http://orcid.org/0000-0003-0432-2624
To, The Editor
In the SAVE trial, the authors have tried to address the lacuna of previous trials related to smoking cessation in acute exacerbation of COPD (Citation1). They have evaluated current smokers, admitted with COPD exacerbation, when they are most vulnerable and compared smoking cessation with varenicline combined with an intensive counselling versus intensive counselling alone. The trial failed to demonstrate any long-term benefit in continuous abstinence rate (CAR) at 1 year in the varenicline group compared to controls (Citation1), which is in contrast to previous trials where although there was a decline in abstinence rate from 12 weeks to 1 years, but the difference from placebo was still maintained (Citation2). A possible reason mentioned by the authors is the small sample size due to exclusion of all patients with psychiatric disorders, and premature cessation of funding. However, there are many other points to ponder and evaluate in the trial.
The authors mention that in case of drug intolerance, dose of varenicline would be reduced to 1 mg per day; however, the number of subjects requiring such a reduction has not been mentioned. It is possible that abstinence rate was lower in these patients and hence a subgroup analysis may provide a possible reason for low CAR at 52 weeks.
Sleep disordered events were found more frequently in the varenicline group although whether, the difference was significant or not, is not mentioned. Also, if the adverse events were classified as those occurring within 12 weeks (during the drug treatment period) or beyond, it could give a better association of drug with adverse events.
An interesting observation was that while there was no significant difference between the two groups in other forms of nicotine consumption at 12 weeks, significantly more patients took up other forms of nicotine by the end of first year in the placebo arm. This is in contrast to a meta-analysis of trials on effect of varenicline on smokeless tobacco, wherein difference was seen at 12 weeks but not at 26 weeks (Citation3). The reasons for this need to be evaluated. Is it possible that counselling is directed mainly against smoking and leaves patients vulnerable to other forms of tobacco?
The response rate in placebo group was much higher than seen in previous trial with stable COPD patients (CAR 27% vs 8% and 25% vs 5% at 12 weeks and 52 weeks respectively) (Citation2) but in line with previous study on in-patients (Citation4). Recent acute exacerbation could have been a major contributory factor. Thus, every admission is probably a precious opportunity to initiate intensive counselling for smoking cessation.
Furthermore, previous trials with varenicline used for 24 weeks (Citation5) and 52 weeks (Citation6) have shown sustained benefit, hence the fall in abstinence in the study group of SAVE trial could be evaluated with re-challenge or prolonged duration of therapy and a sub-group analysis in future studies.
This trial is a laudable effort to evaluate the role of early varenicline in COPD, however, further large-scale trials are needed to define the duration and timing of initiation of varenicline in these patients.
Declaration of interest
All the authors have nothing to disclose. The coi form being submitted separately need not be mentioned in the article file to be published.
References
- Le Mao R, Tromeur C, Paleiron N, et al. Effect of early initiation of varenicline on smoking cessation in COPD patients admitted for exacerbation: the save randomized clinical trial. COPD 2020;17(1):7–14.
- Tashkin DP, Rennard S, Hays JT, et al. Effects of varenicline on smoking cessation in patients with mild to moderate COPD: a randomized controlled trial. Chest. 2011;139(3):591–599.
- Schwartz J, Fadahunsi O, Hingorani R, et al. Use of varenicline in smokeless tobacco cessation: a systematic review and meta-analysis. Nicotine Tob Res. 2016;18(1):10–16. doi:10.1093/ntr/ntv010.
- Smith BJ, Carson KV, Brinn MP, et al. Smoking Termination Opportunity for in Patients (STOP): superiority of a course of varenicline tartrate plus counselling over counselling alone for smoking cessation: a 12-month randomised controlled trial for inpatients. Thorax 2013;68(5):485–486. doi:10.1136/thoraxjnl-2012-202484.
- Hajek P, Tonnesen P, Arteaga C, et al. Varenicline in prevention of relapse to smoking: Effect of quit pattern on response to extended treatment. Addiction. 2009;104(9):1597–1602. doi:10.1111/j.1360-0443.2009.02646.x.
- Williams KE, Reeves KR, Billing CB Jr, et al. A double-blind study evaluating the long-term safety of varenicline for smoking cessation. Curr Med Res Opin. 2007;23(4):793–801.