PMID- 37335995 OWN - NLM STAT- MEDLINE DCOM- 20230621 LR - 20231119 IS - 1469-493X (Electronic) IS - 1361-6137 (Linking) VI - 6 IP - 6 DP - 2023 Jun 19 TI - Different doses, durations and modes of delivery of nicotine replacement therapy for smoking cessation. PG - CD013308 LID - 10.1002/14651858.CD013308.pub2 [doi] LID - CD013308 AB - BACKGROUND: Nicotine replacement therapy (NRT) aims to replace nicotine from cigarettes. This helps to reduce cravings and withdrawal symptoms, and ease the transition from cigarette smoking to complete abstinence. Although there is high-certainty evidence that NRT is effective for achieving long-term smoking abstinence, it is unclear whether different forms, doses, durations of treatment or timing of use impacts its effects. OBJECTIVES: To determine the effectiveness and safety of different forms, deliveries, doses, durations and schedules of NRT, for achieving long-term smoking cessation. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group trials register for papers mentioning NRT in the title, abstract or keywords, most recently in April 2022. SELECTION CRITERIA: We included randomised trials in people motivated to quit, comparing one type of NRT use with another. We excluded studies that did not assess cessation as an outcome, with follow-up of fewer than six months, and with additional intervention components not matched between arms. Separate reviews cover studies comparing NRT to control, or to other pharmacotherapies. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methods. We measured smoking abstinence after at least six months, using the most rigorous definition available. We extracted data on cardiac adverse events (AEs), serious adverse events (SAEs) and study withdrawals due to treatment. MAIN RESULTS: We identified 68 completed studies with 43,327 participants, five of which are new to this update. Most completed studies recruited adults either from the community or from healthcare clinics. We judged 28 of the 68 studies to be at high risk of bias. Restricting the analysis only to those studies at low or unclear risk of bias did not significantly alter results for any comparisons apart from the preloading comparison, which tested the effect of using NRT prior to quit day whilst still smoking. There is high-certainty evidence that combination NRT (fast-acting form plus patch) results in higher long-term quit rates than single form (risk ratio (RR) 1.27, 95% confidence interval (CI) 1.17 to 1.37; I(2) = 12%; 16 studies, 12,169 participants). Moderate-certainty evidence, limited by imprecision, indicates that 42/44 mg patches are as effective as 21/22 mg (24-hour) patches (RR 1.09, 95% CI 0.93 to 1.29; I(2) = 38%; 5 studies, 1655 participants), and that 21 mg patches are more effective than 14 mg (24-hour) patches (RR 1.48, 95% CI 1.06 to 2.08; 1 study, 537 participants). Moderate-certainty evidence, again limited by imprecision, also suggests a benefit of 25 mg over 15 mg (16-hour) patches, but the lower limit of the CI encompassed no difference (RR 1.19, 95% CI 1.00 to 1.41; I(2) = 0%; 3 studies, 3446 participants). Nine studies tested the effect of using NRT prior to quit day (preloading) in comparison to using it from quit day onward. There was moderate-certainty evidence, limited by risk of bias, of a favourable effect of preloading on abstinence (RR 1.25, 95% CI 1.08 to 1.44; I(2) = 0%; 9 studies, 4395 participants). High-certainty evidence from eight studies suggests that using either a form of fast-acting NRT or a nicotine patch results in similar long-term quit rates (RR 0.90, 95% CI 0.77 to 1.05; I(2) = 0%; 8 studies, 3319 participants). We found no clear evidence of an effect of duration of nicotine patch use (low-certainty evidence); duration of combination NRT use (low- and very low-certainty evidence); or fast-acting NRT type (very low-certainty evidence). Cardiac AEs, SAEs and withdrawals due to treatment were all measured variably and infrequently across studies, resulting in low- or very low-certainty evidence for all comparisons. Most comparisons found no clear evidence of an effect on these outcomes, and rates were low overall. More withdrawals due to treatment were reported in people using nasal spray compared to patches in one study (RR 3.47, 95% CI 1.15 to 10.46; 1 study, 922 participants; very low-certainty evidence) and in people using 42/44 mg patches in comparison to 21/22 mg patches across two studies (RR 4.99, 95% CI 1.60 to 15.50; I(2) = 0%; 2 studies, 544 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: There is high-certainty evidence that using combination NRT versus single-form NRT and 4 mg versus 2 mg nicotine gum can result in an increase in the chances of successfully stopping smoking. Due to imprecision, evidence was of moderate certainty for patch dose comparisons. There is some indication that the lower-dose nicotine patches and gum may be less effective than higher-dose products. Using a fast-acting form of NRT, such as gum or lozenge, resulted in similar quit rates to nicotine patches. There is moderate-certainty evidence that using NRT before quitting may improve quit rates versus using it from quit date only; however, further research is needed to ensure the robustness of this finding. Evidence for the comparative safety and tolerability of different types of NRT use is limited. New studies should ensure that AEs, SAEs and withdrawals due to treatment are reported. CI - Copyright (c) 2023 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration. FAU - Theodoulou, Annika AU - Theodoulou A AD - Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK. FAU - Chepkin, Samantha C AU - Chepkin SC AD - NHS Hertfordshire and West Essex Integrated Care Board, Welwyn Garden City, UK. FAU - Ye, Weiyu AU - Ye W AD - Oxford University Clinical Academic Graduate School, University of Oxford, Oxford, UK. FAU - Fanshawe, Thomas R AU - Fanshawe TR 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 - Hartmann-Boyce, Jamie AU - Hartmann-Boyce J AD - Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK. FAU - Livingstone-Banks, Jonathan AU - Livingstone-Banks J AD - Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK. FAU - Hajizadeh, Anisa AU - Hajizadeh A 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. LA - eng SI - ClinicalTrials.gov/NCT01889771 SI - ClinicalTrials.gov/NCT00086385 SI - ClinicalTrials.gov/NCT01807871 SI - ClinicalTrials.gov/NCT01622998 SI - ClinicalTrials.gov/NCT03836560 SI - ClinicalTrials.gov/NCT00332644 SI - ClinicalTrials.gov/NCT00861276 SI - ClinicalTrials.gov/NCT01120704 SI - ClinicalTrials.gov/00364156 SI - ClinicalTrials.gov/00365508 SI - ClinicalTrials.gov/NCT01047527 SI - ClinicalTrials.gov/NCT01623505 SI - ClinicalTrials.gov/NCT01122238 SI - ClinicalTrials.gov/NCT00984724 SI - ClinicalTrials.gov/NCT00046813 SI - ClinicalTrials.gov/NCT04188873 SI - ClinicalTrials.gov/NCT03000387 PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PT - Systematic Review DEP - 20230619 PL - England TA - Cochrane Database Syst Rev JT - The Cochrane database of systematic reviews JID - 100909747 RN - 6M3C89ZY6R (Nicotine) RN - 0 (Nicotinic Agonists) SB - IM UOF - Cochrane Database Syst Rev. 2019 Apr 18;4:CD013308. PMID: 30997928 MH - Humans MH - *Smoking Cessation/methods MH - Nicotine MH - Nicotinic Agonists/adverse effects MH - Tobacco Use Cessation Devices MH - Delivery of Health Care PMC - PMC10278922 COIS- AT: none known. SCC: no relevant interests; Consultant in Healthcare Public Health & Associate Medical Director for Planned Care & Prioritisation, NHS Hertfordshire and West Essex Integrated Care Board (previously at NHS East and North Hertfordshire Clinical Commissioning Group); Member of British Medical Association; Member of Faculty of Public Health; Cochrane Clinical Answers Associate Editor and authored two Cochrane Clinical Answers relating to smoking cessation. WY: none known. TRF: none known. CB: Johnson and Johnson (Consultant); Society for Research on Nicotine and Tobacco (Fiduciary Officer); published papers expressing a view on the interventions in the work as follows: Jackson S, Bullen C. (2022) UK report underscores potential of e-cigarettes to reduce smoking harms. Lancet doi.org/10.1016/S0140-6736(22)01997-3; Public Health Medicine Specialist, University of Auckland, Smoking cessation clinic for staff and students. involved in Study 1: ASCEND Trial funded by NZ Health Research Council Study 2: ASCEND 2 Trial funded by NZ Health Research Council (ASCEND Trial, University of Auckland, PI: BULLEN (Bullen 2010); ASCEND 2 Trial, University of Auckland, PI WALKER (Walker 2011)). CB did not extract the data or conduct risk of bias assessment for these trials. JHB: no relevant interests; has published on this topic and been interviewed by media outlets about it; Editor for Cochrane Tobacco Addiction Review Group but not involved in the editorial process for this review update. JLB: no relevant interests; Managing Editor of the Cochrane Tobacco Addiction Group but not involved in the editorial process for this review update. AH: none known. NL: Cancer Research UK (Grant / Contract); National Institute for Health Research( Grant / Contract); Oxford University Hospitals NHS Foundation Trust (Employment); wrote pieces for The Conversation on the findings of Cochrane Reviews assessing the effects of treatments for smoking cessation; received funding from CRUK and the NIHR (a part of the NHS) who both have interests in people stopping smoking and run educational campaigns and in the latter case provide treatment to encourage people to stop smoking; Managing Editor of the Cochrane Tobacco Addiction and funded by the NIHR to carry out this role but not involved in the editorial process for this review update.; involved in Preloading Investigators 2018, a randomised controlled trial sponsored by the University of Birmingham in the first instance and then the University of Oxford. NL did not extract data or carry out a risk of bias assessment for this study, as advised by Cochrane. EDAT- 2023/06/19 19:11 MHDA- 2023/06/21 06:42 PMCR- 2023/06/19 CRDT- 2023/06/19 17:12 PHST- 2023/06/21 06:42 [medline] PHST- 2023/06/19 19:11 [pubmed] PHST- 2023/06/19 17:12 [entrez] PHST- 2023/06/19 00:00 [pmc-release] AID - CD013308.pub2 [pii] AID - 10.1002/14651858.CD013308.pub2 [doi] PST - epublish SO - Cochrane Database Syst Rev. 2023 Jun 19;6(6):CD013308. doi: 10.1002/14651858.CD013308.pub2.