e-cigarettes and smoking cessation, are they useful??

so, it turns out that there was a systematic review/meta-analysis last month in Lancet Respiratory Medicine on the use of e-cigarettes and smoking cessation (see smoking cessation ecigs metaanal lancetresp2016 in dropbox, or doi.org/10.1016/S2213-2600(15)00521-4). thanks, again, to karen henley for bringing this up to me, after i had mentioned in a blog earlier this week that i had a few patients who were able to quit smoking by using e-cigarettes after they had failed with the traditional medical therapies. as a review of this article:

--38 studies were included, including 20 with control groups.
--results:
    --odds of quitting cigarettes was 28% LOWER with e-cigarettes [OR 0.72 (0.57-0.91)]
    --the studies are a mixed bag and fraught with confounders (eg several just compared patients who were not interested in quitting but who used e-cigarettes vs those who did not, finding mixed results as to who quit later). looking at studies which included only smokers interested in quitting found a nonsignificant 16% lower likelihood of smoking cessation in e-cig users. one study found that the heavier users of e-cigarettes were more likely to quit than occasional users.
    --in fact, the only randomized controlled trial which compared e-cigarettes to nicotine patches (see smoking cessation ecigs vs patch lancet 2013 in dropbox, or Lancet 2013; 382: 1629) randomized 657 heavy smokers with mean of 18 cigarettes/d who wanted to quit smoking into 289 on nicotine e-cigs, 295 to nicotine patches, and 73 to placebo e-cigs. their results at 6 months was verified nicotine abstinence in 7.3% with nicotine e-cigarettes, 5.8% with patches, and 4.1% with placebo e-cigarettes. these numbers were well under the expected quit rate, and there was no statistical difference between the interventions. This trial was criticized because the e-cigarettes were provided to the patients, but those on patches only got a voucher for them. The only other clinical trial was nonrandomized (differentiated patients who were willing vs not willing to accept e-cigarettes), also finding a non-significant increase in smoking cessation with e-cigarettes.

so, a few points:
--this systematic review and meta-analysis brings out an interesting and not-so-uncommon issue: in the abstract of the article the authors present this study as pretty unequivocally showing "the odds of quitting cigarettes were 28% lower in those who used e-cigarettes", and that this was true pretty much regardless of the study design or subgroup analyses.  A pretty strong statement given that the largest group of studies involved patients who were not even trying to quit cigarettes (and those smoking e-cigarettes may have wanted even more nicotine) and their later comment (buried in the article), that if you evaluate only the studies of people wanting to quit, there was only a nonsignificant trend towards less quitting with e-cigs. They commented extensively at the end of the paper that there was no standard definition of smoking cessation, these were almost all observational studies (and the two cited above, closest to actual controlled studies, found NO difference and a trend to more smoking cessation with e-cigs), there were large differences in the quality of the studies or even the extent of e-cigarette use, most studies just had patient reports without confirmation of smoking cessation, and there was no assessment of the types or quality of the e-cigarette use reported. And, given the preponderance of potentially useful medical articles in huge numbers of journals (eg Lancet itself now has an array of more specialized journals, such as the one for this article), it is really important for the abstract to reflect the real and clinically-important conclusions of the study, and not rely on meticulous reading of the methodology and actually reviewing the content of several of the articles included in the systematic review, to get at the real issues. We just do not have enough time to try to keep up in the medical literature without having clear and accurate summaries.
--as noted in the article "no clinical trials have done a true head-to-head comparisons of e-cigarettes with standard therapies (ie, nicotine patch, gum, or inhaler) approved by the US FDA for smoking cessation". and this type of trial in the US is unlikely, since it would only be done if the e-cigarette makes requested approval by the FDA as an Investigational New Drug. Again, no mention of this rather compelling deficiency in the abstract, or on brief scan of the article.
--why might e-cigarettes not help? after all, they do emulate the actual process of smoking, which may be a very longterm behavioral response to stress, nicotine withdrawal, other social cues such as meeting with certain friends/drinking a beer etc. And therefore it seems to me that using e-cigs could be part of the gradual process of getting off cigarettes, and, as a good thing, they are less satisfying than cigarettes, per my patients, so getting off them may be easier later. one observation by the authors is e-cigs are not prescribed by clinicians. nicotine replacement therapy, when prescribed, seems to work (see prior blogs at http://gmodestmedblogs.blogspot.com/search/label/smoking%20cessation ), but this is not clearly the case when they are bought over-the-counter (see JAMA 2002; 288: 1260).
--is there a role for e-cigarettes in harm reduction? i would think so. much less toxic than cigarettes, which have on the order of 3000 chemical additives (there are certainly additives in e-cigarettes, including propylene glycol, as an emulsifier; several flavors such as vanilla, menthol; several chemicals to improve the smell such as 2-acetylpyridine and others; and none of these are regulated by the FDA since e-cigarettes are not a "drug", but are likely less toxic than the multitude of chemicals in cigarettes) . and, when my patients have used them, they usually take only 1-2 puffs and stop. so, i would guess, they often get much less inhaled nicotine.