From the Editor
Last week, I spoke to a patient who wanted passes off the ward so that he could smoke. When I suggested that we could help him reduce his nicotine use – and maybe even help him quit – he responded: “I’ve been smoking for 40 years. I’ll never quit.”
As much as the comment is disappointing, it is all too familiar. Nicotine is highly addictive, and it’s very challenging for our patients to quit.
What then to make of e-cigarettes? While they have been marketed well for smoking cessation, the evidence to date has been lacking. Do they offer a pathway to ending nicotine use? Or are e-cigarettes another type of nicotine product – addictive and ultimately unhelpful?
This week, we look at a paper just published in The New England Journal of Medicine. Queen Mary University of London’s Peter Hajek and his co-authors report on a “pragmatic, multicenter, individually randomized, controlled trial” comparing e-cigarettes to nicotine replacement therapy (NRT). It’s the first adequately powered study on this topic. And this Very Big Paper comes with a Very Big Result: e-cigarettes offered a strong advantage over NRTs.
Great ad, great product?
In this week’s Reading, we look at the Hayek et al. paper and consider e-cigarettes.
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E-Cigs and Cessation
“A Randomized Trial of E-Cigarettes versus Nicotine-Replacement Therapy”
Peter Hajek, Anna Phillips-Waller, Dunja Przulj, Francesca Pesola, Katie Myers Smith, Natalie Bisal et al.
The New England Journal of Medicine, 30 January 2019
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. A 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… Our 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.
So begins a new paper by Hajek et al. considering e-cigarettes.
Here’s what they did:
- The authors “conducted a two-group, pragmatic, multicenter, individually randomized, controlled trial.”
- The trial had three service sites in the UK, and ran from May 2015 to February 2018.
- Participants were recruited through participating services and through social media.
- Exclusion criteria included pregnancy and breast feeding.
- Participants were randomized into two groups. Nicotine-Replacement Group: participants were able to select among various products (including patch, gum, and mouth strip); combinations were allowed. “Participants were also free to switch products.” E-Cigarette Group: participants were offered a second-generation e-cigarette (a One Kit starter pack with 30-mL bottle of flavoured e-liquid, and an additional 10 mL available upon request). Participants in both groups received weekly behavioural support for at least 4 weeks.
- Data was collected for several measures including: smoking status, withdrawal symptoms, respiratory symptoms.
- There were follow ups, including at 52 weeks.
- Statistical analyses were done.
Here’s what they found:
- 886 participants underwent randomization – 439 formed the e-cigarette group and 447 formed the nicotine-replacement group.
- “Of the randomly assigned participants, 78.8% completed the 52-week follow-up.”
- “The sample was composed largely of middle-aged smokers…”
- “The rate of sustained 1-year abstinence was 18.0% in the e-cigarette group and 9.9% in the nicotine-replacement group… 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…” !!
- “Overall adherence was similar in the two groups, but e-cigarettes were used more frequently and for longer than nicotine replacement.”
- Though there were several adverse events (27 in the e-cigarette group and 22 in the nicotine-replacement group), none were associated with the products.
- “[N]ausea was reported more frequently in the nicotine-replacement group (37.9%, vs. 31.3% in the e-cigarette group) and throat or mouth irritation more frequently in the e-cigarette group (65.3%, vs. 51.2% in the nicotine-replacement group). There was little difference between the two groups in the percentage of participants reporting severe nausea (6.6% in the e-cigarette group and 6.5% in the nicotine-replacement group) or severe throat or mouth irritation (5.9% and 3.9%, respectively)
- “[T]he incidence of cough and phlegm production declined in both trial groups from baseline to 52 weeks. However, among participants who reported cough or phlegm at baseline, significantly more were symptom-free at the 52-week follow-up in the e-cigarette group than in the nicotine-replacement group…”
E-cigarettes were more effective for smoking cessation than nicotine-replacement therapy in this randomized trial. This is particularly noteworthy given that nicotine replacement was used under expert guidance, with access to the full range of nicotine-replacement products and with 88.1% of participants using combination treatments.
A few thoughts:
- The Hayek et al. paper is interesting.
- The authors found a clear result. (!)
- There is much to like here: the study was multicentre, randomized trial of e-cigarettes. It was also pragmatic. CMAJ Deputy Editor Matthew Stanbrook notes on Twitter that “the first adequately powered RCT with the primary objective of comparing e-cigarettes with NRT. This is evidence that clinicians worldwide have badly needed in a controversial context.” He also notes that there are no competing interests declared by the authors.
- Of course, no study is perfect. On Twitter, Dr. Stanbrook notes several problems. Start here: the study was unblinded. You can find his thread of tweets here: https://twitter.com/drstanbrook/status/1091014695866298370.
- While e-cigarettes were superior to NRT, cigarettes are tough to quit: the vast majority of people in both groups remained smokers at 52 weeks. Ouch.
- The paper runs with two editorials. I highlight: “E-Cigarettes to Assist with Smoking Cessation” by Belinda Borrelli and George T. O’Connor, both of Boston University. They summarize the Hajek et al. paper, but note their hesitation with e-cigarettes: “A key finding of Hajek et al. is that among participants with sustained abstinence at 1 year, 63 of 79 (80%) in the e-cigarette group were still using e-cigarettes, whereas only 4 of 44 (9%) in the nicotine-replacement group were still using nicotine replacement. This differential pattern of long-term use raises concerns about the health consequences of long-term e-cigarette use. E-cigarette vapor contains many toxins and exerts potentially adverse biologic effects on human cells in vitro or in animal models, although toxin levels and biologic effects are generally lower than those of tobacco smoke. A study involving humans showed an altered bronchial epithelial proteome in association with e-cigarette use, including some protein alterations also seen among tobacco smokers.In a mouse model, inhalational exposure to nebulized e-cigarette liquid containing nicotine resulted in distal airspace enlargement that was consistent with pulmonary emphysema. These findings argue against complacency in accepting the transition from tobacco smoking to indefinite e-cigarette use as a completely successful smoking-cessation outcome.” What then are the clinical implications for the Hajek et al. paper?
We recommend that e-cigarettes be used only when FDA-approved treatments (combined with behavioral counseling) fail, that patients be advised to use the lowest dose needed to manage their cravings, and that there be a clear timeline and ‘off ramp’ for use. Use of e-cigarettes should be monitored by health care providers, like other pharmacologic smoking-cessation treatments.
This conclusion strikes me as quite reasonable for us clinicians.
The full editorial can be read here: https://www.nejm.org/doi/full/10.1056/NEJMe1816406.
- There remains a larger public-policy concern with e-cigarettes. Maybe they are more effective than NRT – but are the other consequences of allowing the sale of e-cigarettes? E-cigarettes have proven popular with adolescents. Last year, Dr. Scott Gottlieb, moved to more carefully regulate them in late 2018.
Dr. Gottlieb, observing the “astonishing” surge in adolescent use of e-cigarettes, commented: “The reality is if we don’t prevent this level of youth use of these products, this is an existential risk for the entire industry. The alternative is to pull the products off the market, which is not something we want to do.”
- Many thanks to Dr. Peter Selby for helping me understand the Hajek et al. paper better.
- Smoking cessation has been considered in past Readings. For a Reading on smoking cessation and financial incentives, see: http://davidgratzer.com/reading-of-the-week/reading-of-the-week-smoking-cessation-incentives-the-nejm-paper/.
Reading of the Week. Every week I pick articles and papers from the world of Psychiatry.