title: Efficacy of varenicline combined with nicotine replacement therapy vs varenicline alone for smoking cessation: a randomized clinical trial.
abstract: OBJECTIVE
  Behavioral approaches and pharmacotherapy are of proven benefit in assisting smokers to quit, but it is unclear whether combining nicotine replacement therapy (NRT) with varenicline to improve abstinence is effective and safe.
  
  
  OBJECTIVE
  To evaluate the efficacy and safety of combining varenicline and a nicotine patch vs varenicline alone in smoking cessation.
  
  
  METHODS
  Randomized, blinded, placebo-controlled clinical trial with a 12-week treatment period and a further 12-week follow-up conducted in 7 centers in South Africa from April 2011 to October 2012. Four hundred forty-six generally healthy smokers were randomized (1:1); 435 were included in the efficacy and safety analyses.
  
  
  METHODS
  Nicotine or placebo patch treatment began 2 weeks before a target quit date (TQD) and continued for a further 12 weeks. Varenicline was begun 1 week prior to TQD, continued for a further 12 weeks, and tapered off during week 13.
  
  
  METHODS
  Tobacco abstinence was established and confirmed by exhaled carbon monoxide measurements at TQD and at intervals thereafter up to 24 weeks. The primary end point was the 4-week exhaled carbon monoxide-confirmed continuous abstinence rate for weeks 9 through 12 of treatment, ie, the proportion of participants able to maintain complete abstinence from smoking for the last 4 weeks of treatment, as assessed using multiple imputation analysis. Secondary end points included point prevalence abstinence at 6 months, continuous abstinence rate from weeks 9 through 24, and adverse events. Multiple imputation also was used to address loss to follow-up.
  
  
  RESULTS
  The combination treatment was associated with a higher continuous abstinence rate at 12 weeks (55.4% vs 40.9%; odds ratio [OR], 1.85; 95% CI, 1.19-2.89; P = .007) and 24 weeks (49.0% vs 32.6%; OR, 1.98; 95% CI, 1.25-3.14; P = .004) and point prevalence abstinence rate at 6 months (65.1% vs 46.7%; OR, 2.13; 95% CI, 1.32-3.43; P = .002). In the combination treatment group, there was a numerically greater incidence of nausea, sleep disturbance, skin reactions, constipation, and depression, with only skin reactions reaching statistical significance (14.4% vs 7.8%; P = .03); the varenicline-alone group experienced more abnormal dreams and headaches.
  
  
  CONCLUSIONS
  Varenicline in combination with NRT was more effective than varenicline alone at achieving tobacco abstinence at 12 weeks (end of treatment) and at 6 months. Further studies are needed to assess long-term efficacy and safety.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01444131.
authors.affiliation: Stellenbosch University, Cape Town, South Africa.
authors.forename: Coenraad F N
authors.initials: CF
authors.lastname: Koegelenberg
authors.affiliation: Stellenbosch University, Cape Town, South Africa.
authors.forename: Firdows
authors.initials: F
authors.lastname: Noor
authors.affiliation: University of Cape Town, Cape Town, South Africa.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Bateman
authors.affiliation: University of Cape Town, Cape Town, South Africa.
authors.forename: Richard N
authors.initials: RN
authors.lastname: van Zyl-Smit
authors.affiliation: Gatesville Melomed Hospital, Cape Town, South Africa.
authors.forename: Axel
authors.initials: A
authors.lastname: Bruning
authors.affiliation: Christiaan Barnard Memorial Hospital, Cape Town, South Africa.
authors.forename: John A
authors.initials: JA
authors.lastname: O'Brien
authors.affiliation: Rochester Place Medical Centre, Johannesburg, South Africa.
authors.forename: Clifford
authors.initials: C
authors.lastname: Smith
authors.affiliation: Kingsway Medical Centre, Durban, South Africa.
authors.forename: Mohamed S
authors.initials: MS
authors.lastname: Abdool-Gaffar
authors.affiliation: Synopsis Research Unit, Cape Town, South Africa.
authors.forename: Shaunagh
authors.initials: S
authors.lastname: Emanuel
authors.affiliation: Stellenbosch University, Cape Town, South Africa.
authors.forename: Tonya M
authors.initials: TM
authors.lastname: Esterhuizen
authors.affiliation: Stellenbosch University, Cape Town, South Africa.
authors.forename: Elvis M
authors.initials: EM
authors.lastname: Irusen
mesh_terms: D000328:Adult; D001552:Benzazepines / Q000009:adverse effects / Q000627:therapeutic use*; D001944:Breath Tests; D002248:Carbon Monoxide / Q000032:analysis; D018678:Cholinergic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000008:administration & dosage* / Q000009:adverse effects; D011810:Quinoxalines / Q000009:adverse effects / Q000627:therapeutic use*; D016540:Smoking Cessation / Q000379:methods*; D061485:Tobacco Use Cessation Devices; D014029:Tobacco Use Disorder / Q000188:drug therapy*; D016896:Treatment Outcome; D000068580:Varenicline
chemical_list: D001552:Benzazepines; D018678:Cholinergic Agents; D011810:Quinoxalines; D009538:Nicotine; D002248:Carbon Monoxide; D000068580:Varenicline