Combining varenicline and nicotine patches: a randomized controlled trial study in smoking cessation

BMC Medicine

Cristina Masuet-Aumatell¹  Antoni Baena²  Sergio Morchon¹  Josep M Ramon¹ 

[1]Medical Sciences Department, School of Medicine, Barcelona University, Feixa Llarga s/n 08907 Hospitalet de Llobregat, Barcelona, Spain

[2]Bellvitge Biomedical Research Institute (IDIBELL), Smoking Cessation Clinic, Preventive Medicine Department, Bellvitge University Hospital, Feixa Llarga s/n 08907 Hospitalet de Llobregat, Barcelona, Spain

关键词: Randomized trial;    Combination therapy;    Nicotine patches;    Varenicline;    Smoking cessation;   

Others  :  1121404
DOI  :  10.1186/s12916-014-0172-8

 received in 2014-07-10, accepted in 2014-09-04,  发布年份 2014

【 摘 要 】

Background

Some smokers may benefit from a therapy that combines different nicotine replacement therapies (NRT) or drugs with different mechanisms of action.

The aim of this study was to determine the efficacy of the combined therapy of varenicline and nicotine patches versus varenicline monotherapy.

Methods

Three hundred forty-one smokers who smoked 20 or more cigarettes per day were recruited from a smoking cessation clinic between February 2012 and June 2013. The participants were randomized to receive a varenicline plus nicotine patch of 21 mg every 24 hours (170) or varenicline plus a placebo patch (171). All of the smokers received a standard 12-week course of varenicline and an 11-week course of either the placebo patch or the active patch after the target quit day. Both groups received behavioral support. The primary outcome was continuous abstinence for weeks 2 through 12 confirmed by exhaled levels of carbon monoxide. Post hoc subgroup analyses were performed to evaluate the treatment effects for a specific endpoint in subgroups of smokers.

Results

The combination of the nicotine patch with varenicline was not associated with higher rates of continuous abstinence at 12 weeks (39.1% versus 31.8%; odds ratio (OR) 1.24; 95% confidence interval (CI) 0.8 to 2.6) and 24 weeks (32.8% versus 28.2%; OR 1.17; 95% CI 0.4 to 1.9). When participants were analyzed by subgroups according to cigarette consumption, the abstinence rates among smokers who smoked more than 29 cigarettes per day at 12 weeks (OR 1.39; 95% CI 1.2 to 2.5) and 24 weeks (OR 1.46; 95% CI 1.2 to 2.8) were significantly higher in the combination group. Other post hoc analyses based on level of dependence and previous quit attempts did not show subgroup differences. No differences between the groups for the reported adverse events were observed (χ2 value 0.07; P 0.79).

Conclusions

The combination of varenicline with the nicotine patch does not improve abstinence rates at 12 and 24 weeks compared with varenicline used as monotherapy when all smokers were analyzed as a whole, independent of consumption level.

Trial registration

This study is registered at clinicaltrial.gov (NCT01538394 webcite).

【 授权许可】

   
2014 Ramon et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】

• [1]Fiore MC, Jaen CR, Baker TB, Bailey WC, Benowitz NL, Curry SJ, Dorfman SF, Froelicher ES, Goldstein MG, Healton CG, Henderson PN, Heyman RB, Koh HK, Kottke TE, Lando HA, Mecklenburg RE, Mermelstein RJ, Mullen PD, Orleans CT, Robinson L, Stitzer ML, Tommasello AC, Villejo L, Wewers ME: Treating tobacco use and dependence: 2008 update–clinical pbiractice guideline. US Department of Health and Human Services, Public Health Service, Rockville, MD; 2008.
• [2]Mills EJ, Wu P, Lockhart I, Thorlund K, Puhan M, Ebbert JO: Comparisons of high-dose and combination nicotine replacement therapy, varenicline, and bupropion for smoking cessation: a systematic review and multiple treatment meta-analysis. Ann Med 2012, 44:588-597.
• [3]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
• [4]Shah SD, Wilken LA, Winkler SR, Lin SJ: Systematic review and meta-analysis of combination therapy for smoking cessation. J Am Pharm Assoc 2008, 48:659-665.
• [5]Williams KE, Reeves KR, Billing CB Jr, Pennington AM, Gong J: A double-blind study evaluating the long-term safety of varenicline for smoking cessation. Curr Med Res Opin 2007, 23:793-801.
• [6]Oncken C, Gonzales D, Nides M, Rennard S, Watsky E, Billing CB, Anziano R, Reeves K: Efficacy and safety of the novel selective nicotinic acetylcholine receptor partial agonist, varenicline, for smoking cessation. Arch Intern Med 2006, 166:1571-1577.
• [7]Ebbert JO, Burke MV, Hays JT, Hurt RD: Combination treatment with varenicline and nicotine replacement therapy. Nicotine Tob Res 2009, 11:572-576.
• [8]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. BioMed Central Full Text
• [9]Koegelenberg CF, Noor F, Bateman ED, Van Zyl-Smit RN, Bruning A, O’Brien JA, Smith C, Abdool-Gaffar MS, Emanuel S, Esterhuizen TM, Irusen EM: Efficacy of varenicline combined with nicotine replacement therapy vs varenicline alone for smoking cessation: a randomized clinical trial. JAMA 2014, 312:155-161.
• [10]Beck AT, Steer RA, Brown GK: Depression Inventory Manual. Psychological Corp, San Antonio, TX; 1996.
• [11]Hamilton M: The assessment of anxiety states by rating. Br J Med Psychol 1959, 32:50-55.
• [12][http://www.uvm.edu/~hbpl/?Page=minnesota/default.html] webcite Hughes JR: Minnesota nicotine Withdrawal Scale-Revised. Accessed December 11,2013.
• [13]Beck AT, Kovacs M, Weissman A: Assessment of suicidal intention: the scale for suicide ideation. J Consult Clin Psychol 1979, 47:343-352.
• [14]Hughes JR, Keely JP, Niaura RS, Ossip-Klein DJ, Richmond RL, Swan GE: Measures of abstinence in clinical trials: issues and recommendations. Nicotine Tob Res 2003, 5:13-25.
• [15]West R, Hajek P, Stead L, Stapleton J: Outcome criteria in smoking cessation trials: proposal for common standard. Addiction 2005, 100:299-303.
• [16]Hajek P, West R: Commentary on Smolkowski,et al(2010): Why is it important to assume that non-responders in tobacco cessation trials have relapsed? Addiction 2010, 105:1016-1017.
• [17]Japuntich SJ, Leventhal AM, Piper ME, Bolt DM, Roberts LJ, Fiore MC, Baker TB: Smoker characteristics and smoking-cessation milestones. Am J Prev Med 2011, 40:286-294.
• [18]Ebbert JO, Hatsukami DK, Croghan IT, Schroeder DR, Allen SS, Hays JT, Hurt RD: Combination varenicline and bupropion SR for tobacco-dependence treatment in cigarette smokers. A randomized trial. JAMA 2014, 311:155-163.
• [19]Miller WR, Rollnick S: Motivational interviewing: preparing people for change. Guildford Press, New York; 2002.