Efficacy of e-cigarettes in smoking cessation

The evidence for e-cigarettes as smoking cessation aids is limited. A recent systematic review identified one randomised controlled trial that investigated the efficacy of e-cigarettes as an aid to tobacco smoking cessation in a population of adult smokers ‘motivated to quit’, and one trial in smokers ‘not motivated to quit’.11

A study of 657 people who had expressed a desire to quit randomised them to commercially-available e-cigarettes containing 16mg nicotine, 21mg nicotine patches or placebo e-cigarettes that contained no nicotine.12 All participants were offered telephone-based behavioural support. The researchers anticipated 6-month continuous tobacco abstinence rates (the primary outcome) of 15% for placebo e-cigarettes and 20% for nicotine patches. Unfortunately, quit rates were considerably lower, with the result that the study was underpowered to show a difference between the interventions (see Table 2).

A second study recruited 300 regular smokers who were not intending to quit to try an e-cigarette to reduce the risk of tobacco smoking.13 This proof-of-concept pilot study randomised smokers to an e-cigarette with cartridges containing 7.2mg nicotine for 12 weeks, an e-cigarette with cartridges containing 7.2mg nicotine for 6 weeks followed by cartridges containing 5.4mg nicotine for 6 weeks, or cartridges that did not contain nicotine for 12 weeks. Participants were not offered any form of behavioural support. The primary outcome was ≥50% reduction in the number of tobacco cigarettes/day since baseline. At week 52, excluding quitters, on an intention-to-treat basis 14.5% of those using nicotine-containing cartridges compared with 12% using no-nicotine cartridges achieved the primary outcome (p=0.55). The study reported 12-month continuous abstinence rates (a secondary outcome) of 9–13% with nicotine e-cigarettes, and 4% with placebo e-cigarettes, although the differences between the groups were not statistically significant.

Harm reduction?

Harm reduction has become an accepted strategy in recent years and the National Institute for Health and Care Excellence has published public health guidance on harm reduction strategies that recommends the use of licensed NRT products.14

Many researchers point to the potential role for e-cigarettes in harm reduction, helping smokers to reduce their tobacco intake. In the study of people not intending to quit, 10% of smokers reduced cigarette consumption by at least half over the course of 52 weeks while using a nicotine e-cigarette or a placebo e-cigarette.13 However, there was no statistically significant difference in reduction rates between the groups, suggesting that factors other than nicotine may play an important role in maintaining the habit of smoking.

Several other studies of varying quality demonstrate a reduction in the numbers of cigarettes smoked per day among users of e-cigarettes.15

However, the absolute health benefit of cutting down on tobacco consumption is difficult to quantify. While the effects of smoking cessation are well-documented, the evidence for smoking reduction is less clear. Not all studies show a significant survival benefit from smoking reduction. One recent review points out that the relationship between exposure to fine particles from smoking and developing cardiovascular disease is far from a linear dose-response.15 Even light smoking can markedly elevate the risk.

Finally, population-based studies call into question whether e-cigarettes are likely to help or hinder smokers wishing to stop. Several studies show e-cigarette users are not more likely to quit smoking tobacco than non-users.15 A meta-analysis of these studies show that ‘real world’ use of e-cigarettes may actually lower the odds of quitting cigarettes (pooled OR 0.61, 95% CI 0.50 to 0.75).15 The authors acknowledge that not all studies controlled for nicotine dependence, so the figures might be skewed by more highly dependent smokers choosing e-cigarettes for their quit attempts.

Safety concerns

Health and safety concerns are partly related to the situation regarding regulation of e-cigarettes. Studies demonstrate widely varying levels of nicotine among e-cigarettes labelled as being of the same strength, the presence of contaminants from other production processes (one study found traces of rimonabant and tadalafil) and a range of often unspecified food additives.8

There have been a small number of reports of e-cigarettes exploding and catching fire.10 This is a known, if rare, risk from lithium batteries. Safety information for inhalation of vapour formed from propylene glycol and glycerol comes mainly from its use in ‘smoke’ machines in the entertainment industry. High levels of exposure over a prolonged period can cause airways irritation. However, the US Food and Drug Administration (FDA) classifies them as ‘generally considered as safe’.8

An FDA analysis of cartridges of nicotine-containing liquid for e-cigarettes found traces of carcinogenic tobacco-specific nitrosamines.16 One cartridge also contained the toxic product diethylene glycol. Another analysis found that levels of nitrosamines were similar to those in an NRT patch.16 E-cigarette liquids and vapour have also been found to contain traces of metals (including tin, nickel, copper, lead and chromium), possibly resulting from contact with the heating elements in the e-cigarette.15

One potential danger from e-cigarettes is accidental ingestion of nicotine-containing liquid from cartridges, or its absorption through the skin or eyes.4 A further unknown factor is the effect of inhaling the flavourings in e-cigarettes. Food flavourings are approved for human consumption, but there are scant data about their effects when inhaled.8

Studies of the short-term effects of e-cigarette use report cough, sore throat, eye irritation, increased airways resistance and increased heart rate8 In the biggest clinical study to date, there were no significant differences in adverse events between people using nicotine e-cigarettes, placebo e-cigarettes and nicotine patches over a duration of 6 months.12 However, data on the long-term health effects of e-cigarette use are lacking.17

The view from some researchers seems to be that e-cigarettes, while they carry health risks that are not entirely known, are likely to be considerably safer than tobacco cigarettes.11

Public health issues

The proponents of e-cigarettes claim that they could save millions of lives, if sufficient numbers of smokers transfer their nicotine dependence to the supposedly less-harmful electronic cigarette.18 They argue that e-cigarette users are tobacco smokers already addicted to nicotine, and that substituting one method of accessing the drug with another that is less harmful, can only be good.

The vast majority of users are cigarette smokers, although the evidence that they will switch completely from tobacco to e-cigarettes is lacking. One review has highlighted high levels of dual use, suggesting that e-cigarettes could represent an additional health risk, not a substitute risk.15

Some long-term users report using larger devices, designed to provide more intense vapour, suggesting increased nicotine tolerance.17 A review of e-cigarette use among adolescents found increasing levels of use.19 Lifetime use in this age group in the USA rose rapidly, from <1–3.3% in 2011 to 6.8% in 2012, and 20% of adolescent e-cigarette users in one survey had never smoked tobacco. E-cigarette use among adolescent smokers was not strongly linked to a desire to give up smoking.

Some advocate that e-cigarette use should be banned wherever tobacco smoking is banned, partly to avoid the risk of re-normalisation.15 Others, including the UK anti-smoking pressure group Action on Smoking and Health, disagree, citing the lack of evidence for harm from passive inhalation of e-cigarette vapour.20

The authors of a recent editorial on potential harms concluded that there is little evidence for the main concerns about the safety of e-cigarettes, their effect on tobacco smoking in young people, or the threat they might act as a ‘gateway drug’ to tobacco cigarettes.21

A question of regulation

Although e-cigarettes are currently regulated as general consumer products they will be subject to additional regulatory rules. In April 2014, the European Parliament adopted a revised European Union Tobacco Products Directive (TPD), which will subject all e-cigarettes to new regulatory controls unless they fall under the definition of a medicinal product.22 The TPD will require manufacturers of e-cigarettes and refill containers to provide information on ingredients, emissions and nicotine uptake before the product is marketed. They will also need to report adverse events and provide sales information to the competent authority in each EU member state. Most e-cigarettes and refills are likely to fall into this regulatory category. However, higher strength products (>20mg/mL nicotine) will not be permitted under the TPD regime and will have to be licensed as a medicine.

In the UK there are two options for regulation of e-cigarettes:

• as consumer products under the EU Tobacco Products Directive

• as medicinal products for smoking cessation and reduction

Marketing authorisation will be required for e-cigarettes that make a medicinal claim for “cutting down, quitting and reducing the harms of smoking”. The Medicines and Healthcare products Regulatory Agency (MHRA) will be responsible for regulating all NRT (including e-cigarettes) considered to be medicinal products, and the licensing process will involve an assessment of quality, safety and efficacy. Companies are being encouraged by the MHRA to submit applications for nicotine-containing products and has issued guidance on the licensing of e-cigarettes.24 The MHRA has advised that assessment of efficacy could be based on a pharmacokinetic study comparing the new product to an appropriate reference medicinal product (e.g. Nicorette Inhalator) and a pharmacodynamic assessment (e.g. assessment of craving for nicotine).24,25 E-cigarettes regulated as medicines will require a Risk Management Plan that will encourage research into e-cigarette efficacy and safety for smoking cessation.23–25 Any e-cigarette licensed as a medicine can be promoted within the medicines regulatory framework in line with the licensed indication. Products that have marketing authorisation could be recommended to those who seek advice through smoking cessation clinics in line with national guidance.23–25 E-cigarettes could be granted General Sales List status (GSL) and sold over-the-counter in pharmacies and general sales outlets in the same way as some other NRT products.

In the UK it is likely that the majority of e-cigarettes will be marketed as consumer products under EU law. It is not known how the price of e-cigarettes that are marketed as consumer products will compare with those that are medicinal products.

The Royal Pharmaceutical Society has issued a position statement on e-cigarettes and recommends that they should not currently be sold or advertised from pharmacies.26

New rules on advertising of e-cigarettes come into effect in November 2014 and will apply to broadcast and non-broadcast marketing.27 Advertisements must be ‘socially responsible’, make clear that e-cigarettes are not tobacco products and must state if the product contains nicotine. In addition, advertisements must not contain health or medicinal claims unless the product is authorised for such purposes by the MHRA.