Effect of Combination Treatment With Varenicline and Nicotine Patch on Smoking Cessation Among Smokers Who Drink Heavily: A Randomized Clinical Trial

Abstract

Importance: The concurrent use of both tobacco and alcohol causes substantial disease and early mortality, and smokers who drink heavily tend to be less successful in smoking cessation than smokers who do not. Although varenicline combined with nicotine replacement therapy for smoking cessation has been examined among smokers who do not drink heavily, this combination treatment has not yet been examined among smokers who drink heavily.

Objective: To determine whether combined treatment with varenicline tartrate and nicotine patch improves continuous abstinence from cigarette smoking among smokers who drink heavily.

Design, setting, and participants: This double-blind, placebo-controlled, superiority randomized clinical trial evaluated combined treatment with varenicline and nicotine patch compared with placebo and nicotine patch for smoking cessation (primary outcome) and drinking behavior (secondary outcome) among smokers who drink heavily. The clinical trial was conducted at 2 outpatient sites in Chicago, Illinois, with enrollment from March 26, 2018, to February 14, 2020. The 122 participants were recruited from the community via social media and public transit advertisements and equally randomized to the 2 treatment groups, which were stratified by sex and smoking behavior. Eligible participants smoked between 5 and 30 cigarettes per day and drank heavily (>14 drinks per week for men or >7 drinks per week for women and ≥1 heavy drinking day [defined as >5 drinks per occasion for men or >4 drinks per occasion for women] per month for the past year) and had a desire to quit smoking.

Interventions: Varenicline tartrate, 1.0 mg, twice daily or matching placebo pills twice daily for 12 weeks. Nicotine patch at manufacturer-recommended doses for 10 weeks and brief individual smoking cessation counseling the week before the quit date and on the quit date.

Main outcomes and measures: The primary outcome was self-reported continuous cigarette abstinence through weeks 9 to 12; abstinence was biochemically confirmed at the week 12 study visit. Secondary outcomes were the frequency of weekly drinking and weekly heavy drinking during the study period.

Results: Among 122 participants (mean [SD] age, 44.0 [12.4] years; 67 men [54.9%]), 61 were randomly assigned to receive combined treatment with varenicline and nicotine patch (varenicline group), and 61 were randomly assigned to receive placebo and nicotine patch (placebo group). A total of 54 participants (44.3%) self-identified as Black, 56 (45.9%) as White, and 12 (9.8%) as other races (including American Indian or Alaska Native, Asian, >1 race, and unspecified race). A total of 8 participants (6.6%) self-identified as Hispanic and 114 (93.4%) as non-Hispanic ethnicity. Study retention to 12 weeks was 89%. The intention-to-treat analyses showed higher smoking cessation rates during weeks 9 to 12 in the varenicline group vs the placebo group (27 participants [44.3%] vs 17 participants [27.9%]; odds ratio, 2.20; 95% CI, 1.01-4.80; P = .047) and lower likelihood of relapse throughout treatment in the varenicline group relative to the placebo group (hazard ratio, 0.62; 95% CI, 0.40-0.96; P = .03). Both treatments were well tolerated; however, compared with participants in the placebo group, those in the varenicline group experienced more adverse effects, with 5 participants in the varenicline group discontinuing medication due to adverse effects.

Conclusions and relevance: In this study, combined treatment with varenicline and nicotine patch was more effective than placebo and nicotine patch for smoking cessation among smokers who drink heavily. The combination treatment had no effect on alcohol consumption, with both groups showing significant reductions. Combination treatment with varenicline and nicotine patch may be a viable option for smokers who drink heavily.

Trial registration: ClinicalTrials.gov Identifier: NCT02859142.

Conflict of interest statement

Conflict of Interest Disclosures: Dr King reported receiving grants from Pfizer during the conduct of the study and personal fees from the Respiratory Health Association outside the submitted work. Dr de Wit reported being on the board of directors of PharmAla Biotech; being a scientific advisor to Awakn Life Sciences, Gilgamesh Pharmaceuticals, and Schedule I Therapeutics; and receiving research support from the Beckley Foundation outside the submitted work. Dr Grant reported receiving grants from Biohaven Pharmaceuticals, Otsuka Pharmaceutical Company, and Promentis Pharmaceuticals outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. Study Flow Diagram

Figure 2.. Cigarette Smoking Outcomes by Treatment Group

Participants in the varenicline group received varenicline tartrate, 1.0 mg, twice daily and nicotine patch. Participants in the placebo group received matching placebo pills twice daily and nicotine patch. A total of 61 participants were in each group. B, Day 0 indicates the smoking cessation day, which corresponded to the first day of the full medication dose and nicotine patch.

Figure 3.. Alcohol Drinking Outcomes by Treatment Group

Participants in the varenicline group received varenicline tartrate, 1.0 mg, twice daily and nicotine patch. Participants in the placebo group received matching placebo pills twice daily and nicotine patch. Analysis included 109 of 122 participants (89.3%) who completed active treatment. Baseline refers to the mean of the 4-week period before enrollment, and week 0 was the week before the smoking cessation date during which medication was initiated. For baseline drinks per week, data from 3 participants (with outlier values >3 SD higher than the mean) were normalized to 3 SD of the sample mean before analysis. Generalized estimating equation analyses were based on mean drinking days per week and heavy drinking days per week. Each week was divided by a constant of 7 for ease of presenting percentages of drinking days and heavy drinking days. Heavy drinking days were defined as 5 or more drinks per occasion for men and 4 or more drinks per occasion for women.