Breaking Up is Hard to Do: Are E-Cigarettes the Solution Tobacco Cessation?

Author(s)
Diane Kim, PharmD
Amanda Schartel, PharmD, BCACP

Reviewed By
Maxwell Norris, PharmD
Thaddeus McGiness, PharmD, BCPS
Karen R. Sando, PharmD, BCACP, BC-ADM

Citation
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: 629-37.

The Problem

 

Giving up smoking is the easiest thing in the world. I know because I’ve done it thousands of times. 
       – Mark Twain¹

 

Like Mark Twain, 68% of adult U.S. smokers want to quit, but it often takes many attempts before achieving sustained abstence.² In addition to multiple attempts, most smokers (74.7%) use multiple methods when attempting to quit.  While there are several proven smoking cessation medications available over-the-counter and by prescription, e-cigarettes are being increasingly used for smoking cessation despite the lack of data or official FDA approval for this indication.³  To appropriately advise our patients, it is important to understand the safety and efficacy of e-cigarette use as a potential smoking cessation aid.

 

What’s Known

 

Current recommendations by the U.S. Preventive Services Task Force (USPSTF) promote using a combination of behavioral and pharmacotherapy [nicotine replacement therapy (NRT), bupropion SR, varenicline] interventions to successfully achieve tobacco cessation.  At the time of the publication of the latest recommendations in 2015, there was insufficient evidence for USPSTF to determine the efficacy of e-cigarettes for smoking cessation.⁴ A Cochrane review published in 2014 and updated in 2016 found evidence that e-cigarette use led to increased abstinence rates compared to placebo, but not when compared to the nicotine patch.  These conclusions were based on 24 studies, only three of which were randomized controlled trials.^5,6 Despite the lack of high-quality evidence about their use as a smoking cessation aid, e-cigarette use has become widespread, with sales more than doubling between 2012 and 2016.  The rapid expansion in e-cigarette products available on the market has made it difficult for researchers to keep up with evaluating their efficacy and safety.^7,8

 

What’s New

 

Recently, researchers in the United Kingdom sought to compare the safety and efficacy of e-cigarettes to NRT for smoking cessation in adult smokers.⁹ This was a randomized controlled trial conducted at three sites.  Adult smokers interested in quitting were included if they had no strong preference about the use of e-cigarettes or NRT and were not currently using either product.  Participants were randomized in a 1:1 ratio on their chosen quit dates to receive a refillable e-cigarette starter pack or NRT.  The use of NRT combination regimens (e.g. patch plus gum) was encouraged.  Participants committed to avoiding use of the non-assigned treatment for at least 4 weeks, but were free to switch products thereafter. All participants received the same weekly one-on-one behavioral support.  Carbon monoxide levels were measured at baseline, 4 weeks, and 52 weeks.

 

The primary outcome was 1-year sustained abstinence defined as a self-report of smoking ≤5 cigarettes starting 2 weeks after the quit date (based on the Russell Standard).¹⁰ Sustained abstinence was validated using a carbon monoxide level at 1-year and the result could not be contraindicated by any previous self-report of tobacco use or previous carbon monoxide test.  There were also a number of secondary outcomes (Table 1).

 

 

Table 1: Secondary Outcomes

Sustained abstinence at weeks 4 and 26 and from weeks 26 to 52 Percentage of participants without sustained abstinence from weeks 26 to 52 who reduced their cigarette consumption by at least 50% 7-day abstinence at weeks 4, 26 and 52 Relapse rate and time to relapse

 

 

Table 2: Baseline Characteristics
Characteristic	E-cigarettes (n = 438)	NRT (n = 446)
Median age (IQR) – yr	41 (33 – 53)	41 (33 – 51)
Female sex	48.2%	47.8%
Employed	68.3%	70.9%
Entitled to free prescriptions	41.3%	40.1%
Median no. of cigarettes per day (IQR)	15 (10-20)	15 (10-20)
Fagerström Score  for cigarette dependence (mean ± SD)	4.5 ± 2.5	4.6  ± 2.4
Past use of nicotine replacement	74.9%	74.9%
Past use of e-cigarettes	42.5%	40.6%

IQR = interquartile range

 

Overall, 78.8% of participants completed the 52-week follow-up.  Significantly more patients in the e-cigarette group had sustained abstinence at 1 year compared to the NRT group (18% vs. 9.9%; 95% CI 1.30 to 2.58; P < 0.001; NNT = 12), and abstinence rates were higher in the e-cigarette group at all time points. When patients who used non-assigned products were removed in a post-hoc analysis, the results remained significant (17.7% vs. 8%).  At 52 weeks, 39.5% of participants in the e-cigarette group reported they were still using e-cigarettes compared to 4.3% of the NRT group. The proportion of patients who did not achieve sustained abstinence but who reduced smoking by at least 50% was also significantly more in the e-cigarette group compared to the NRT group (12.8% vs. 7.4%).  Time to relapse and relapse rates at 52 weeks did not differ substantially between the two groups.

 

Of the 49 serious adverse events, none were concluded to be related to the smoking cessation product being used.  Nausea was reported more frequently in the NRT group (37.9% vs. 31.3% in the e-cigarette group) and throat or mouth irritation was more frequent in the e-cigarette group (65.3% vs. 51.2% in the NRT group). By week 4, participants who were abstinent reported little withdrawal discomfort in both groups; those in the e-cigarette group had slightly less urge to smoke, based on the composite urge score which includes a measure of both frequency and strength (2.3 ± 0.9 vs. 2.0 ± 1.0 in the e-cigarette group; mean difference -0.3; 95% CI -0.5 to -0.1).

 

Our Critical Appraisal

 

This is the first large randomized controlled trial that demonstrated greater efficacy of e-cigarettes compared to NRT for smoking cessation.^4,5  The study’s unique design, which allowed participants to have prior exposure to tobacco cessation therapies and to switch between NRT and e-cigarettes after 4 weeks of the assignment, mimics the real-world and makes the results more generalizable.  Additionally, the 12-month follow-up is longer than most smoking cessation studies and better accounts for the dynamic nature of quit attempts and relapses.⁵ Nonetheless, the generalizability of this study is limited by the cultural norms, regulations of, and access to tobacco and e-cigarette products in the UK compared to the United States or other countries.

 

The investigators tried to limit implicit bias in the study by only including participants who had no strong preference for NRT or e-cigarette use.  However, about twice as many patients had prior exposure to NRT compared to e-cigarettes.  An additional limitation to this study is the variable dosing and frequency of use of the two treatments.  It is unclear whether the participants were given recommendations on appropriate dosing or tapering of therapy over time.  While the investigators were able to determine that the nicotine content of e-liquids used by a subgroup of e-cigarette users decreased over time, it is unclear if this finding is true for the majority of e-cigarette patients.  A lack of standardized dosing/tapering of NRT or e-cigarettes may have compromised the results and make it difficult to apply these results to others looking to quit smoking.  Furthermore, during the initial four week treatment period, a far greater proportion of patients in the e-cigarette group reported using their assigned treatment on a daily basis (53% vs. 10.3% for NRT), which reflects the greater satisfaction and perceived helpfulness reported by e-cigarette users.  Thus, the higher abstinence rates in the e-cigarette group may be due to more frequent use of the treatment rather than an inherent difference in treatment efficacy.

 

The Bottom Line

 

We believe these findings, while positive, do not warrant the inclusion of e-cigarettes in the recommended pharmacotherapy options used for tobacco cessation at this time.  One of the goals of smoking cessation is to break the addiction to nicotine and reduce the risk of developing smoking-related diseases. In this study, e-cigarettes did not break the addiction to nicotine. A large proportion of patients were still using e-cigarettes at 52 weeks, suggesting they simply act as a substitute for traditional cigarettes.  While the FDA is now starting to regulate e-cigarettes, little is known about their long-term safety.  This is of particular concern if e-cigarette use is continued for years after someone has “successfully” quit smoking. Furthermore, it is possible that e-liquids may contain substances that pose unique long-term health risks.⁷ As such, we believe any potential benefits are outweighed by these potential safety concerns and the continued dependence on nicotine.  Stricter regulation of e-cigarettes and additional high-quality studies are needed before e-cigarettes can be recommended as a viable quit strategy for smokers.

 

The Key Points

• E-cigarettes have become an increasingly common modality that smokers use to quit smoking despite a lack of long-term safety/efficacy data.
• A recently published study showed that e-cigarette use resulted in significantly higher abstinence rates, greater satisfaction, and less urges to smoke compared to NRT.
• E-cigarettes were still being used by many patients at the end of the study, which indicates that they do not help resolve nicotine addiction. 
• Generally, e-cigarettes should not be recommended for smoking cessation until their benefits/risks have been more clearly established.  However, if patients wish to use e-cigarettes for smoking cessation, they should be counseled on the importance of tapering the dose over time and ultimately discontinuing.

 

FINAL NOTE:  This program will be available for recertification credit through the American Pharmacists Association (APhA) Ambulatory Care Review and Recertification Program.  To learn more, visit https://www.pharmacist.com/ambulatory-care-review-and-recertification-activities.