Varenicline versus transdermal nicotine patch for smoking cessation: results from a randomised open-label trial.

Background: Varenicline is a relatively new treatment for smoking cessation and has demonstrated greater efficacy than placebo or sustained release bupropion. Transdermal nicotine replacement has long been a cornerstone in smoking cessation therapy.

Objective: The purpose of this study was to compare 12 weeks of standard treatment with varenicline versus a 10 week standard treatment with transdermal nicotine patches for smoking cessation using an open-label design.

Methods: This was a 52 week, open-label, randomized, multicenter, controlled trial. It took place in 5 countries between January 2005 and June 2006. The patients were enrolled from a total of 24 centers and were randomly assigned to receive varenicline 1mg BID for 12 weeks or transdermal NRT titrating down from 21mg/day for 10 weeks. There were a total of 757 patients randomized to the study. Patients were included in the study who were smokers (at least 15/day), ages 18-75, BMI 15-38 kg/m2. Patients were excluded who had history of cancer or psychological illness, drug or alcohol dependence within the last year, renal or hepatic impairment, systolic BP >150 or diastolic >95, and who were taking any medications at home that may interfere with the study. The primary outcome was a chemically confirmed (exhaled carbon monoxide < 10ppm) self-reported continuous abstinence rate (CAR) at the end of the treatment phase. Secondary outcome measures were the CAR at weeks 24 and 52, the measures of craving, withdrawal, and smoking satisfaction. The study used a modified intent-to-treat approach to data handling. The power of the study was estimated to be 90% if each group had a sample size of 365 patients.

Results: 65.7% of the patients randomized to the varenicline group completed the study and 62.2% of the patients randomized to the NRT group completed the study. 55.9% of the varenicline group vs. 43.2% of the NRT group were nonsmokers for the last 4 weeks of treatment (p<0.001). The CAR at weeks 24 and 52 did not show significant findings, though varenicline had better abstinence rates. The secondary endpoints for the measures of craving, withdrawal, and smoking satisfaction showed  results in favor of varenicline with p<0.001.

Strengths: This study had a good rationale and enrolled a sufficient number of patients. They used only patients motivated to stop smoking and provided standardized counseling to all participants by phone or at clinic visits.

Weaknesses: Some of the limitations were the study was open-label, compliance was not addressed, and the study was funded by Pfizer Corporation which manufactures varenicline. Some of the measures of variability were misleading and inappropriately used. Over 84% of the patients in the varenicline group reported an adverse event. Nearly one-third of the initial participants withdrew from both study groups which is a problem in the intent-to-treat analysis. The study excluded patients with unstable medical conditions or psychological illness which limits the extrapolation potential. The study included a large percentage of patients in the NRT group that had previously tried NRT without success. The exhaled CAR test is not indicative of abstinence over a significant period of time, such as the last 4 weeks, which was used in the primary outcome measure.

Conclusion: Varenicline may be more effective than nicotine replacement patches in overall healthy patients but this study did not show that very well. The weaknesses in the study far outweigh the strengths. There was statistical significance shown at the end of the treatment phase but the significance had weaned by the end of the trial. Even with the improvement in abstinence percentage with varenicline there was also an increase in adverse events. Future studies need to have longer durations, a better abstinence testing method, less conflicts of interest, and a double-blinded method.

Aubin HJ, Bobak A, Britton JR, Oncken C, Billing CB, Gong J, et al. Varenicline versus transdermal nicotine patch for smoking cessation: results from a randomised open-label trial. Thorax. 2008;68:717-724. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18263663. Accessed 10/02/2008.

Kari E. McDonald, Pharm.D. Candidate