Varenicline for smoking cessation in individuals who smoke cigarettes and use electronic cigarettes: a double-blind, randomised, placebo-controlled phase 3 trial

Resumo

Background The efficacy and safety of varenicline for smoking cessation among individuals who smoke tobacco cigarettes and also use electronic cigarettes (known e-cigarettes or vapes) have not been studied. We aimed to address this knowledge gap and examine predictors for smoking abstinence. Methods In this double-blind, placebo-controlled, single-centre randomised trial in Italy, we enrolled adults who used an e-cigarette daily for at least 12 months and who also smoked at least one tobacco cigarette per day and willingness to quit smoking. 155 participants were randomly assigned to receive either varenicline (n = 78) matched placebo (n = 77). Varenicline (1 mg, administered twice daily for 12 weeks) was given in combination with smoking cessation counseling in dual users with an intention to quit smoking. Participants in treatment groups received the same smoking cessation counselling throughout the whole duration of the study. The trial consisted of a 12-week treatment phase followed by a 12-week follow-up. The primary efficacy endpoint was continuous abstinence rate (CAR) in weeks 4-12. Secondary efficacy endpoints were the CAR in weeks and 7-day point prevalence of smoking abstinence at weeks 12 and 24. This study is registered in EUDRACT, 2016-000339-42. Findings Between November 2018, and February 2020, 114 participants (61 in the varenicline group and 53 placebo group) completed the intervention phase at week 12 and 88 participants (52 in the varenicline group and the placebo group) completed the follow-up phase at week 24. CARs were significantly higher for the varenicline placebo at each time-point: 50.0% vs 16.9% (OR = 4.9; 95% CI, 2.3-10.4; P < 0.0001) between weeks 4 and 12; 48.7% vs 14.3% (OR = 5.7; 95% CI, 2.6-12.3; P < 0.0001) between weeks 4 and 24. The 7-day point prevalence smoking abstinence was also higher for the varenicline than placebo at each time point. Adverse events rated as mild or moderate and rarely led to treatment discontinuation. Interpretation Our findings indicate that inclusion of varenicline in a cessation programme for adults who smoke use e-cigarettes with an intention to quit smoking could result in smoking abstinence without serious adverse events. In the absence of evidence from other smoking cessation methods, it could be useful to suggest the use of varenicline in cessation programmes specifically designed to help dual users stop smoking. Further research in larger and generalisable populations is required to strengthen such a suggestion.