Effects of Nicotine Patch vs Varenicline vs Combination Nicotine Replacement Therapy on Smoking Cessation at 26 Weeks: A Randomized Clinical Trial.

IMPORTANCE: Smoking cessation medications are routinely used in health care; it is vital to identify medications that most effectively treat this leading cause of preventable mortality.

OBJECTIVE: To compare the efficacies of varenicline, combination nicotine replacement therapy (C-NRT), and the nicotine patch for 26-week quit rates.

DESIGN, SETTING, AND PARTICIPANTS: Three-group randomized intention-to-treat clinical trial occurring from May 2012 to November 2015 among smokers recruited in the Madison, Wisconsin, and Milwaukee, Wisconsin, communities; 65.5% of smokers offered the study (2687/4102) refused participation prior to randomization.

INTERVENTIONS: Participants were randomized to one of three 12-week open-label smoking cessation pharmacotherapy groups: (1) nicotine patch only (n = 241); (2) varenicline only (including 1 prequit week; n = 424); and (3) C-NRT (nicotine patch + nicotine lozenge; n = 421). Six counseling sessions were offered.

MAIN OUTCOMES AND MEASURES: The primary outcome was carbon monoxide-confirmed self-reported 7-day point-prevalence abstinence at 26 weeks. Secondary outcomes were carbon monoxide-confirmed self-reported initial abstinence, prolonged abstinence at 26 weeks, and point-prevalence abstinence at weeks 4, 12, and 52.

RESULTS: Among 1086 smokers randomized (52% women; 67% white; mean age, 48 years; mean of 17 cigarettes smoked per day), 917 (84%) provided 12-month follow-up data. Treatments did not differ on any abstinence outcome measure at 26 or 52 weeks, including point-prevalence abstinence at 26 weeks (nicotine patch, 22.8% [55/241]; varenicline, 23.6% [100/424]; and C-NRT, 26.8% [113/421]) or at 52 weeks (nicotine patch, 20.8% [50/241]; varenicline, 19.1% [81/424]; and C-NRT, 20.2% [85/421]). At 26 weeks, the risk differences for abstinence were, for patch vs varenicline, -0.76% (95% CI, -7.4% to 5.9%); for patch vs C-NRT, -4.0% (95% CI, -10.8% to 2.8%); and for varenicline vs C-NRT, -3.3% (95% CI, -9.1% to 2.6%). All medications were well tolerated, but varenicline produced more frequent adverse events than did the nicotine patch for vivid dreams, insomnia, nausea, constipation, sleepiness, and indigestion.

CONCLUSIONS AND RELEVANCE: Among adults motivated to quit smoking, 12 weeks of open-label treatment with nicotine patch, varenicline, or C-NRT produced no significant differences in biochemically confirmed rates of smoking abstinence at 26 weeks. The results raise questions about the relative effectiveness of intense smoking pharmacotherapies.

TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01553084.