title: Effects of Nicotine Patch vs Varenicline vs Combination Nicotine Replacement Therapy on Smoking Cessation at 26 Weeks: A Randomized Clinical Trial.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  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.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01553084.
authors.affiliation: Center for Tobacco Research and Intervention, University of Wisconsin School of Medicine and Public Health, Madison2Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison.
authors.forename: Timothy B
authors.initials: TB
authors.lastname: Baker
authors.affiliation: Center for Tobacco Research and Intervention, University of Wisconsin School of Medicine and Public Health, Madison2Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison.
authors.forename: Megan E
authors.initials: ME
authors.lastname: Piper
authors.affiliation: Department of Medicine, Cardiovascular Medicine, University of Wisconsin School of Medicine and Public Health, Madison.
authors.forename: James H
authors.initials: JH
authors.lastname: Stein
authors.affiliation: Center for Tobacco Research and Intervention, University of Wisconsin School of Medicine and Public Health, Madison2Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison.
authors.forename: Stevens S
authors.initials: SS
authors.lastname: Smith
authors.affiliation: Department of Educational Psychology, University of Wisconsin-Madison.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Bolt
authors.affiliation: Center for Tobacco Research and Intervention, University of Wisconsin School of Medicine and Public Health, Madison.
authors.forename: David L
authors.initials: DL
authors.lastname: Fraser
authors.affiliation: Center for Tobacco Research and Intervention, University of Wisconsin School of Medicine and Public Health, Madison2Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Fiore
mesh_terms: D000328:Adult; D002248:Carbon Monoxide / Q000097:blood; D003376:Counseling; D005260:Female; D006801:Humans; D057194:Intention to Treat Analysis; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D009538:Nicotine / Q000008:administration & dosage* / Q000009:adverse effects; D018722:Nicotinic Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D017063:Outcome Assessment, Health Care; D012907:Smoking / Q000009:adverse effects / Q000097:blood / Q000188:drug therapy*; D016540:Smoking Cessation / Q000379:methods; D013375:Substance Withdrawal Syndrome / Q000628:therapy; D013997:Time Factors; D061485:Tobacco Use Cessation Devices / Q000009:adverse effects; D000068580:Varenicline / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D018722:Nicotinic Agonists; D009538:Nicotine; D002248:Carbon Monoxide; D000068580:Varenicline
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