Smokers' Characteristics Associated with Successful Smoking Cessation Undergoing Pharmacotherapy in Slovenia

Tobacco use is a leading preventable risk factor for noncommunicable chronic diseases and premature death worldwide, leading to more than eight million deaths and 170.9 million disability-adjusted life-years lost each year (1). In 2019, more than one billion individuals worldwide were tobacco users. In Slovenia, the prevalence of smoking is 27.9%, which is higher than the EU average of 26.1% (2). According to the Global Burden of Disease study, in 2019 smoking was the second most important risk factor for female deaths and most important factor for male deaths worldwide (3). There is strong scientific evidence that tobacco use inflicts harm on almost every organ in the human body and has detrimental effects on overall health throughout one's lifetime (4), but tobacco users are most at risk for developing lung cancer, chronic obstructive pulmonary disease (COPD) and ischemic heart disease due to smoking (5). Therefore, reducing tobacco use is essential for improving public health and limiting the tobacco epidemic (6).

Smoking also represents a heavy economic burden for healthcare systems throughout the world (3). This includes direct costs (costs of inpatient care, outpatient visits, drugs and diagnostic tests, transportation costs) and indirect costs (productivity lost, the cost of premature retirement and morbidity costs) (7). There are different approaches to limiting tobacco consumption and lowering the cost of treating patients for the effects of tobacco use. These efforts include various non-pharmacological smoking cessation programmes (8), the use of nicotine substitutes and pharmacotherapy (9). Thus smokers in the European Union (EU) approach smoking cessation differently (8,9,10). In Slovenia, the screening for smoking and tobacco use is carried out by registered nurses who are part of the family medicine (FM) team. Smokers are invited to attend individual or group smoking cessation programmes in Health Promotion Centres. In countries where prescription medicines are available, smokers may be offered this therapy to support the smoking cessation process.

In recent literature, successful smoking cessation has been correlated to factors such as age, gender, education level, cigarette consumption, past quitting attempts, self-efficacy in quitting, presence of smoking family members, household smoking restrictions and nicotine dependency (11,12,13,14). Identifying potential respondents for smoking cessation pharmacotherapy based on nicotine dependency involves assessing the level of nicotine dependency of individuals. The two most used questionnaires used to evaluate nicotine dependency are the Fagerström Test for Nicotine Dependence (FTND) and Heaviness of Smoking Index (HSI). FTND and HIS questionnaires had substantial agreement in measuring high levels of nicotine dependency (15).

There is strong scientific evidence that FTND score is associated with smoking cessation success (16,17,18). However, the association of nicotine dependency and the role of pharmacotherapy to support the smoking cessation process has not yet been studied in Slovenia. Therefore, the aim of this study was to explore the association between the smokers' characteristics and the success of pharmacotherapy for smoking cessation in Slovenian smokers.

This study showed that almost a quarter of smokers undergoing pharmacotherapy successfully quit smoking for a 24-week interval. The statistically significant predictors of smoking cessation success were nicotine dependence and adherence to pharmacotherapy.

The cross-sectional analysis that was performed aimed to investigate factors associated with the success of smoking cessation facilitated by pharmacotherapy. Out of 715 invited participants, 24.6% opted to attempt smoking cessation using prescription medications, specifically cytisine and varenicline, with a success rate of 24.3% over the 24-week observation period.

The univariate analysis among 715 invited participants (Table 1) showed that female smokers, older smokers and smokers with a higher number of children were more likely to try to quit smoking. In addition, those who reported poorer general health, higher daily cigarette consumption and higher nicotine dependence were more likely to engage in smoking cessation initiatives.

A multivariate logistic regression model between successful smoking cessation and potential predictors was constructed (Table 3). Dependence and adherence were proven to be the statistically significant predictors for successful smoking cessation.

In 176 patients who used prescription medicine, univariate analysis identified dependence, adherence and lower daily cigarette consumption to be correlated with the smoking cessation. However, lower daily cigarette consumption did not prove significant in the multivariate model. In this study, the FTND served as a critical measure for assessing nicotine dependence and showed a robust association with the effectiveness of smoking cessation using the prescribed medications studied. The results of our study also show that treatment adherence to non-NRT pharmacological therapy is essential for smoking cessation, regardless of the medication used (cytisine or varenicline).

Our findings align with prior research indicating that various demographic factors correlate with the likelihood of successfully quitting smoking through pharmacotherapy. These factors include age, gender, level of education, marital status, presence of children and self-assessment of health status (11, 12, 21, 22). However, after adjusting for other variables in the multivariate regression model, only nicotine dependence and adherence to pharmacotherapy protocols were found to be statistically significant predictors of smoking cessation success. A larger sample size would probably confirm or reject the significance of previous sociodemographic variables. This observation is consistent with several studies indicating that FTND scores are an indicator of successful smoking cessation (16,17,18). Indeed, Fagerström's study has shown that higher FTND scores correlate with a lower probability of being abstinent at week 24 (16). Our study confirms this relationship in the context of pharmacotherapeutic interventions. Furthermore, our results highlight the utility of FTND scores in the assessment phase in identifying smokers at increased risk of non-adherence to subsequent treatment sessions (23). Studies on adherence to nicotine replacement therapy (NRT) have shown that adherence doubles the rate of successful smoking cessation (24), and there is a positive correlation between adherence to treatment and tobacco abstinence, with early abstinence experience being a strong driver of adherence (25). Several studies have found a strong relationship between the number of cigarettes smoked and smoking cessation (26, 27), and a longitudinal study of 17,155 persistent smokers who were followed over a six-year period showed that higher daily cigarette consumption, shorter intervals before the first cigarette of the day and regular daily smoking patterns resulted in a lower probability of smoking cessation (13). Regarding prescription medications, Noor et al. showed that lower daily cigarette consumption is associated with a higher likelihood of becoming smoke-free in people undergoing varenicline treatment (28). However, in the multivariate logistic model of our study, this variable was no longer recognized as a significant factor associated with smoking cessation. It is possible that FTND and adherence to treatment might mediate or moderate the relationship between daily cigarette consumption and smoking cessation.

Among other factors investigated, including age, gender, self-perceived general health and number of children, none emerged as a predictive factor for smoking cessation success in our study population, although they were associated with a higher likelihood of attempting smoking cessation. Several other predictors for both trying to quit and successful cessation were described in the literature (29), but none demonstrated statistical significance in our population. There are several possible reasons for this outcome, including complex interactions between variables that could not be fully explored due to a limited sample size.

The pharmacological approach to smoking cessation is widely acknowledged as safe and efficacious, warranting consideration for all individuals committed to quit smoking (9, 19). Notably, varenicline, cytisine treatment and NRT are all effective methods for smoking cessation (30). Although a trial by Courtney et al. failed to demonstrate noninferiority of cytisine compared with varenicline regarding smoking cessation (31), the standard 4-week cytisine treatment was shown to be less effective than the standard 12-week varenicline treatment for smoking cessation in the trial by Orešković et al. (19).

Our study has several notable strengths. While references demonstrate the importance of nicotine dependence for smoking cessation success, the significance of adherence to smoking cessation medications is novel in this context. Our study's key advantage is demonstrating how medication adherence can improve smoking cessation effectiveness in real-world clinical settings. The biggest strength of our research is its practical application in a real family medicine setting. The tools we used to identify candidates for smoking cessation medication can be easily integrated into routine primary care. Additionally, using two different types of smoking cessation medications underscores the thoroughness of our study.

However, our study also has some limitations. First, the small sample size limits the statistical robustness required for an individualized analysis of the efficacy of each medication. Nonetheless, the observed similarity in outcomes between the two medications supports the generalisability of our findings to different pharmacotherapeutic approaches to smoking cessation. There was no control group and no follow-up for smokers who did not receive pharmacotherapy. Furthermore, because we rely on cross-sectional data, we are limited in our ability to establish definitive causal relationships or temporal sequences between smoking cessation success and associated factors. This limitation underscores the need for future longitudinal studies to elucidate the dynamic interplay of these variables over time.

There was no connection with real participant data, which limited the interpretation of results, particularly concerning non-respondents in the context of mental health, previous addiction diseases and socioeconomic status, all of which heavily influence continued smoking according to findings from previous studies (21). Also, the success of quitting smoking can be affected by the condition during or after treatment and by recovering from a serious illness (32, 33). Moreover, it is possible that more motivated FM enrolled patients participated in the study, and this can also be reflected in the population of their patients. While we have not included these variables in our data collection, we want to emphasize their importance and acknowledge their potential impact on the outcomes.

This study highlights the central role of reduced nicotine dependence and higher adherence to pharmacotherapy as robust predictors of smoking cessation success when using pharmacotherapy. This finding enables the identification of potential responders to pharmacotherapeutic interventions and facilitates targeted prescribing and follow-up in primary healthcare. Moving forward, it is imperative to investigate the efficacy and outcomes of targeted pharmacotherapy prescription for smoking cessation through further research efforts. Such investigations will not only improve our understanding of the role of pharmacotherapy in smoking cessation, but will also enable the development of tailored interventions to optimise smoking cessation outcomes more broadly (20).