Elsevier

The Lancet

Volume 382, Issue 9905, 16–22 November 2013, Pages 1629-1637
The Lancet

Articles
Electronic cigarettes for smoking cessation: a randomised controlled trial

https://doi.org/10.1016/S0140-6736(13)61842-5Get rights and content

Summary

Background

Electronic cigarettes (e-cigarettes) can deliver nicotine and mitigate tobacco withdrawal and are used by many smokers to assist quit attempts. We investigated whether e-cigarettes are more effective than nicotine patches at helping smokers to quit.

Methods

We did this pragmatic randomised-controlled superiority trial in Auckland, New Zealand, between Sept 6, 2011, and July 5, 2013. Adult (≥18 years) smokers wanting to quit were randomised (with computerised block randomisation, block size nine, stratified by ethnicity [Māori; Pacific; or non-Māori, non-Pacific], sex [men or women], and level of nicotine dependence [>5 or ≤5 Fagerström test for nicotine dependence]) in a 4:4:1 ratio to 16 mg nicotine e-cigarettes, nicotine patches (21 mg patch, one daily), or placebo e-cigarettes (no nicotine), from 1 week before until 12 weeks after quit day, with low intensity behavioural support via voluntary telephone counselling. The primary outcome was biochemically verified continuous abstinence at 6 months (exhaled breath carbon monoxide measurement <10 ppm). Primary analysis was by intention to treat. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12610000866000.

Findings

657 people were randomised (289 to nicotine e-cigarettes, 295 to patches, and 73 to placebo e-cigarettes) and were included in the intention-to-treat analysis. At 6 months, verified abstinence was 7·3% (21 of 289) with nicotine e-cigarettes, 5·8% (17 of 295) with patches, and 4·1% (three of 73) with placebo e-cigarettes (risk difference for nicotine e-cigarette vs patches 1·51 [95% CI −2·49 to 5·51]; for nicotine e-cigarettes vs placebo e-cigarettes 3·16 [95% CI −2·29 to 8·61]). Achievement of abstinence was substantially lower than we anticipated for the power calculation, thus we had insufficient statistical power to conclude superiority of nicotine e-cigarettes to patches or to placebo e-cigarettes. We identified no significant differences in adverse events, with 137 events in the nicotine e-cigarettes group, 119 events in the patches group, and 36 events in the placebo e-cigarettes group. We noted no evidence of an association between adverse events and study product.

Interpretation

E-cigarettes, with or without nicotine, were modestly effective at helping smokers to quit, with similar achievement of abstinence as with nicotine patches, and few adverse events. Uncertainty exists about the place of e-cigarettes in tobacco control, and more research is urgently needed to clearly establish their overall benefits and harms at both individual and population levels.

Funding

Health Research Council of New Zealand.

Introduction

Since their launch in 2004, electronic cigarettes (e-cigarettes), a diverse range of battery operated devices that vaporise nicotine for inhalation, have been purchased by millions of people.1 Many smokers use e-cigarettes to help them quit (27% of those making a quit attempt in the UK, in May, 20132), and sales are increasing so rapidly that some analysts predict that they will surpass cigarette sales within a decade.1

The place of e-cigarettes in tobacco control is controversial,3, 4 and there is a paucity of reliable data to inform debate. Available research suggests that e-cigarettes have the potential to assist smokers to quit or reduce smoking: surveys show that many smokers try e-cigarettes for these reasons,5, 6 and studies show that e-cigarettes are capable of delivering nicotine into the bloodstream and attenuating tobacco withdrawal as effectively as nicotine replacement therapy (NRT).7, 8 Use of e-cigarettes also simulates behavioural and sensory dimensions of smoking. However, a trial in 300 smokers unwilling to quit showed low rates of cessation at 12 months for nicotine e-cigarettes and placebo e-cigarettes.9 E-cigarettes also have potential to harm: researchers have detected toxins in e-cigarette fluid and vapour,10 but at much the same concentrations as with NRT and lower than in cigarette smoke;11 a review deemed e-cigarettes to be very unlikely to pose significant risks to smokers.12

In this trial we aimed to assess whether e-cigarettes with cartridges containing nicotine (nicotine e-cigarette) were more effective for smoking cessation than nicotine patches, and included a blind comparison with e-cigarettes containing no nicotine (placebo e-cigarette). We hypothesised that nicotine e-cigarettes would be more effective than patches and placebo e-cigarettes for smoking reduction, tobacco dependence, and relief of withdrawal symptoms, and that they would have no greater risk of adverse events than nicotine patches.

Section snippets

Study design and participants

We did this three parallel group, randomised controlled trial in Auckland, New Zealand. First randomisation was on Sept 6, 2011, and last follow-up was on July 5, 2013. The published protocol describes procedures in detail.13 In brief, people were eligible if they were aged 18 years or older, had smoked ten or more cigarettes per day for the past year, wanted to stop smoking, and could provide consent. We recruited via community newspapers, inviting people to call the study centre for

Results

Of 1293 people who were assessed, 657 were eligible for inclusion in the study (figure 1). 289 people were assigned to nicotine e-cigarettes, 295 to patches, and 73 to placebo e-cigarettes. Participants' baseline characteristics were evenly balanced between treatment groups (table 1). Overall, loss to follow-up was 22%: 17% (48 of 289) in the nicotine e-cigarettes group, 27% (80 of 295) in the patches group, and 22% (16 of 73) in placebo e-cigarettes group.

Verified continuous abstinence at 6

Discussion

13 weeks of nicotine e-cigarette use resulted in increased smoking abstinence at 6 months compared with use of patches or placebo e-cigarettes, but these differences were not statistically significant. Nevertheless, the results were consistent across a range of analyses, and the 95% CIs do not exclude an advantage. In post-hoc analyses using a 5% non-inferiority limit for the risk difference (on the basis of a margin used in our non-inferiority smoking cessation trial of cytisine26), nicotine

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