Varenicline is a selective partial agonist/antagonist of the α4β2 nicotine acetylcholine receptor and it is used to assist in smoking cessation1. When varenicline binds to the α4β2 nicotine receptor, it stimulates the release of small amounts of dopamine. Released dopamine reduces nicotine withdrawal symptoms. In addition, varenicline has an antagonistic effect. By blocking the nicotine from binding to its receptor, varenicline reduces the rewarding aspects of tobacco smoking2. The efficacy of varenicline was well demonstrated in randomized controlled trials from several countries3,4,5. In a meta-analysis, continuous abstinence at 6 months or longer was higher with varenicline than with placebo6. Although the clinical evidence supporting the varenicline is strong, the situation might be different in a real clinical setting. Usually, participants of clinical trials are well educated about the harmful effects of smoking. For this reason, they are more likely to be motivated and compliant with drug therapy compared to average, real smokers. In our previous study, compliance to the 12-week course of varenicline therapy was only 15% in real clinical practice setting7. The long-term efficacy of varenicline is another important, unexplored issue. Temporal quitters experience great difficulty in permanently abstaining from smoking and smoking can relapse even several years after cessation8. However, most studies of varenicline for smoking cessation have focused on the endpoint of abstinence at 1 year9. Varenicline has been available in South Korea since 2007. With accumulated experience, we attempted to evaluate the long-term abstinence status of varenicline users from smoking who were prescribed the drug at our clinic. We also evaluated the preferred ways of smoking cessation among current smokers who had experienced varenicline.

The prescription of varenicline was available at our clinic since June 2007. In the present study, we evaluated the seven-day continuous abstinence rate from smoking among varenicline users. Telephone interviews were done from May 2010 to June 2011. We attempted to contact them around the date of first, second, or third anniversary according to their first prescription of varenicline. Among the 250 who were prescribed varenicline, 133 (53.2%) were available for the telephone interview. Seven-day continuous abstinence rates were 43.6% (17/39), 30.6% (11/36), and 32.8% (19/58) around the first, second, and third anniversary dates, respectively.

In an open-label randomized trial of 757 smokers, the 52-week continuous abstinence rate (week, 9-52) was 26.1% among recipients of a 12-week standard regimen of varenicline10. In another study, carbon monoxide-confirmed continuous quit rates from week 4 to week 52 was 14.4% in varenicline users11. Compared to these studies, our abstinence rate of 43.6% at the first anniversary date is high. However, there was a difference in the measured way of smoking cessation between our study and the previous ones. The above studies were well-designed and controlled clinical trials and most of the participants completed the targeted period of varenicline prescription. As such, they were able to measure the continuous abstinence rate for almost a year. In the present study which reflects real clinical practice, only 15% of patients completed a 12-week course of varenicline. For this reason, we measured the 7-day continuous abstinence rate around the first, second, or third anniversary dates since the first dose of varenicline. It may have increased the abstinence rate compared to the studies which evaluated continuous abstinence rate for longer period. In addition, we were able to contact slightly over 50% of varenicline users. Considering the reasons for unavailability (no response to the registered phone number, no valid phone number at the time of contact, no purchase of varenicline, and refusal to participate in the telephone interview), the chances are high that we selected those who were more willing to follow the recommendation of doctors for smoking cessation (Figure 1). In addition, we surveyed smoking status only by self-reported telephone interview. Objective confirmation of smoking cessation by carbon monoxide- breath test or urine cotinine test could have selected out false quitters. All of these factors may have contributed to the higher quitting rate at one year since the first experience of varenicline in our study.

Almost all studies of varenicline have evaluated long-term efficacy at 52 weeks or less3,4,5,7,10,11. There were a few study about long term abstinence rate of barenicline12,13. Hsueh et al.12 demonstrated the 3-year continuous abstinence rate was 18.9% in 8 weeks varenicline user. In 3-year follow-up data in Turkey, the smoking cessation rate was 32.5% in varenicline group13. In the present study, we determined the smoking status of varenicline users at 1, 2, and 3 years since the first prescription. The 7-day continuous abstinence rates maintained a high range not only in the first year but also in the second and third years (Figure 2). In addition, the average non-smoking period increased with each passing year (6.8±4.42, 16.3±9.41, and 26.9±13.10 months, respectively). Considering these findings, varenicline may be helpful in the long-term abstinence from smoking among some users.

Successful quitters experience difficulty in remaining abstinent from smoking permanently. Smoking can relapse after several years of successful abstinence. Long-term tracking revealed that 35% to 40% of patients relapse between one and 5 years after quitting14,15. Nearly two-thirds of smokers who relapse report wanting to quit again within 30 days. Therefore, they should be encouraged to re-start a smoking cessation program as soon as possible16. It would be helpful to remind smokers that most smokers require multiple attempts at smoking cessation before permanently quitting. If a previous medication was helpful, the same therapy is typically recommended for the next trial. In our telephone survey, 70% of current smokers who experienced varenicline wanted to stop smoking cessation in the future. However, nearly half of them selected their own will-power for the cessation method and only one-fourth chose varenicline. Notably, the proportion of subjects with severe nicotine dependence increased successively each year after the first prescription of varenicline (Figure 3). Too much dependence on their own will and high level of nicotine dependence would make their next attempt of smoking cessation pessimistic. It is well-known that only one-fourth of smokers who try to quit seek help, and even fewer use the most effective treatment17. Our study found that successful quitters were older, had better compliance to a 12-week course, and had taken varenicline longer compared to those who failed (Table 2). Smokers should be persuaded to use evidence-based methods for a designated period of time for their next attempts at smoking cessation.

This study has several limitations. Although we prospectively interviewed varenicline users by telephone, their experience with the drug was not strictly controlled in a clinical practice. The number of respondents was 133 out of 250 total patients, indicating that slightly less than half of varenicline users were unavailable for the survey. In addition, we relied on the responses of the subjects for smoking status without objective measurement of exhaled carbon monoxide or a urine cotinine test. Finally the success of non-smoking was assessed by a seven-day continuous abstinence rate which is too short to evaluate the long-term efficacy of anti-smoking aids. Nonetheless, this study provides valuable information about the long-term abstinence state from smoking among varenicline users as far as 3 years since the first prescription in real clinical practice.

In conclusion, the use of varenicline was associated with long-term smoking cessation as long as three years after its first prescription. Old age, good compliance to a 12-week course, and a longer duration of varenicline use were related to successful smoking cessation. Failed quitters should be encouraged to adopt proven ways for subsequent attempts to quit smoking.