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Original Investigation |

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

Timothy B. Baker, PhD1,2; Megan E. Piper, PhD1,2; James H. Stein, MD3; Stevens S. Smith, PhD1,2; Daniel M. Bolt, PhD4; David L. Fraser, MS1; Michael C. Fiore, MD, MPH, MBA1,2
[+] Author Affiliations
1Center for Tobacco Research and Intervention, University of Wisconsin School of Medicine and Public Health, Madison
2Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison
3Department of Medicine, Cardiovascular Medicine, University of Wisconsin School of Medicine and Public Health, Madison
4Department of Educational Psychology, University of Wisconsin–Madison
JAMA. 2016;315(4):371-379. doi:10.1001/jama.2015.19284.
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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

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Flow of Participants From a Longitudinal Cohort and a Community-Based Cohort in a Trial of Nicotine Patch vs Varenicline vs C-NRT for Smoking Cessation

C-NRT indicates combination nicotine replacement therapy. Cohort 1 comprises participants recruited from an ongoing longitudinal study of smokers, the Wisconsin Smokers Health Study,14,16,17 while cohort 2 participants were recruited for this study from the community via media and community outreach.

aExclusion due to diagnosis of or treatment for schizophrenia, a psychotic disorder, or bipolar disorder in the last 10 years.

bExclusion due to hospitalization for stroke, myocardial infarction, congestive heart failure, or diabetes in the last year.

cExclusion reasons: carotid stenosis (60% visual or peak systolic velocity 130 cm/s), n = 50; cardiac ischemia, n = 16; cardiac arrhythmia, n = 15; long QT interval, n = 12; other, n = 31.

dData on withdrawals were collected through 52 weeks.

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