Type of study: Randomized, multicenter, controlled trial

The Finding: This study is a two-group, pragmatic, multicenter, individually randomized, controlled trial. National Health Service (NHS) stop-smoking services are available free across the United Kingdom. This trial was conducted in three service sites from May 2015 through February 2018. A total of 886 participants underwent randomization to e-cigarette or nicotine-replacement. Treatment included weekly behavioral support for at least 4 weeks. The primary outcome was sustained abstinence for 1 year, which was validated biochemically at the final visit. Of the randomly assigned participants, 78.8% completed the 52-week follow-up. The rate of sustained 1-year abstinence was 18.0% in the e-cigarette group and 9.9% in the nicotine-replacement group (relative risk, 1.83; 95% confidence interval [CI], 1.30 to 2.58; P<0.001). The absolute difference in the 1-year abstinence rate between the two groups was 8.1 percentage points, resulting in a number needed to treat for one additional person to have sustained abstinence of 12 (95% CI, 8 to 27). E-cigarettes were more effective for smoking cessation than nicotine-replacement therapy, when both products were accompanied by behavioral support.

Strength and weaknesses:
Strengths: Randomized, multicenter, controlled trial
Weaknesses: The trial had several limitations. Product assignments could not be blinded. Positive expectations have limited effects on long-term abstinence, but if nicotine replacement was seen as an inferior option, participants in the nicotine-replacement group could have put less effort into their quit attempt than those in the e-cigarette group. We tried to limit expectation effects by recruiting only participants with no strong product preference. Abstinence rates in the nicotine-replacement group were also at least as high as in usual practice²⁴(see the Supplementary Appendix). Nevertheless, lack of blinding could affect the results. Carbon monoxide validation detects smoking only over the past 24 hours, so there may have been some false negative results. Several participants in the nicotine-replacement group used e-cigarettes during the trial, but this would dilute rather than amplify any effects of e-cigarettes. The 1-year follow-up rate of 79% was similar to the rates of 78%,¹⁹79%,⁵and 75%²⁰observed in other studies involving the same general population and setting. Achieving higher follow-up rates among smokers engaged in face-to-face treatment is difficult, because they tend to feel embarrassed if they do not quit, and some avoid further contact. Multiple imputation showed consistent results; nevertheless, incomplete follow-up represents another limitation of the trial.

Relevance: switching completely from cigarette smoking to e-cigarette use would be expected to reduce risks to health. There are questions about risks and benefits of use of e-cigarettes for different purposes, but an important clinical issue is whether e-cigarette use in a quit attempt facilitates success, particularly as compared with the use of nicotine-replacement therapy. A Cochrane review showed that e-cigarettes with nicotine were more effective for smoking cessation than nicotine-free e-cigarettes.⁴A trial that compared e-cigarettes with nicotine patches for smoking cessation used cartridge e-cigarettes with low nicotine delivery and no face-to-face contact. It showed similar low efficacy for both treatments. This trial evaluated the 1-year efficacy of refillable e-cigarettes as compared with nicotine replacement when provided to adults seeking help to quit smoking and combined with face-to-face behavioral support. E-cigarettes were more effective for smoking cessation than nicotine-replacement therapy in this randomized trial.