RCT comparing e-cigs to NRT shows effectiveness in a supervised smoking cessation program: what it does and does not mean

Peter Hajek and colleagues published “A Randomized Trial of E-cigarettes versus Nicotine-Replacement Therapy” in the New England Journal of Medicine.  This is a well-done trial comparing e-cigarettes with nicotine replacement therapy among people enrolled in smoking cessation programs in England.  In addition to being randomized to e-cigs or NRT, people in the study had ar least 4 weeks of counselling.  At one year the cigarette abstinence rate was 18.0% among patients randomized to e-cigs compared to 9.9% randomized to NRT, nearly a doubling of quitting.

The study is thoughtfully designed and cautiously interpreted.  The authors also did a nice set of sensitivity analyses to show that the results are robust to the usual kinds of problems one has in doing a randomized controlled trial.

They conclude that “E-cigarettes were more effective for smoking cessation that nicotine-replacement therapy, when both products were accompanied by behavioural support.”  I agree with that conclusion.

Having said that, it is important to emphasize that this is not a study of e-cigarettes as most people use them, which is as recreational products not as part of a clinically supervised cessation attempt that, most important, includes intensive counselling.   Thus, the results of the Hajek study do not contradict the overall result that, in the general population, smokers who use e-cigarettes are, on average, less likely to quit smoking.

So, my bottom line is that if other well-done randomized controlled trials show that e-cigarettes improve smoking cessation, the manufacturers should submit the evidence to the appropriate authorities (the FDA in the USA) to get e-cigarettes approved as prescription medicines to be administered by physicians or other health professionals as part of supervised cessation efforts that include intensive counselling. 

The reason that I say they should be available by prescription is because of their high abuse potential, as evidenced by the run-away use of them by kids as well as the fact that when used unsupervised in the general population they depress smoking cessation.

In addition to efficacy, the drug approval process needs to assess safety.  Hajek and colleagues reported that after one year 80% of the e-cigarette group were still using e-cigarettes compared to just 9% of the NRT group were continuing to use NRT.  This is of particular concern because of the evidence linking e-cigarette use to heart attacks and chronic obstructive pulmonary disease and is something that warrants serious consideration by regulatory authorities.

The accompanying editorial by Belinda Borrelli and George T. O’Connor also raises several concerns about long-term safety of e-cigarette use and notes that varenicline -- which was not evaluated in the Hajek study -- outperforms NRT.

Here is the abstract:

BACKGROUND:  E-cigarettes are commonly used in attempts to stop smoking, but evidence is limited regarding their effectiveness as compared with that of nicotine products approved as smoking-cessation treatments.

METHODS: We randomly assigned adults attending U.K. National Health Service stop-smoking services to either nicotine-replacement products of their choice, including product combinations, provided for up to 3 months, or an e-cigarette starter pack (a second-generation refillable e-cigarette with one bottle of nicotine e-liquid [18 mg per milliliter]), with a recommendation to purchase further e-liquids of the flavor and strength of their choice. 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. Participants who were lost to follow-up or did not provide biochemical validation were considered to not be abstinent. Secondary outcomes included participant-reported treatment usage and respiratory symptoms.

RESULTS: A total of 886 participants underwent randomization. The 1-year abstinence rate was 18.0% in the e-cigarette group, as compared with 9.9% in the nicotine-replacement group (relative risk, 1.83; 95% confidence interval [CI], 1.30 to 2.58; P<0.001). Among participants with 1-year abstinence, those in the e-cigarette group were more likely than those in the nicotine-replacement group to use their assigned product at 52 weeks (80% [63 of 79 participants] vs. 9% [4 of 44 participants]). Overall, throat or mouth irritation was reported more frequently in the e-cigarette group (65.3%, vs. 51.2% in the nicotine-replacement group) and nausea more frequently in the nicotine-replacement group (37.9%, vs. 31.3% in the e-cigarette group). The e-cigarette group reported greater declines in the incidence of cough and phlegm production from baseline to 52 weeks than did the nicotine-replacement group (relative risk for cough, 0.8; 95% CI, 0.6 to 0.9; relative risk for phlegm, 0.7; 95% CI, 0.6 to 0.9). There were no significant between-group differences in the incidence of wheezing or shortness of breath.

CONCLUSIONS:  E-cigarettes were more effective for smoking cessation than nicotine-replacement therapy, when both products were accompanied by behavioral support. (Funded by the National Institute for Health Research and Cancer Research UK; Current Controlled Trials number, ISRCTN60477608 .).

The full citation is Hajek P, et al.  A Randomized Trial of E-Cigarettes versus Nicotine-Replacement Therapy.  N Engl J Med. 2019 Jan 30. doi: 10.1056/NEJMoa1808779. [Epub ahead of print].   The paper is available here.