Question
Does combining varenicline with the nicotine patch or extending cessation treatment duration increase smoking abstinence compared with the standard length of therapy with varenicline only?
Findings
In this randomized clinical trial that included 1251 participants smoking 5 cigarettes/d or more, treatment with varenicline monotherapy for 12 weeks, varenicline plus nicotine patch for 12 weeks, varenicline monotherapy for 24 weeks, and varenicline plus nicotine patch for 24 weeks resulted in 7-day point prevalence abstinence rates at 52 weeks of 25.1%, 23.6%, 24.4%, and 25.1%, respectively. None of the comparisons was statistically significant.
Meaning
These findings do not support the use of combined varenicline plus nicotine patch vs varenicline monotherapy or of 24-week vs 12-week treatment for smoking cessation.
Importance
Smoking cessation medications are routinely used in health care. Research suggests that combining varenicline with the nicotine patch, extending the duration of varenicline treatment, or both, may increase cessation effectiveness.
Objective
To compare combinations of varenicline plus the nicotine or placebo patch vs combinations used for either 12 weeks (standard duration) or 24 weeks (extended duration).
Design, Settings, and Participants
Double-blind, 2 × 2 factorial randomized clinical trial conducted from November 11, 2017, to July 9, 2020, at 1 research clinic in Madison, Wisconsin, and at 1 clinic in Milwaukee, Wisconsin. Of the 5836 adults asked to participate in the study, 1251 who smoked 5 cigarettes/d or more were randomized.
Interventions
All participants received cessation counseling and were randomized to 1 of 4 medication groups: varenicline monotherapy for 12 weeks (n = 315), varenicline plus nicotine patch for 12 weeks (n = 314), varenicline monotherapy for 24 weeks (n = 311), or varenicline plus nicotine patch for 24 weeks (n = 311).
Main Outcomes and Measures
The primary outcome was carbon monoxide–confirmed self-reported 7-day point prevalence abstinence at 52 weeks.
Results
Among 1251 patients who were randomized (mean [SD] age, 49.1 [11.9] years; 675 [54.0%] women), 751 (60.0%) completed treatment and 881 (70.4%) provided final follow-up. For the primary outcome, there was no significant interaction between the 2 treatment factors of medication type and medication duration (odds ratio [OR], 1.03 [95% CI, 0.91 to 1.17]; P = .66). For patients randomized to 24-week vs 12-week treatment duration, the primary outcome occurred in 24.8% (154/622) vs 24.3% (153/629), respectively (risk difference, −0.4% [95% CI, −5.2% to 4.3%]; OR, 1.01 [95% CI, 0.89 to 1.15]). For patients randomized to varenicline combination therapy vs varenicline monotherapy, the primary outcome occurred in 24.3% (152/625) vs 24.8% (155/626), respectively (risk difference, 0.4% [95% CI, −4.3% to 5.2%]; OR, 0.99 [95% CI, 0.87 to 1.12]). Nausea occurrence ranged from 24.0% to 30.9% and insomnia occurrence ranged from 24.4% to 30.5% across the 4 groups.
Conclusions and Relevance
Among adults smoking 5 cigarettes/d or more, there were no significant differences in 7-day point prevalence abstinence at 52 weeks among those treated with combined varenicline plus nicotine patch therapy vs varenicline monotherapy, or among those treated for 24 weeks vs 12 weeks. These findings do not support the use of combined therapy or of extended treatment duration.
Trial Registration
ClinicalTrials.gov Identifier: NCT03176784