Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. BACKGROUND: Electronic cigarettes (ECs) are handheld electronic vaping devices which produce an aerosol formed by heating an e-liquid. People who smoke report using ECs to stop or reduce smoking, but some organisations, advocacy groups and policymakers have discouraged this, citing lack of evidence of efficacy and safety. People who smoke, healthcare providers and regulators want to know if ECs can help people quit and if they are safe to use for this purpose. This review is an update of a review first published in 2014. OBJECTIVES: To evaluate the effect and safety of using electronic cigarettes (ECs) to help people who smoke achieve long-term smoking abstinence. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group's Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and PsycINFO for relevant records to January 2020, together with reference-checking and contact with study authors. SELECTION CRITERIA: We included randomized controlled trials (RCTs) and randomized cross-over trials in which people who smoke were randomized to an EC or control condition. We also included uncontrolled intervention studies in which all participants received an EC intervention. To be included, studies had to report abstinence from cigarettes at six months or longer and/or data on adverse events (AEs) or other markers of safety at one week or longer. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods for screening and data extraction. Our primary outcome measures were abstinence from smoking after at least six months follow-up, AEs, and serious adverse events (SAEs). Secondary outcomes included changes in carbon monoxide, blood pressure, heart rate, blood oxygen saturation, lung function, and levels of known carcinogens/toxicants. We used a fixed-effect Mantel-Haenszel model to calculate the risk ratio (RR) with a 95% confidence interval (CI) for dichotomous outcomes. For continuous outcomes, we calculated mean differences. Where appropriate, we pooled data from these studies in meta-analyses. MAIN RESULTS: We include 50 completed studies, representing 12,430 participants, of which 26 are RCTs. Thirty-five of the 50 included studies are new to this review update. Of the included studies, we rated four (all which contribute to our main comparisons) at low risk of bias overall, 37 at high risk overall (including the 24 non-randomized studies), and the remainder at unclear risk. There was moderate-certainty evidence, limited by imprecision, that quit rates were higher in people randomized to nicotine EC than in those randomized to nicotine replacement therapy (NRT) (risk ratio (RR) 1.69, 95% confidence interval (CI) 1.25 to 2.27; I2 = 0%; 3 studies, 1498 participants). In absolute terms, this might translate to an additional four successful quitters per 100 (95% CI 2 to 8). There was low-certainty evidence (limited by very serious imprecision) of no difference in the rate of adverse events (AEs) (RR 0.98, 95% CI 0.80 to 1.19; I2 = 0%; 2 studies, 485 participants). SAEs occurred rarely, with no evidence that their frequency differed between nicotine EC and NRT, but very serious imprecision led to low certainty in this finding (RR 1.37, 95% CI 0.77 to 2.41: I2 = n/a; 2 studies, 727 participants). There was moderate-certainty evidence, again limited by imprecision, that quit rates were higher in people randomized to nicotine EC than to non-nicotine EC (RR 1.71, 95% CI 1.00 to 2.92; I2 = 0%; 3 studies, 802 participants). In absolute terms, this might again lead to an additional four successful quitters per 100 (95% CI 0 to 12). These trials used EC with relatively low nicotine delivery. There was low-certainty evidence, limited by very serious imprecision, that there was no difference in the rate of AEs between these groups (RR 1.00, 95% CI 0.73 to 1.36; I2 = 0%; 2 studies, 346 participants). There was insufficient evidence to determine whether rates of SAEs differed between groups, due to very serious imprecision (RR 0.25, 95% CI 0.03 to 2.19; I2 = n/a; 4 studies, 494 participants). Compared to behavioural support only/no support, quit rates were higher for participants randomized to nicotine EC (RR 2.50, 95% CI 1.24 to 5.04; I2 = 0%; 4 studies, 2312 participants). In absolute terms this represents an increase of six per 100 (95% CI 1 to 14). However, this finding was very low-certainty, due to issues with imprecision and risk of bias. There was no evidence that the rate of SAEs varied, but some evidence that non-serious AEs were more common in people randomized to nicotine EC (AEs: RR 1.17, 95% CI 1.04 to 1.31; I2 = 28%; 3 studies, 516 participants; SAEs: RR 1.33, 95% CI 0.25 to 6.96; I2 = 17%; 5 studies, 842 participants). Data from non-randomized studies were consistent with RCT data. The most commonly reported AEs were throat/mouth irritation, headache, cough, and nausea, which tended to dissipate over time with continued use. Very few studies reported data on other outcomes or comparisons and hence evidence for these is limited, with confidence intervals often encompassing clinically significant harm and benefit. AUTHORS' CONCLUSIONS: There is moderate-certainty evidence that ECs with nicotine increase quit rates compared to ECs without nicotine and compared to NRT. Evidence comparing nicotine EC with usual care/no treatment also suggests benefit, but is less certain. More studies are needed to confirm the degree of effect, particularly when using modern EC products. Confidence intervals were wide for data on AEs, SAEs and other safety markers. Overall incidence of SAEs was low across all study arms. We did not detect any clear evidence of harm from nicotine EC, but longest follow-up was two years and the overall number of studies was small. The main limitation of the evidence base remains imprecision due to the small number of RCTs, often with low event rates. Further RCTs are underway. To ensure the review continues to provide up-to-date information for decision-makers, this review is now a living systematic review. We will run searches monthly from December 2020, with the review updated as relevant new evidence becomes available. Please refer to the Cochrane Database of Systematic Reviews for the review's current status.

Electronic cigarettes for smoking cessation

https://www.thelancet.com/pdfs/journals/lanres/PIIS2213-2600(15)00521-4.pdf

E-cigarettes and smoking cessation in real-world and clinical settings: a systematic review and meta-analysis

Background: Electronic cigarettes (e-cigarettes) are becoming increasingly popular with smokers worldwide. Users report buying them to help quit smoking, to reduce cigarette consumption, to relieve tobacco withdrawal symptoms, and to continue having a ‘smoking’ experience, but with reduced health risks. Research on e-cigarettes is urgently needed in order to ensure that the decisions of regulators, healthcare providers and consumers are based on science. Methods ECLAT is a prospective 12-month randomized, controlled trial that evaluates smoking reduction/abstinence in 300 smokers not intending to quit experimenting two different nicotine strengths of a popular e-cigarette model (‘Categoria’; Arbi Group Srl, Italy) compared to its non-nicotine choice. GroupA (n=100) received 7.2 mg nicotine cartridges for 12 weeks; GroupB (n=100), a 6-week 7.2 mg nicotine cartridges followed by a further 6-week 5.4 mg nicotine cartridges; GroupC (n=100) received no-nicotine cartridges for 12 weeks. The study consisted of nine visits during which cig/day use and exhaled carbon monoxide (eCO) levels were measured. Smoking reduction and abstinence rates were calculated. Adverse events and product preferences were also reviewed. Results: Declines in cig/day use and eCO levels were observed at each study visits in all three study groups (p,0.001 vs baseline), with no consistent differences among study groups. Smoking reduction was documented in 22.3% and 10.3% at week-12 and week-52 respectively. Complete abstinence from tobacco smoking was documented in 10.7% and 8.7% at week-12 and week-52 respectively. A substantial decrease in adverse events from baseline was observed and withdrawal symptoms were infrequently reported during the study. Participants’ perception and acceptance of the product under investigation was satisfactory. Conclusion: In smokers not intending to quit, the use of e-cigarettes, with or without nicotine, decreased cigarette consumption and elicited enduring tobacco abstinence without causing significant side effects. Trial Registration: ClinicalTrials.gov NCT01164072

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EffiCiency and Safety of an eLectronic cigAreTte (ECLAT) as tobacco cigarettes substitute: a prospective 12-month randomized control design study

Electronic Nicotine Delivery Systems: International Tobacco Control Four-Country Survey

© 2014 The Cochrane Collaboration. Background: Electronic cigarettes (ECs) are electronic devices that heat a liquid - usually comprising propylene glycol and glycerol, with or without nicotine and flavours, stored in disposable or refillable cartridges or a reservoir - into an aerosol for inhalation. Since ECs appeared on the market in 2006 there has been a steady growth in sales. Smokers report using ECs to reduce risks of smoking, but some healthcare organisations have been reluctant to encourage smokers to switch to ECs, citing lack of evidence of efficacy and safety. Smokers, healthcare providers and regulators are interested to know if these devices can reduce the harms associated with smoking. In particular, healthcare providers have an urgent need to know what advice they should give to smokers enquiring about ECs. Objectives: To examine the efficacy of ECs in helping people who smoke to achieve long-term abstinence; to examine the efficacy of ECs in helping people reduce cigarette consumption by at least 50% of baseline levels; and to assess the occurrence of adverse events associated with EC use. Search methods: We searched the Cochrane Tobacco Addiction Groups Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and two other databases for relevant records from 2004 to July 2014, together with reference checking and contact with study authors. Selection criteria: We included randomized controlled trials (RCTs) in which current smokers (motivated or unmotivated to quit) were randomized to EC or a control condition, and which measured abstinence rates or changes in cigarette consumption at six months or longer. As the field of EC research is new, we also included cohort follow-up studies with at least six months follow-up. We included randomized cross-over trials and cohort follow-up studies that included at least one week of EC use for assessment of adverse events. Data collection and analysis: One review author extracted data from the included studies and another checked them. Our main outcome measure was abstinence from smoking after at least six months follow-up, and we used the most rigorous definition available (continuous, biochemically validated, longest follow-up). For reduction we used a dichotomous approach (no change/reduction < 50% versus reduction by 50% or more of baseline cigarette consumption). We used a fixed-effect Mantel-Haenszel model to calculate the risk ratio (RR) with a 95% confidence interval (CI) for each study, and where appropriate we pooled data from these studies in meta-analyses. Main results: Our search identified almost 600 records, from which we include 29 representing 13 completed studies (two RCTs, 11 cohort). We identified nine ongoing trials. Two RCTs compared EC with placebo (non-nicotine) EC, with a combined sample size of 662 participants. One trial included minimal telephone support and one recruited smokers not intending to quit, and both used early EC models with low nicotine content. We judged the RCTs to be at low risk of bias, but under the GRADE system the overall quality of the evidence for our outcomes was rated 'low' or 'very low' because of imprecision due to the small number of trials. A 'low' grade means that further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. A 'very low' grade means we are very uncertain about the estimate. Participants using an EC were more likely to have abstained from smoking for at least six months compared with participants using placebo EC (RR 2.29, 95% CI 1.05 to 4.96; placebo 4% versus EC 9%; 2 studies; GRADE: low). The one study that compared EC to nicotine patch found no significant difference in six-month abstinence rates, but the confidence intervals do not rule out a clinically important difference (RR 1.26, 95% CI: 0.68 to 2.34; GRADE: very low). A higher number of people were able to reduce cigarette consumption by at least half with ECs compared with placebo ECs (RR 1.31, 95% CI 1.02 to 1.68, 2 studies; placebo: 27% versus EC: 36%; GRADE: low) and compared with patch (RR 1.41, 95% CI 1.20 to 1.67, 1 study; patch: 44% versus EC: 61%; GRADE: very low). Unlike smoking cessation outcomes, reduction results were not biochemically verified. None of the RCTs or cohort studies reported any serious adverse events (SAEs) that were considered to be plausibly related to EC use. One RCT provided data on the proportion of participants experiencing any adverse events. Although the proportion of participants in the study arms experiencing adverse events was similar, the confidence intervals are wide (ECs vs placebo EC RR 0.97, 95% CI 0.71 to 1.34; ECs vs patch RR 0.99, 95% CI 0.81 to 1.22). The other RCT reported no statistically significant difference in the frequency of AEs at three- or 12-month follow-up between the EC and placebo EC groups, and showed that in all groups the frequency of AEs (with the exception of throat irritation) decreased significantly over time. Authors' conclusions: There is evidence from two trials that ECs help smokers to stop smoking long-term compared with placebo ECs. However, the small number of trials, low event rates and wide confidence intervals around the estimates mean that our confidence in the result is rated 'low' by GRADE standards. The lack of difference between the effect of ECs compared with nicotine patches found in one trial is uncertain for similar reasons. ECs appear to help smokers unable to stop smoking altogether to reduce their cigarette consumption when compared with placebo ECs and nicotine patches, but the above limitations also affect certainty in this finding. In addition, lack of biochemical assessment of the actual reduction in smoke intake further limits this evidence. No evidence emerged that short-term EC use is associated with health risk.

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Electronic cigarettes for smoking cessation and reduction

http://www.stop-tabac.ch/fr/images/stories/documents_stop_tabac/seigel%20e%20cigs%20am%20j%20prev%20med%202011.pdf

Kerry L. Tanwar

Papers

Electronic cigarettes as a smoking-cessation: tool results from an online survey.