-cigarette products that are likely now considered obsolete. Nicotine delivery from the e-cigarette was likely low, if present at all, and guidance for use of the products was limited. Second, low levels of behavioral and pharmacologic support were provided, and the ECLAT study involved only individuals who were not motivated to quit. Third, because of unexpectedly low overall quit rates in the ASCEND trial, the sample size may have been underpowered to detect differences between groups.
Advising Patients on E-Cigarette Use
ASCO and the American Association for Cancer Research recently issued a joint statement on electronic nicotine delivery systems.2,3 The statement concluded that there are currently insufficient safety and efficacy data to recommend e-cigarettes for use by the general population or for patients with cancer for smoking cessation. Other key recommendations in the statement included: (1) additional research on e-cigarettes, including assessment of health impact, understanding patterns of use, and determining what role e-cigarettes have in tobacco smoking cessation; (2) product regulation at the federal, state, and local level to ensure appropriate reporting of product ingredients, childproof caps on liquids, and warning labels on products and their advertisements; (3) prohibition of child-friendly flavors; and (4) prohibiting e-cigarette use in places where tobacco smoking is prohibited.
Given the limited evidence available, what should we tell our patients who want to use e-cigarettes as a means to quit smoking tobacco? First and foremost, we should praise the patient for expressing interest in quitting smoking, and we must not discourage a quit attempt, regardless of whether we agree with the patient’s approach.
Second, we should educate patients about the U.S. Food and Drug Administration–approved therapies for tobacco dependence that are proven to be effective, and we should strongly recommend these treatments as first-line: nicotine replacement therapy (patch, gum, lozenge, inhaler, and nasal spray), varenicline, bupropion, and various combinations of these medications. We should inquire about prior experiences patients have had with these approved therapies, and we should try to identify and remove previous barriers to treatment. With adequate dosing and the combination of multiple medications, patients who had previous unsuccessful attempts to quit using approved therapies may, in fact, respond to approved therapy and achieve abstinence. Behavioral counseling should also be added to the patient’s treatment plan whenever possible, as the combination of behavioral and pharmacotherapy is superior to either modality alone.
Third, we must identify patients who have truly not had success with approved therapies during multiple quit attempts, who are adamantly unwilling to use them, or who insist on e-cigarette use. We must educate these patients about the currently limited state of knowledge about e-cigarettes, while still emphasizing that quitting tobacco smoking is the highest priority. We should inform these patients that e-cigarettes are not harmless and are not currently regulated by the U.S. Food and Drug Administration. We must also emphasize that e-cigarettes have not been around long enough to know the long-term effects, nor has there been sufficient evidence to establish their efficacy in promoting smoking cessation. With those caveats, it is reasonable to support a patient’s attempt to quit tobacco smoking using e-cigarettes in specific circumstances. For instance, patients may come to you having initially quit smoking tobacco by using e-cigarettes. In such a case, it is important to praise the patient, and to advise them on weaning off of the e-cigarette, which they can begin doing by gradually lowering the e-cigarette’s nicotine content. Although the ultimate goal is making our patients completely smoke and vape free, we must always emphasize that abstinence from tobacco smoking is the highest priority.
About the Authors: Dr. Baldassarri is a research and clinical fellow in Pulmonary and Critical Care Medicine at Yale School of Medicine. Dr. Herbst is Ensign Professor of Medicine (Medical Oncology) and Professor of Pharmacology and chief of medical oncology at Yale Cancer Center and Smilow Cancer Hospital at Yale-New Haven. He is also the associate director for translational research and translational working group leader, Thoracic Oncology Program, at Yale Cancer Center. Dr. Toll is associate professor of Public Health Services and chief of Tobacco Cessation and Health Behaviors of the Hollings Cancer Center at the Medical University of South Carolina and lecturer in psychiatry at the Yale School of Medicine.