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. 2022 Apr;117(4):861-876.
doi: 10.1111/add.15675. Epub 2021 Oct 11.

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

Affiliations

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

Kyla H Thomas et al. Addiction. 2022 Apr.

Abstract

Aim: To determine how varenicline, bupropion, nicotine replacement therapy (NRT) and electronic cigarettes compare with respect to their clinical effectiveness and safety.

Method: Systematic reviews and Bayesian network meta-analyses of randomized controlled trials, in any setting, of varenicline, bupropion, NRT and e-cigarettes (in high, standard and low doses, alone or in combination) in adult smokers and smokeless tobacco users with follow-up duration of 24 weeks or greater (effectiveness) or any duration (safety). Nine databases were searched until 19 February 2019. Primary outcomes were sustained tobacco abstinence and serious adverse events (SAEs). We estimated odds ratios (ORs) and treatment rankings and conducted meta-regression to explore covariates.

Results: We identified 363 trials for effectiveness and 355 for safety. Most monotherapies and combination therapies were more effective than placebo at helping participants to achieve sustained abstinence; the most effective of these, estimated with some imprecision, were varenicline standard [OR = 2.83, 95% credible interval (CrI) = 2.34-3.39] and varenicline standard + NRT standard (OR = 5.75, 95% CrI = 2.27-14.88). Estimates were higher in smokers receiving counselling than in those without and in studies with higher baseline nicotine dependence scores than in those with lower scores. Varenicline standard + NRT standard showed a high probability of being ranked best or second-best. For safety, only bupropion at standard dose increased the odds of experiencing SAEs compared with placebo (OR = 1.27, 95% CrI = 1.04-1.58), and we found no evidence of effect modification.

Conclusions: Most tobacco cessation monotherapies and combination therapies are more effective than placebo at helping participants to achieve sustained abstinence, with varenicline appearing to be most effective based on current evidence. There does not appear to be strong evidence of associations between most tobacco cessation pharmacotherapies and adverse events; however, the data are limited and there is a need for improved reporting of safety data.

Keywords: adverse events; bupropion; effectiveness; electronic cigarettes; network meta-analysis; nicotine replacement therapy; safety; smoking; varenicline.

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Figures

FIGURE 1
FIGURE 1
Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) flow diagram for effectiveness study records
FIGURE 2
FIGURE 2
Network meta‐analysis of eligible comparisons for sustained abstinence (a), prolonged abstinence (b), any abstinence (c) and 7‐day point prevalence abstinence (PPA) (d). Thicker edges in network figures represent comparisons with a higher number of randomized patients, while interventions with a larger number of randomized patients have larger circles. Interventions were excluded if they were disconnected from the main network
FIGURE 3
FIGURE 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)
FIGURE 4
FIGURE 4
Rank‐o‐gram of intervention classes (at standard doses with the exception of e‐cigarettes) across effectiveness outcomes. All nine intervention classes contributed to the ranking for any abstinence, whereas eight intervention classes were included for sustained abstinence [bupropion standard + nicotine replacement therapy (NRT) had no data], six for 7‐day point prevalence abstinence (PPA) (e‐cigarette low, e‐cigarette high and bupropion standard + NRT standard had no data) and four for prolonged abstinence (no data for NRT standard, e‐cigarette low, e‐cigarette high, bupropion standard + NRT standard, varenicline standard + NRT standard)
FIGURE 5
FIGURE 5
Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) flow diagram for safety study records
FIGURE 6
FIGURE 6
Network meta‐analysis of eligible comparisons for serious adverse events (a), major adverse cardiovascular events (b) and major adverse neuropsychiatric events (c). Thicker edges in network figures represent comparisons with a higher number of randomized patients, while interventions with a larger number of randomized patients have larger circles
FIGURE 7
FIGURE 7
Forest plot with results of the fixed‐class network meta‐analysis (NMA) model for serious adverse events (a), major adverse cardiovascular events (b) and major adverse neuropsychiatric events (c)
FIGURE 8
FIGURE 8
Rank‐o‐gram of interventions across safety outcomes. Eight intervention classes contributed to the ranking for serious adverse events [bupropion standard + nicotine standard replacement therapy (NRT) had no data], whereas six intervention classes were included for major adverse neuropsychiatric events (e‐cigarette low, e‐cigarette high and bupropion standard + NRT standard had no data) and seven for major adverse cardiovascular events (e‐cigarette low and varenicline standard + NRT standard had no data)

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