PMID- 38189560 OWN - NLM STAT- MEDLINE DCOM- 20240109 LR - 20240404 IS - 1469-493X (Electronic) IS - 1361-6137 (Linking) VI - 1 IP - 1 DP - 2024 Jan 8 TI - Electronic cigarettes for smoking cessation. PG - CD010216 LID - 10.1002/14651858.CD010216.pub8 [doi] LID - CD010216 AB - BACKGROUND: Electronic cigarettes (ECs) are handheld electronic vaping devices which produce an aerosol by heating an e-liquid. 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 safety, tolerability and effectiveness of using electronic cigarettes (ECs) to help people who smoke tobacco achieve long-term smoking abstinence, in comparison to non-nicotine EC, other smoking cessation treatments and no treatment. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group's Specialized Register to 1 February 2023, and Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and PsycINFO to 1 July 2023, and reference-checked and contacted study authors. SELECTION CRITERIA: We included 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 as these studies have the potential to provide further information on harms and longer-term use. Studies had to report an eligible outcome. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods for screening and data extraction. Critical outcomes were abstinence from smoking after at least six months, adverse events (AEs), and serious adverse events (SAEs). 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 pairwise and network meta-analyses (NMA). MAIN RESULTS: We included 88 completed studies (10 new to this update), representing 27,235 participants, of which 47 were randomized controlled trials (RCTs). Of the included studies, we rated ten (all but one contributing to our main comparisons) at low risk of bias overall, 58 at high risk overall (including all non-randomized studies), and the remainder at unclear risk. There is high certainty that nicotine EC increases quit rates compared to nicotine replacement therapy (NRT) (RR 1.59, 95% CI 1.29 to 1.93; I(2) = 0%; 7 studies, 2544 participants). In absolute terms, this might translate to an additional four quitters per 100 (95% CI 2 to 6 more). There is moderate-certainty evidence (limited by imprecision) that the rate of occurrence of AEs is similar between groups (RR 1.03, 95% CI 0.91 to 1.17; I(2) = 0%; 5 studies, 2052 participants). SAEs were rare, and there is insufficient evidence to determine whether rates differ between groups due to very serious imprecision (RR 1.20, 95% CI 0.90 to 1.60; I(2) = 32%; 6 studies, 2761 participants; low-certainty evidence). There is moderate-certainty evidence, limited by imprecision, that nicotine EC increases quit rates compared to non-nicotine EC (RR 1.46, 95% CI 1.09 to 1.96; I(2) = 4%; 6 studies, 1613 participants). In absolute terms, this might lead to an additional three quitters per 100 (95% CI 1 to 7 more). There is 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 is insufficient evidence to determine whether rates of SAEs differ between groups, due to very serious imprecision (RR 1.00, 95% CI 0.56 to 1.79; I(2) = 0%; 9 studies, 1412 participants; low-certainty evidence). Due to issues with risk of bias, there is low-certainty evidence that, compared to behavioural support only/no support, quit rates may be higher for participants randomized to nicotine EC (RR 1.88, 95% CI 1.56 to 2.25; I(2) = 0%; 9 studies, 5024 participants). In absolute terms, this represents an additional four quitters per 100 (95% CI 2 to 5 more). There was some evidence that (non-serious) AEs may be more common in people randomized to nicotine EC (RR 1.22, 95% CI 1.12 to 1.32; I(2) = 41%, low-certainty evidence; 4 studies, 765 participants) and, again, insufficient evidence to determine whether rates of SAEs differed between groups (RR 0.89, 95% CI 0.59 to 1.34; I(2) = 23%; 10 studies, 3263 participants; very low-certainty evidence). Results from the NMA were consistent with those from pairwise meta-analyses for all critical outcomes, and there was no indication of inconsistency within the networks. 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 both 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 due to risk of bias inherent in the study design. 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 the 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. 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) 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 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 - 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. 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 - Livingstone-Banks, Jonathan AU - Livingstone-Banks J AD - Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK. FAU - Morris, Tom AU - Morris T AD - Department of Population Health Sciences, University of Leicester, Leicester, UK. FAU - Hartmann-Boyce, Jamie AU - Hartmann-Boyce J AD - Department of Health Promotion and Policy, University of Massachusetts, Amherst, MA, USA. LA - eng GR - PRCPJT-NOV22/100012/CRUK_/Cancer Research UK/United Kingdom PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20240108 PL - England TA - Cochrane Database Syst Rev JT - The Cochrane database of systematic reviews JID - 100909747 RN - 6M3C89ZY6R (Nicotine) SB - IM UOF - Cochrane Database Syst Rev. 2022 Nov 17;11:CD010216. PMID: 36384212 MH - Humans MH - *Electronic Nicotine Delivery Systems MH - Nicotine/adverse effects MH - Nicotine Replacement Therapy MH - Randomized Controlled Trials as Topic MH - *Smoking Cessation MH - Network Meta-Analysis PMC - PMC10772980 COIS- RB holds a National Institiute for Health Research (NIHR) grant, but this did not directly fund this current work. RB is also supported by Cancer Research UK. 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 reports research grants from the Health Research Council of NZ, the Heart Foundation of NZ and the NZ Ministry of Health (Monitoring the Illicit Tobacco Trade in NZ), the NZ Ministry of Foreign Affairs and Trade (estimating the numbers of tobacco and vaping retailers in NZ) and Auckland Council (Evaluation of the Smokefree Auckland Project). CB reports research grants from: Wellcome Trust UK, REFLECT Cool roofing trial; Health Research Council of NZ, Cess@tion trial, FASD studies; The University of Auckland Transdisciplinary Ideation Fund for The Collective website; Putahi Manawa Centre for Research Excellence in Heart Health Integrated Research Module grant; US NIH (via Wake Forest University): CENIC study; Education NZ Smoking cessation in China; Marsden Fund (NZ): Respiratory effects of vaping. He has recently led a project funded by Pfizer (NZ) on chronic disease management. CB is President of the Society for Research on Nicotine & Tobacco; Member of the Expert Working Group on Tobacco, Health Coalition Aotearoa; Member of the Scientific Advisory Committee of the Cancer Society of NZ; Member of the Scientific Advisory Committee of the RESPIRE research programme, University of Edinburgh; Member of the CREATE Tobacco Endgame Centre of Research Excellence, Australia. CB has carried out independent contractor consultancy for Johnson and Johnson in 2020 on NRT and to Kervue Inc. regarding setting up an ASEAN regional smoking cessation networking board. ARB's work on this review has been supported by Cancer Research UK Project Award funding. This is not deemed a conflict of interest. PH was principal investigator on three of the trials included in this review two funded by NIHR and one by CRUK 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. JHB been an applicant and pricipal investigator on project grants to carry out research in the area of tobacco control from National Institute for Health Research and Cancer Research UK. None of these are deemed conflicts of interest. NL has received payment for lectures on systematic review methodology (Oxford University Hospitals NHS Foundation Trust), and has been an applicant and pricipal investigator on project funding to carry out research in the area of tobacco control from the NIHR Evidence Synthesis programme, Cancer Research UK (charity), Clarion Futures (charity), Oxfordshire County Council and the NIHR Oxfordshire and Thames Valley ARC, and Greater Manchester NHS Integrated Care. None of this is deemed a conflict of interest. JLB was employed by the University of Oxford to work as a Managing Editor and Information Specialist for the Cochrane Tobacco Addiction Review Group before becoming an author on this review. During this time, he was involved in the editorial processing of the review. He is now an Editor for Cochrane. Since becoming an author, he has not been involved in the editorial process for this review. Core infrastructure funding for the Cochrane Tobacco Addiction Group was provided by the NIHR to the University of Oxford. HM is an employee of Te Whatu Ora-Health New Zealand. HM holds fellowships with New Zealand College of Public Health Medicine (NZCPHM represents public health medicine specialists); and the Society of Lifestyle Medicine. HM is a Professor in Public Health Interventions, University of New South Wales, National Drug and Alcohol Research Centre and provide mentorship and advice for the Tobacco Research Group. He is currently a named investigator on three smoking cessation trials that are all funded by the Australian National Health and Medical Research Council (NHMRC). HM is a named investigator of a smoking cessation trial at Queen Mary University of London, funded by the National Institute of Health Research. HM is a named investigator of a study that examines an approach to prevent e-cigarette use among adolescents at University of Sydney, funded by the Australian National Health and Medical Research Council (NHMRC). HM is a co-investigator on a number of studies included in this review. HM is a board Member, Rotorua Community Youth Centre Trust. CN has received an honorarium from Vox Media for filming a 'nicotine explainer' on the role of nicotine in addiction. This is not deemed a conflict of interest. CN is a member of the advisory council for 'Action on Smoking and Health (ASH)'. CN is co-PI on an ongoing trial (protocol) Cessation of Smoking Trial in the Emergency Department (CoSTED) - National Institute for Health Research - Health Technology Assessment. NIHR129438. TM is funded by the National Institute for Health Research (NIHR) Complex Reviews Support Unit (CRSU) and supported by the NIHR Applied Research Collaboration East Midlands (ARC EM) and Leicester Biomedical Research Centre (BRC). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. 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. NAR is employed by Massachusetts General Hospital (MGH). 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 Nuffield Department of Primary Care Health Sciences at the University of Oxford. This is not deemed a conflict of interest TT has no known conflicts of interest. EDAT- 2024/01/08 12:43 MHDA- 2024/01/09 06:42 PMCR- 2025/01/08 CRDT- 2024/01/08 09:56 PHST- 2025/01/08 00:00 [pmc-release] PHST- 2024/01/09 06:42 [medline] PHST- 2024/01/08 12:43 [pubmed] PHST- 2024/01/08 09:56 [entrez] AID - CD010216.pub8 [pii] AID - 10.1002/14651858.CD010216.pub8 [doi] PST - epublish SO - Cochrane Database Syst Rev. 2024 Jan 8;1(1):CD010216. doi: 10.1002/14651858.CD010216.pub8.