Efficacy of Varenicline Combined With Nicotine Replacement Therapy vs Varenicline Alone for Smoking Cessation: A Randomized Clinical Trial | Clinical Pharmacy and Pharmacology | JAMA | JAMA Network
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1.
Jha  P, Ramasundarahettige  C, Landsman  V,  et al.  21st-century hazards of smoking and benefits of cessation in the United States.  N Engl J Med. 2013;368(4):341-350.PubMedGoogle ScholarCrossref
2.
Jha  P.  Avoidable global cancer deaths and total deaths from smoking.  Nat Rev Cancer. 2009;9(9):655-664.PubMedGoogle ScholarCrossref
3.
Rigotti  NA.  Strategies to help a smoker who is struggling to quit.  JAMA. 2012;308(15):1573-1580.PubMedGoogle ScholarCrossref
4.
Gonzales  D, Rennard  SI, Nides  M,  et al; Varenicline Phase 3 Study Group.  Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial.  JAMA. 2006;296(1):47-55.PubMedGoogle ScholarCrossref
5.
Jorenby  DE, Hays  JT, Rigotti  NA,  et al; Varenicline Phase 3 Study Group.  Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial.  JAMA. 2006;296(1):56-63.PubMedGoogle ScholarCrossref
6.
Tonstad  S, Tønnesen  P, Hajek  P, Williams  KE, Billing  CB, Reeves  KR; Varenicline Phase 3 Study Group.  Effect of maintenance therapy with varenicline on smoking cessation: a randomized controlled trial.  JAMA. 2006;296(1):64-71.PubMedGoogle ScholarCrossref
7.
Benowitz  NL.  Nicotine addiction.  N Engl J Med. 2010;362(24):2295-2303.PubMedGoogle ScholarCrossref
8.
Prochaska  JJ, Hilton  JF.  Risk of cardiovascular serious adverse events associated with varenicline use for tobacco cessation: systematic review and meta-analysis.  BMJ. 2012;344:e2856.PubMedGoogle ScholarCrossref
9.
Hajek  P, Smith  KM, Dhanji  AR, McRobbie  H.  Is a combination of varenicline and nicotine patch more effective in helping smokers quit than varenicline alone? a randomised controlled trial.  BMC Med. 2013;11:140.PubMedGoogle ScholarCrossref
10.
Ebbert  JO, Burke  MV, Hays  JT, Hurt  RD.  Combination treatment with varenicline and nicotine replacement therapy.  Nicotine Tob Res. 2009;11(5):572-576.PubMedGoogle ScholarCrossref
11.
Heatherton  TF, Kozlowski  LT, Frecker  RC, Fagerström  KO.  The Fagerström Test for Nicotine Dependence: a revision of the Fagerström Tolerance Questionnaire.  Br J Addict. 1991;86(9):1119-1127.PubMedGoogle ScholarCrossref
12.
Welsch  SK, Smith  SS, Wetter  DW, Jorenby  DE, Fiore  MC, Baker  TB.  Development and validation of the Wisconsin Smoking Withdrawal Scale.  Exp Clin Psychopharmacol. 1999;7(4):354-361.PubMedGoogle ScholarCrossref
13.
Fiore  MC, Jaén  CR, Baker  TB,  et al.  Treating Tobacco Use and Dependence: Quick Reference Guide for Clinicians. Rockville, MD: US Dept of Health and Human Services, Public Health Service; 2008.
14.
Besada  NA, Guerrero  AC, Fernandez  MI, Ulibarri  MM, Jiménez-Ruiz  CA.  Clinical experience from a smokers clinic combining varenicline and nicotine gum.  Eur Respir J. 2010;36(suppl 54):462s.Google ScholarCrossref
15.
Cahill  K, Stevens  S, Perera  R, Lancaster  T.  Pharmacological interventions for smoking cessation: an overview and network meta-analysis.  Cochrane Database Syst Rev. 2013;5:CD009329.PubMedGoogle Scholar
16.
Ebbert  JO, Hatsukami  DK, Croghan  IT,  et al.  Combination varenicline and bupropion SR for tobacco-dependence treatment in cigarette smokers: a randomized trial.  JAMA. 2014;311(2):155-163.PubMedGoogle ScholarCrossref
17.
Lindson-Hawley  N, Aveyard  P, Hughes  JR.  Reduction versus abrupt cessation in smokers who want to quit.  Cochrane Database Syst Rev. 2012;11:CD008033.PubMedGoogle Scholar
18.
Lindson-Hawley  N, Aveyard  P, Hughes  JR.  Gradual reduction vs abrupt cessation as a smoking cessation strategy in smokers who want to quit.  JAMA. 2013;310(1):91-92.PubMedGoogle ScholarCrossref
19.
Ossip  DJ, Abrams  SM, Mahoney  MC, Sall  D, Cummings  KM.  Adverse effects with use of nicotine replacement therapy among quitline clients.  Nicotine Tob Res. 2009;11(4):408-417.PubMedGoogle ScholarCrossref
20.
Harrison-Woolrych  M, Paterson  H, Tan  M.  Exposure to the smoking cessation medicine varenicline during pregnancy: a prospective nationwide cohort study.  Pharmacoepidemiol Drug Saf. 2013;22(10):1086-1092.PubMedGoogle Scholar
21.
Kaplan  YC, Olgac Dündar  N, Kasap  B, Karadas  B.  Pregnancy outcome after varenicline exposure in the first trimester [published online February 3, 2014].  Case Rep Obstet Gynecol. doi:10.1155/2014/263981. PubMedGoogle Scholar
Original Investigation
July 9, 2014

Efficacy of Varenicline Combined With Nicotine Replacement Therapy vs Varenicline Alone for Smoking Cessation: A Randomized Clinical Trial

Author Affiliations
  • 1Stellenbosch University, Cape Town, South Africa
  • 2University of Cape Town, Cape Town, South Africa
  • 3Gatesville Melomed Hospital, Cape Town, South Africa
  • 4Christiaan Barnard Memorial Hospital, Cape Town, South Africa
  • 5Rochester Place Medical Centre, Johannesburg, South Africa
  • 6Kingsway Medical Centre, Durban, South Africa
  • 7Synopsis Research Unit, Cape Town, South Africa
JAMA. 2014;312(2):155-161. doi:10.1001/jama.2014.7195
Abstract

Importance  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.

Design, Setting, and Participants  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.

Interventions  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.

Main Outcomes and Measures  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 and Relevance  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.

Trial Registration  clinicaltrials.gov Identifier: NCT01444131

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