Patient-Level Determinants Outweigh Pharmacotherapy Choice in Smoking Cessation: Evidence from a Real-World Study in...

Background/Objectives: The relative contribution of pharmacotherapy versus patient-level factors to smoking cessation success remains unclear, particularly in real-world settings where access to first-line treatments such as varenicline is limited. This study aimed to compare the effectiveness of commonly used pharmacotherapies and to identify independent predictors of cessation in a primary care setting in Turkey. Methods: In this prospective observational study, 487 adult smokers attending a smoking cessation clinic in Istanbul, Turkey, were included. Participants received cytisine (n = 243), bupropion (n = 130), nicotine replacement therapy (NRT) (n = 8), bupropion plus NRT (n = 38), or a non-pharmacological intervention consisting of structured behavioral counseling without pharmacotherapy (n = 68), based on clinical judgment and patient preference. Baseline sociodemographic characteristics, smoking history, and nicotine dependence (Fagerström Test for Nicotine Dependence, FTND) were recorded. Smoking cessation at 3 months was assessed via telephone follow-up. Multivariable logistic regression was used to identify independent predictors of cessation. Results: The overall 3-month cessation rate was 32.2% (138/429). Bupropion plus NRT combination therapy was associated with significantly higher odds of cessation than cytisine (aOR = 2.36, 95% CI: 1.10-5.08, p = 0.028), while bupropion, NRT, and non-pharmacological treatment did not differ significantly from cytisine; given the very small NRT subgroup (n = 8), this estimate should be interpreted cautiously. Among patient-level factors, higher educational level (aOR = 1.38, 95% CI: 1.02-1.85, p = 0.035), a prior quit attempt (aOR = 2.14, 95% CI: 1.14-4.00, p = 0.018), and a longer duration of prior abstinence (aOR = 1.01 per month, 95% CI: 1.00-1.02, p = 0.034) were independently associated with higher odds of cessation. Age, sex, employment status, number of previous quit attempts, and FTND score were not significant predictors. These findings should be interpreted with caution given the non-randomized design, short follow-up, and self-reported, biochemically unverified outcome ascertainment described below. Conclusions: In this real-world cohort from Turkey, bupropion plus NRT combination therapy, along with several patient-level factors, was independently associated with 3-month smoking cessation. These findings suggest a potential benefit of combination pharmacotherapy that warrants confirmation in larger, adequately powered studies, and highlight the continued importance of individualized, behaviorally informed cessation strategies, particularly in settings with constrained access to first-line treatments such as varenicline.