PMID- 34519354 OWN - NLM STAT- MEDLINE DCOM- 20211124 LR - 20240210 IS - 1469-493X (Electronic) IS - 1361-6137 (Linking) VI - 9 IP - 9 DP - 2021 Sep 14 TI - Electronic cigarettes for smoking cessation. PG - CD010216 LID - 10.1002/14651858.CD010216.pub6 [doi] LID - CD010216 AB - BACKGROUND: Electronic cigarettes (ECs) are handheld electronic vaping devices which produce an aerosol formed by heating an e-liquid. Some people who smoke use ECs to stop or reduce smoking, but 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 and if they are safe to use for this purpose. This is an 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 May 2021, and reference-checked and contacted study authors. We screened abstracts from the Society for Research on Nicotine and Tobacco (SRNT) 2021 Annual Meeting. 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 61 completed studies, representing 16,759 participants, of which 34 were RCTs. Five of the 61 included studies were new to this review update. Of the included studies, we rated seven (all contributing to our main comparisons) at low risk of bias overall, 42 at high risk overall (including all 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) 1.53, 95% confidence interval (CI) 1.21 to 1.93; I(2) = 0%; 4 studies, 1924 participants). In absolute terms, this might translate to an additional three quitters per 100 (95% CI 1 to 6). There was low-certainty evidence (limited by very serious imprecision) that the rate of occurrence of AEs was similar (RR 0.98, 95% CI 0.80 to 1.19; I(2) = 0%; 2 studies, 485 participants). SAEs were rare, but there was insufficient evidence to determine whether rates differed between groups due to very serious imprecision (RR 1.30, 95% CI 0.89 to 1.90: I(2) = 0; 4 studies, 1424 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 1.94, 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%; 3 studies, 601 participants). There was insufficient evidence to determine whether rates of SAEs differed between groups, due to very serious imprecision (RR 1.06, 95% CI 0.47 to 2.38; I(2) = 0; 5 studies, 792 participants). Compared to behavioural support only/no support, quit rates were higher for participants randomized to nicotine EC (RR 2.61, 95% CI 1.44 to 4.74; I(2) = 0%; 6 studies, 2886 participants). In absolute terms this represents an additional six quitters per 100 (95% CI 2 to 15). 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 1.51, 95% CI 0.70 to 3.24; I(2) = 0%; 7 studies, 1303 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 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 moderate-certainty evidence that ECs with nicotine increase quit rates compared to NRT and 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. Overall incidence of SAEs was low across all study arms. We did not detect evidence of 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 now 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) 2021 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 - McRobbie, Hayden AU - McRobbie H AD - National Drug and Alcohol Research Centre, University of New South Wales, Sydney, Australia. FAU - Butler, Ailsa R AU - Butler AR 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 - 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 - 29845/CRUK_/Cancer Research UK/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PT - Systematic Review DEP - 20210914 PL - England TA - Cochrane Database Syst Rev JT - The Cochrane database of systematic reviews JID - 100909747 RN - 0 (Nicotinic Agonists) SB - IM UOF - Cochrane Database Syst Rev. 2021 Apr 29;4:CD010216. PMID: 33913154 UIN - Cochrane Database Syst Rev. 2022 Nov 17;11:CD010216. PMID: 36384212 CIN - Dtsch Arztebl Int. 2023 Jan 27;120(4):58. PMID: 36949642 MH - *Electronic Nicotine Delivery Systems MH - Humans MH - Nicotinic Agonists MH - *Smoking Cessation MH - Systematic Reviews as Topic MH - Tobacco Use Cessation Devices PMC - PMC8438601 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 received honoraria for speaking at smoking cessation educational events and sitting on an advisory board organized by Pfizer. 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. Dr. Rigotti was an 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, Dr. Rigotti has received honoraria from Achieve Life Sciences for consulting about cytisine. 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 has received travel reimbursement (but no honoraria) from Pfizer for attending advisory boards regarding varenicline. 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- 2021/09/15 06:00 MHDA- 2021/11/25 06:00 PMCR- 2022/09/14 CRDT- 2021/09/14 08:47 PHST- 2021/09/14 08:47 [entrez] PHST- 2021/09/15 06:00 [pubmed] PHST- 2021/11/25 06:00 [medline] PHST- 2022/09/14 00:00 [pmc-release] AID - CD010216.pub6 [pii] AID - 10.1002/14651858.CD010216.pub6 [doi] PST - epublish SO - Cochrane Database Syst Rev. 2021 Sep 14;9(9):CD010216. doi: 10.1002/14651858.CD010216.pub6.