title: Effect of varenicline on smoking cessation through smoking reduction: a randomized clinical trial.
abstract: OBJECTIVE
  Some cigarette smokers may not be ready to quit immediately but may be willing to reduce cigarette consumption with the goal of quitting.
  
  
  OBJECTIVE
  To determine the efficacy and safety of varenicline for increasing smoking abstinence rates through smoking reduction.
  
  
  METHODS
  Randomized, double-blind, placebo-controlled, multinational clinical trial with a 24-week treatment period and 28-week follow-up conducted between July 2011 and July 2013 at 61 centers in 10 countries. The 1510 participants were cigarette smokers who were not willing or able to quit smoking within the next month but willing to reduce smoking and make a quit attempt within the next 3 months. Participants were recruited through advertising.
  
  
  METHODS
  Twenty-four weeks of varenicline titrated to 1 mg twice daily or placebo with a reduction target of 50% or more in number of cigarettes smoked by 4 weeks, 75% or more by 8 weeks, and a quit attempt by 12 weeks.
  
  
  METHODS
  Primary efficacy end point was carbon monoxide-confirmed self-reported abstinence during weeks 15 through 24. Secondary outcomes were carbon monoxide-confirmed self-reported abstinence for weeks 21 through 24 and weeks 21 through 52.
  
  
  RESULTS
  The varenicline group (n = 760) had significantly higher continuous abstinence rates during weeks 15 through 24 vs the placebo group (n = 750) (32.1% for the varenicline group vs 6.9% for the placebo group; risk difference (RD), 25.2% [95% CI, 21.4%-29.0%]; relative risk (RR), 4.6 [95% CI, 3.5-6.1]). The varenicline group had significantly higher continuous abstinence rates vs the placebo group during weeks 21 through 24 (37.8% for the varenicline group vs 12.5% for the placebo group; RD, 25.2% [95% CI, 21.1%-29.4%]; RR, 3.0 [95% CI, 2.4-3.7]) and weeks 21 through 52 (27.0% for the varenicline group vs 9.9% for the placebo group; RD, 17.1% [95% CI, 13.3%-20.9%]; RR, 2.7 [95% CI, 2.1-3.5]). Serious adverse events occurred in 3.7% of the varenicline group and 2.2% of the placebo group (P = .07).
  
  
  CONCLUSIONS
  Among cigarette smokers not willing or able to quit within the next month but willing to reduce cigarette consumption and make a quit attempt at 3 months, use of varenicline for 24 weeks compared with placebo significantly increased smoking cessation rates at the end of treatment, and also at 1 year. Varenicline offers a treatment option for smokers whose needs are not addressed by clinical guidelines recommending abrupt smoking cessation.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01370356.
authors: Mayo Clinic, Rochester, Minnesota.
authors: Jon O
authors: JO
authors: Ebbert
authors: Department of Psychiatry, University of Vermont, Burlington, Vermont.
authors: John R
authors: JR
authors: Hughes
authors: Health Behaviour Research Centre, Department of Epidemiology and Public Health, University College London, United Kingdom.
authors: Robert J
authors: RJ
authors: West
authors: Division of Pulmonary, Critical Care, Sleep, and Allergy, University of Nebraska Medical Center, Omaha.
authors: Stephen I
authors: SI
authors: Rennard
authors: Pfizer Inc, New York, New York.
authors: Cristina
authors: C
authors: Russ
authors: Pfizer Inc, New York, New York.
authors: Thomas D
authors: TD
authors: McRae
authors: Pfizer Inc, New York, New York.
authors: Joan
authors: J
authors: Treadow
authors: Pfizer Inc, New York, New York.
authors: Ching-Ray
authors: CR
authors: Yu
authors: Pfizer Inc, New York, New York.
authors: Michael P
authors: MP
authors: Dutro
authors: Pfizer Inc, New York, New York.
authors: Peter W
authors: PW
authors: Park
mesh_terms: D000328:Adult; D000368:Aged; D001552:Benzazepines / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018722:Nicotinic Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D011810:Quinoxalines / Q000009:adverse effects / Q000627:therapeutic use*; D016540:Smoking Cessation / Q000379:methods*; D014029:Tobacco Use Disorder / Q000188:drug therapy*; D000068580:Varenicline; D055815:Young Adult
chemical_list: D001552:Benzazepines; D018722:Nicotinic Agonists; D011810:Quinoxalines; D000068580:Varenicline