Smoking cessation medicines and e-cigarettes: a systematic review, network meta-analysis and cost-effectiveness analysis

Abstract

Background Cigarette smoking is one of the leading causes of early death. Varenicline [Champix (UK), Pfizer Europe MA EEIG, Brussels, Belgium; or Chantix (USA), Pfizer Inc., Mission, KS, USA], bupropion (Zyban; GlaxoSmithKline, Brentford, UK) and nicotine replacement therapy are licensed aids for quitting smoking in the UK. Although not licensed, e-cigarettes may also be used in English smoking cessation services. Concerns have been raised about the safety of these medicines and e-cigarettes. Objectives To determine the clinical effectiveness, safety and cost-effectiveness of smoking cessation medicines and e-cigarettes. Design Systematic reviews, network meta-analyses and cost-effectiveness analysis informed by the network meta-analysis results. Setting Primary care practices, hospitals, clinics, universities, workplaces, nursing or residential homes. Participants Smokers aged ≥ 18 years of all ethnicities using UK-licensed smoking cessation therapies and/or e-cigarettes. Interventions Varenicline, bupropion and nicotine replacement therapy as monotherapies and in combination treatments at standard, low or high dose, combination nicotine replacement therapy and e-cigarette monotherapies. Main outcome measures Effectiveness – continuous or sustained abstinence. Safety – serious adverse events, major adverse cardiovascular events and major adverse neuropsychiatric events. Data sources Ten databases, reference lists of relevant research articles and previous reviews. Searches were performed from inception until 16 March 2017 and updated on 19 February 2019. Review methods Three reviewers screened the search results. Data were extracted and risk of bias was assessed by one reviewer and checked by the other reviewers. Network meta-analyses were conducted for effectiveness and safety outcomes. Cost-effectiveness was evaluated using an amended version of the Benefits of Smoking Cessation on Outcomes model. Results Most monotherapies and combination treatments were more effective than placebo at achieving sustained abstinence. Varenicline standard plus nicotine replacement therapy standard (odds ratio 5.75, 95% credible interval 2.27 to 14.90) was ranked first for sustained abstinence, followed by e-cigarette low (odds ratio 3.22, 95% credible interval 0.97 to 12.60), although these estimates have high uncertainty. We found effect modification for counselling and dependence, with a higher proportion of smokers who received counselling achieving sustained abstinence than those who did not receive counselling, and higher odds of sustained abstinence among participants with higher average dependence scores. We found that bupropion standard increased odds of serious adverse events compared with placebo (odds ratio 1.27, 95% credible interval 1.04 to 1.58). There were no differences between interventions in terms of major adverse cardiovascular events. There was evidence of increased odds of major adverse neuropsychiatric events for smokers randomised to varenicline standard compared with those randomised to bupropion standard (odds ratio 1.43, 95% credible interval 1.02 to 2.09). There was a high level of uncertainty about the most cost-effective intervention, although all were cost-effective compared with nicotine replacement therapy low at the £20,000 per quality-adjusted life-year threshold. E-cigarette low appeared to be most cost-effective in the base case, followed by varenicline standard plus nicotine replacement therapy standard. When the impact of major adverse neuropsychiatric events was excluded, varenicline standard plus nicotine replacement therapy standard was most cost-effective, followed by varenicline low plus nicotine replacement therapy standard. When limited to licensed interventions in the UK, nicotine replacement therapy standard was most cost-effective, followed by varenicline standard. Limitations Comparisons between active interventions were informed almost exclusively by indirect evidence. Findings were imprecise because of the small numbers of adverse events identified. Conclusions Combined therapies of medicines are among the most clinically effective, safe and cost-effective treatment options for smokers. Although the combined therapy of nicotine replacement therapy and varenicline at standard doses was the most effective treatment, this is currently unlicensed for use in the UK. Future work Researchers should examine the use of these treatments alongside counselling and continue investigating the long-term effectiveness and safety of e-cigarettes for smoking cessation compared with active interventions such as nicotine replacement therapy. Study registration This study is registered as PROSPERO CRD42016041302. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 59. See the NIHR Journals Library website for further project information.

An update on vaping and nicotine prescribing

“…No trials have directly compared vaping with varenicline or bupropion; however, a recent network meta-analysis of 171 RCTs by the UK National Institute for Health Research concluded that electronic cigarettes were more effective for smoking cessation than either medication. 17 The findings from RCTs are consistent with observational and population studies and the accelerated decline in smoking rates in the US and UK after vaping became widely available. [18][19][20] The role of the general practitioner GPs can assess suitability for vaping, provide additional quitting support and can write a nicotine prescription if appropriate.…”

Comparative clinical effectiveness and safety of tobacco cessation pharmacotherapies and electronic cigarettes: a systematic review and network meta‐analysis of randomized controlled trials

“…shows that our finding that varenicline standard + NRT standard has the highest estimated odds ratio (OR = 5.75, 95% CrI = 2.27-14.88) is robust, but sensitive to the level of imprecision and potential biases in five studies (three rated high or unclear risk of bias), which could lead to either varenicline + bupropion standard , e-cigarette low or e-F I G U R E 3 Forest plot with results of the fixed class network meta-analysis (NMA) model for sustained abstinence (a), prolonged abstinence (b), any abstinence (c) and 7-day point prevalence abstinence (PPA) (d) cigarette high being ranked first for sustained abstinence. However, any possible biases in low/unclear risk of bias-rated studies would have to alter the OR by at least a factor of 1.6 to change the firstplace ranking.Prolonged, any abstinence and 7-day PPA Similar results to those for sustained abstinence were obtained for the other abstinence outcomes (Supporting information, Appendix, pp [29][30][31][32][33][34][35]…”

“…We used vague normal priors for all treatment effect parameters and uniform (0.5) priors for all standard deviation parameters. Full details are reported in Thomas et al [35] We also report the probability that each intervention class is ranked best, second best, and so on, across outcomes using rank-o-grams [33].…”

“…The inclusion of electronic cigarettes and specification of covariates were decided following the submission of our PROSPERO record and protocol manuscript for peer review. The findings of our analyses of safety data from observational studies with control groups [ 35 ] and our cost‐effectiveness analyses [ 36 ] are reported elsewhere. We were unable to include and analyse craving and withdrawal data, as these were rarely reported among the included studies and were measured using a variety of measures and scales, so evidence synthesis was impossible.…”

“…We felt that this decision would retain the most robust data and minimize bias and heterogeneity while keeping the project manageable. Trials that only collected self‐reported data are included in the study characteristics and risk of bias tables in the Supporting information Appendices of our Health Technology Assessment (HTA) report [ 35 ]. We had planned to analyse sustained abstinence data from multiple follow‐up times using survival synthesis methods for time to relapse.…”