PMID- 36384212 OWN - NLM STAT- MEDLINE DCOM- 20221121 LR - 20240306 IS - 1469-493X (Electronic) IS - 1361-6137 (Linking) VI - 11 IP - 11 DP - 2022 Nov 17 TI - Electronic cigarettes for smoking cessation. PG - CD010216 LID - 10.1002/14651858.CD010216.pub7 [doi] LID - CD010216 AB - BACKGROUND: Electronic cigarettes (ECs) are handheld electronic vaping devices which produce an aerosol by heating an e-liquid. Some people who smoke use ECs to stop or reduce smoking, although some organizations, 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 smoking, and if they are safe to use for this purpose. This is a review update conducted as part of a living systematic review. OBJECTIVES: To examine the effectiveness, tolerability, and safety of using electronic cigarettes (ECs) to help people who smoke tobacco 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 to 1 July 2022, and reference-checked and contacted 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. Studies had to report abstinence from cigarettes at six months or longer or data on safety markers at one week or longer, or both. 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, adverse events (AEs), and serious adverse events (SAEs). Secondary outcomes included the proportion of people still using study product (EC or pharmacotherapy) at six or more months after randomization or starting EC use, changes in carbon monoxide (CO), blood pressure (BP), heart rate, arterial oxygen saturation, lung function, and levels of carcinogens or toxicants, or both. We used a fixed-effect Mantel-Haenszel model to calculate risk ratios (RRs) with a 95% confidence interval (CI) for dichotomous outcomes. For continuous outcomes, we calculated mean differences. Where appropriate, we pooled data in meta-analyses. MAIN RESULTS: We included 78 completed studies, representing 22,052 participants, of which 40 were RCTs. Seventeen of the 78 included studies were new to this review update. Of the included studies, we rated ten (all but one contributing to our main comparisons) at low risk of bias overall, 50 at high risk overall (including all non-randomized studies), and the remainder at unclear risk. There was high certainty that quit rates were higher in people randomized to nicotine EC than in those randomized to nicotine replacement therapy (NRT) (RR 1.63, 95% CI 1.30 to 2.04; I(2) = 10%; 6 studies, 2378 participants). In absolute terms, this might translate to an additional four quitters per 100 (95% CI 2 to 6). There was moderate-certainty evidence (limited by imprecision) that the rate of occurrence of AEs was similar between groups (RR 1.02, 95% CI 0.88 to 1.19; I(2) = 0%; 4 studies, 1702 participants). SAEs were rare, but there was insufficient evidence to determine whether rates differed between groups due to very serious imprecision (RR 1.12, 95% CI 0.82 to 1.52; I(2) = 34%; 5 studies, 2411 participants). There was moderate-certainty evidence, limited by imprecision, that quit rates were higher in people randomized to nicotine EC than to non-nicotine EC (RR 1.94, 95% CI 1.21 to 3.13; I(2) = 0%; 5 studies, 1447 participants). In absolute terms, this might lead to an additional seven quitters per 100 (95% CI 2 to 16). There was moderate-certainty evidence of no difference in the rate of AEs between these groups (RR 1.01, 95% CI 0.91 to 1.11; I(2) = 0%; 5 studies, 1840 participants). There was insufficient evidence to determine whether rates of SAEs differed between groups, due to very serious imprecision (RR 1.00, 95% CI 0.56 to 1.79; I(2) = 0%; 8 studies, 1272 participants). Compared to behavioural support only/no support, quit rates were higher for participants randomized to nicotine EC (RR 2.66, 95% CI 1.52 to 4.65; I(2) = 0%; 7 studies, 3126 participants). In absolute terms, this represents an additional two quitters per 100 (95% CI 1 to 3). However, this finding was of very low certainty, due to issues with imprecision and risk of bias. There was some evidence that (non-serious) AEs were more common in people randomized to nicotine EC (RR 1.22, 95% CI 1.12 to 1.32; I(2) = 41%, low certainty; 4 studies, 765 participants) and, again, insufficient evidence to determine whether rates of SAEs differed between groups (RR 1.03, 95% CI 0.54 to 1.97; I(2) = 38%; 9 studies, 1993 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 with continued EC use. Very few studies reported data on other outcomes or comparisons, hence evidence for these is limited, with CIs often encompassing clinically significant harm and benefit. AUTHORS' CONCLUSIONS: There is high-certainty evidence that ECs with nicotine increase quit rates compared to NRT and moderate-certainty evidence that they increase quit rates compared to ECs without nicotine. Evidence comparing nicotine EC with usual care/no treatment also suggests benefit, but is less certain. More studies are needed to confirm the effect size. Confidence intervals were for the most part wide for data on AEs, SAEs and other safety markers, with no difference in AEs between nicotine and non-nicotine ECs nor between nicotine ECs and NRT. Overall incidence of SAEs was low across all study arms. We did not detect evidence of serious harm from nicotine EC, but longest follow-up was two years and the 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, but further RCTs are underway. To ensure the review continues to provide up-to-date information to decision-makers, this review is a living systematic review. We run searches monthly, with the review updated when relevant new evidence becomes available. Please refer to the Cochrane Database of Systematic Reviews for the review's current status. CI - Copyright (c) 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. FAU - Hartmann-Boyce, Jamie AU - Hartmann-Boyce J AD - Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK. FAU - Lindson, Nicola AU - Lindson N AD - Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK. FAU - Butler, Ailsa R AU - Butler AR AD - Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK. FAU - McRobbie, Hayden AU - McRobbie H AD - National Drug and Alcohol Research Centre, University of New South Wales, Sydney, Australia. FAU - Bullen, Chris AU - Bullen C AD - National Institute for Health Innovation, University of Auckland, Auckland, New Zealand. FAU - Begh, Rachna AU - Begh R AD - Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK. FAU - Theodoulou, Annika AU - Theodoulou A AD - Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK. FAU - Notley, Caitlin AU - Notley C AD - Norwich Medical School, University of East Anglia, Norwich, UK. FAU - Rigotti, Nancy A AU - Rigotti NA AD - Tobacco Research and Treatment Center, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. FAU - Turner, Tari AU - Turner T AD - Cochrane Australia, School of Public Health & Preventive Medicine, Monash University, Melbourne, Australia. FAU - Fanshawe, Thomas R AU - Fanshawe TR AD - Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK. FAU - Hajek, Peter AU - Hajek P AD - Wolfson Institute of Preventive Medicine, Barts & The London School of Medicine and Dentistry, Queen Mary University of London, London, UK. LA - eng GR - 23875/CRUK_/Cancer Research UK/United Kingdom GR - 29845/CRUK_/Cancer Research UK/United Kingdom GR - PG/15/64/31681/BHF_/British Heart Foundation/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PT - Systematic Review DEP - 20221117 PL - England TA - Cochrane Database Syst Rev JT - The Cochrane database of systematic reviews JID - 100909747 RN - 0 (Nicotinic Agonists) RN - 6M3C89ZY6R (Nicotine) SB - IM UOF - Cochrane Database Syst Rev. 2021 Sep 14;9:CD010216. PMID: 34519354 CIN - J Prim Health Care. 2022 Dec;14(4):378-379. PMID: 36592778 UIN - Cochrane Database Syst Rev. 2024 Jan 8;1:CD010216. PMID: 38189560 MH - Humans MH - *Smoking Cessation/methods MH - *Electronic Nicotine Delivery Systems MH - Tobacco Use Cessation Devices MH - Nicotinic Agonists/therapeutic use MH - Systematic Reviews as Topic MH - Nicotine/adverse effects MH - Randomized Controlled Trials as Topic PMC - PMC9668543 COIS- RB holds an NIHR grant, but this did not directly fund this current work. She is principal investigator of an ongoing study listed in this review. CB was principal investigator on the ASCEND e-cigarette trial reported in the Cochrane Review and a co-investigator on the ASCEND II trial and several other studies included in the review. CB has provided consultancy for J&J KK (Japan) on NRT products. CB reports research grants from the Health Research Council of NZ, the Heart Foundation of NZ and the NZ Ministry of Health. He has recently led a project funded by Pfizer (NZ) on chronic disease management. ARB's work on this review has been supported by Cancer Research UK Project Award funding. This is not deemed a conflict of interest. TF has no known conflicts of interest. PH provided consultancy for and received research funding from Pfizer, a manufacturer of stop-smoking medications. He was principal investigator on one of the trials included in this review and co-investigator on other relevant studies. JHB has received support for this work from the Cochrane Review Support Programme and the University of Oxford's Returning Carer's Fund. Neither of these are deemed conflicts of interest. NL has received payment for lectures on systematic review methodology, and has been an applicant on project funding to carry out priority setting and systematic reviews in the area of tobacco control (NIHR funded). None of this is deemed a conflict of interest. HM has no known conflicts of interest. CN has no known conflicts of interest. NAR has received royalties from UpToDate, Inc., for chapters on electronic cigarettes and occasional fees from academic hospitals or professional medical societies for lectures on smoking cessation that include discussion of electronic cigarettes. NAR was a member of the committee that produced the 2018 National Academies of Science, Engineering, and Medicine's Consensus Study Report on the Public Health Benefits of E-cigarettes. She was unpaid for this work. Outside the topic of e-cigarettes, NAR is a consultant for Achieve LifeSciences, which is developing an investigational smoking cessation medication for FDA approval (cytisine) and her institution (MGH) receives a grant from the company as a site for a clinical trial testing the safety and efficacy of cytisine. NAR holds grants from NIH for research work. AT's work on this review has been supported by the Cochrane Review Support Programme and the University of Oxford's Returning Carer's Fund. Neither of these are deemed conflicts of interest. TT has no known conflicts of interest. EDAT- 2022/11/18 06:00 MHDA- 2022/11/22 06:00 PMCR- 2023/11/17 CRDT- 2022/11/17 09:31 PHST- 2022/11/17 09:31 [entrez] PHST- 2022/11/18 06:00 [pubmed] PHST- 2022/11/22 06:00 [medline] PHST- 2023/11/17 00:00 [pmc-release] AID - CD010216.pub7 [pii] AID - 10.1002/14651858.CD010216.pub7 [doi] PST - epublish SO - Cochrane Database Syst Rev. 2022 Nov 17;11(11):CD010216. doi: 10.1002/14651858.CD010216.pub7.