E-cigarettes more likely to lead to ongoing nicotine addiction than NRT

E-cigarette advocates and, more important, the FDA, takes it as given that e-cigarettes were developed as a harm reduction tool to help smokers quit cigarettes by “switching completely.” 

This assumption is, however, inconsistent with the tobacco companies’ actual reasons for developing e-cigarettes and other non-combustible products, including tobacco company products approved as NRT: To deter health-concerned smokers from leaving the tobacco market entirely. 

The new paper “E-cigarettes and nicotine abstinence: a meta-analysis of randomised controlled trials” by Reiner Hanewinkel and colleagues shows how successful this strategy has been for the tobacco companies.  They did a meta-analysis (quantitative summary) of the four randomized trials that did head-to-head comparisons of NRT and e-cigarettes for smoking cessation and, like earlier meta-analyses of RCTs on this question, found that, at least at the end of the relatively short trial periods,  e-cigarette users stopped smoking cigarettes more than smokers randomized to receive NRT (risk ratio 1.58 (95% CI 1.20–2.08)).

But then they went a step further and asked about cessation of all nicotine use.  None of the trials reported this result so they contacted the study authors and asked for that information.  Three of the 4 study lead authors provided the information.  In contrast to the results for stopping smoking, e-cigarette were only half as likely to have stopped all nicotine use (risk ratio 0.50 (95% CI 0.32–0.77)).

Here is how they describe the implications:

The data from these studies suggest that for every 100 people using e-cigarettes to stop smoking, 14 or 15 might successfully quit, but 10 or 11 of them will continue using e-cigarettes; whereas only nine out of 100 people might quit using NRTs, but only two of them will continue using nicotine.

Results of a recent Cochrane review and other systematic reviews and meta-analyses indicating a therapeutic effect of e-cigarettes have been replicated by the present study. However, our study is the first to show that the use of e-cigarettes as a therapeutic intervention may have a negative effect on nicotine abstinence in RCTs compared to NRTs. In other words, most of the smokers who quit smoking with the help of e-cigarettes continue to use e-cigarettes until the end of the observational period of the RCTs. …

Our findings suggest that for every 100 people using e-cigarettes to stop smoking, only four might successfully quit and abstain from nicotine, compared with seven per 100 people in the NRT group. In such a way, a few systematic reviews demonstrated that there is an increased risk of subsequent combustible smoking initiation and smoking relapse among users of e-cigarettes. A substantial number of individuals using e-cigarettes as a cessation device may initiate dual use of e-cigarettes and combustible tobacco, which is the most common use pattern, and probably riskier for health than using tobacco or e-cigarettes alone.  [citations dropped, emphasis added]

It is important to keep in mind that these results are for clinical trials in which the results are most likely to be most favorable because of the highly controlled environment.  A population study of thousands of that followed thousands of smokers forward in time for 3 years found similar results: e-cigarette users were very unlikely to stop nicotine use entirely (aRRR: 0.17, 95% CI:0.09–0.32) and likely to continue using e-cigarettes.

As noted above, this is precisely why the tobacco companies developed e-cigarettes and related products well before they were developed in China.  This is even true for NRT unless it is properly used as part of a smoking cessation program.  As Dorie Apollonio and I reported in our paper “Tobacco Industry Research on Nicotine Replacement Therapy: If Anyone Is Going to Take Away Our Business It Should Be Us”:

…In the 1990s, industry-internal research found that many smokers were using NRT to supplement smoking or in lieu of quitting outright. After the FDA began regulating cigarettes in 2009, tobacco companies launched their own nicotine product lines, which they defined as a single category that included nicotine gum, patches, lozenges, and e-cigarettes.

Major tobacco companies in the United States and the United Kingdom viewed NRT, even when it was only available by prescription, as a recreational product that could maintain and possibly expand the use of nicotine as smoking became less socially acceptable. Although NRT was approved for cessation, tobacco industry research found in the early 1990s that many smokers used it in combination with  cigarettes and that smokers who used NRT for cessation would otherwise have quit outright.

Tobacco industry research from the 1970s forward treated all products containing nicotine—including cigarettes, e-cigarettes and their precursors, and others (e.g., gums, patches, and candy)—as part of a single market: the nicotine delivery, or Craving Relief market. Industry marketing anticipates that noncigarette nicotine delivery products will be used by smokers for whom smoking is unacceptable, thus facilitating and normalizing lifelong nicotine addiction.

A presentation from senior executives at Atria (owners of Philip Morris Tobacco) to investors in February 2022 highlighted how the presence of non-cigarette products was helping to maintain total sales (see slide at the top of this blog post and accompanying text).  Note that the slide depicts total sales not individual behavior; dual users would be represented in the sales of all products that they purchase.

It is long past time for researchers and regulators – most notably the FDA – to recognize this history and reality rather than clinging to the illusion that e-cigarettes and other new products were developed to reduce harm.  That may be the framing the tobacco companies are now using to win approvals and sell these products.  But it is far from the underlying business and health harm reality.

Here is the abstract of the new Hanewinkel et al paper:

Objectives To determine the effects of electronic cigarettes (e-cigarettes) as a therapeutic intervention compared to nicotine replacement therapy (NRT) on nicotine abstinence.

Methods Two authors independently searched the PubMed, Embase, PsycInfo and Cochrane Central Register of Controlled Trials databases for articles published up to and including 10 July 2021. We included randomised controlled trials (RCTs) in which nicotine e-cigarettes were compared to NRT among current cigarette users. The primary outcome was abstaining from all nicotine-delivery devices. Secondary outcomes were 1) allocated product use (e-cigarettes or NRT) among successful cigarette quitters and 2) quitting cigarettes at the end of the trial using fixed-effect Mantel–Haenszel models.

Results We included four RCTs representing 1598 adult participants (51.0% females). The mean age of participants in these studies ranged from 41 to 54 years, while average baseline smoking ranged from 14 to 21 cigarettes per day. Compared to NRT, e-cigarette use was associated with lower nicotine abstinence rates at the longest follow-up (risk ratio 0.50 (95% CI 0.32–0.77)). Among successful cigarette quitters, the risk of allocated product use by the end of the observational time was higher for e-cigarette users compared to NRT (risk ratio 8.94 (95% CI 3.98–20.07)). E-cigarette users had higher cigarette smoking cessation rates compared to NRT users (risk ratio 1.58 (95% CI 1.20–2.08)).

Conclusions The use of e-cigarettes as a therapeutic intervention for smoking cessation may lead to permanent nicotine dependence.

The full citation is: Hanewinkel R, Niederberger K, Pedersen A, Unger JB, Galimov A. E-cigarettes and nicotine abstinence: a meta-analysis of randomised controlled trials. Eur Respir Rev. 2022 Mar 23;31(163):210215. doi: 10.1183/16000617.0215-2021. PMID: 35321930.  It is available here.

Published by Stanton Glantz

Stanton Glantz is a retired Professor of Medicine who served on the University of California San Francisco faculty for 45 years. He conducts research on tobacco and cannabis control and cardiovascular disease/

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