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

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.

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

“…Absolute probability of 1-year continuous cessation based on NRT standard taken from Taylor et al158 and ORs estimated from the NMA (seeChapter 5) This table is reproduced with permission from Thomas et al67 This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: https://creativecommons.org/ licenses/by/4.0/.…”

“…Comparison of different NMA models for major adverse cardiovascular events (91 data points) SD d , standard deviation across treatment effect estimates; SD D , standard deviation across class effect estimates. This table has been adapted with permission from Thomas et al67 This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: https://creativecommons.org/licenses/by/4.0/.…”

Empfehlungen zum Umgang mit der elektronischen Zigarette (E-Zigarette)

“…Entwöhnungsmedikamenten sind gut untersucht, wirksam und sicher. Vareniclin ist den anderen Substanzen überlegen [47], aber zurzeit nicht verfügbar. Vergleichsuntersuchungen zwischen E-Zigaretten und Vareniclin liegen nicht vor [48].…”

Die E-Zigarette – Mittel zur Tabakentwöhnung?

“…In den RCT waren mit E-Zigaretten 8 von 100 Personen mehr abstinent als mit NET, während in den OS E-Zigaretten nicht überlegen waren. Eine weitere Studie [24] untersuchte den Effekt von gängigen suchthemmenden Medikamenten bei 363 RCT mit 201 045 Teilnehmern. Ein signifikanter anhaltender Entwöhnungseffekt gegenüber Placebo war in unterschiedlichen Dosierungen und Kombinationen nachweisbar für NET (OR 2,01 bis 2,23), Bupoprion (OR 1,73 bis 1,75), Vareniclin (1,79 bis 2,83), Vareniclin plus NET (OR 2,34 bis 5,70) und E-Zigaretten (OR 3,22).…”

“…Ein signifikanter anhaltender Entwöhnungseffekt gegenüber Placebo war in unterschiedlichen Dosierungen und Kombinationen nachweisbar für NET (OR 2,01 bis 2,23), Bupoprion (OR 1,73 bis 1,75), Vareniclin (1,79 bis 2,83), Vareniclin plus NET (OR 2,34 bis 5,70) und E-Zigaretten (OR 3,22). Eine Überlegenheit von E-Zigaretten gegenüber Placebo oder NET wurde als "very imprecise evidence" bewertet [24]. Somit ist eine Überlegenheit der E-Zigarette gegenüber der in der S-3-Leitlinie empfohlenen Therapie mit der Kombination aus verhaltenstherapeutischer Intervention und NET, Bupropion, Vareniclin oder Cytisin bisher nicht sicher zu belegen.…”