Attempted before, achieved now: Cytisinicline in a structured smoking cessation program

Abstract Introduction Smoking cessation is essential for secondary prevention after cardiovascular events. Although several behavioural strategies and pharmacological therapies are available, their effectiveness remains variable, and the optimal approach to support cessation is still uncertain. Cytisinicline is a promising agent, but evidence in high-risk cardiac populations is limited. Purpose To evaluate the efficacy of a structured smoking cessation program incorporating cytisinicline in patients undergoing cardiac rehabilitation. Methods This single-center prospective study included consecutive cardiac rehabilitation patients who voluntarily entered a structured smoking cessation program between 2024 and 2025. Nicotine dependence was assessed using the Fagerström Test. All patients received cytisinicline with or without concomitant nicotine replacement therapy for 25 days and were followed for a mean of 6 months, with medication adherence and smoking status evaluated at baseline and during follow-up. Results A total of 24 patients were enrolled in the smoking cessation program (mean age 56 ± 2 years; 21 88% male). Coronary artery disease was present in 71% (multivessel 13%); peripheral artery disease in 8%; hypertension and dyslipidemia occurred in 54% each; diabetes in 29%. Mean smoking duration was 38 ± 2 years and mean smoking burden was 41 ± 3 pack-years. Severe nicotine dependence was identified in 9 patients (38%) and 14 (58%) had previously attempted smoking cessation. Smoking duration was significantly associated with ischemic heart disease (38 vs 29 years, p=0.03) and peripheral artery disease (51 ± 1.4 vs 36 ± 11 years, p=0.001). In multivariable analysis, smoking duration remained independently associated with coronary artery disease, with a 14.8% increase in the odds per additional smoking year (OR 1.148; p=0.043), after adjustment for hypertension and diabetes. All patients underwent a 25-day regimen of cytisinicline and nicotine replacement therapy, except one who discontinued early due to gastrointestinal side effects. By the end of treatment, 12 (50%) patients achieved complete cessation, 7 (29%) reduced tobacco use and 5 (21%) continued smoking. Over a 7 ± 1-month follow-up, 3 of the 12 quitters (25%) relapsed, while all 7 patients who reduced consumption maintained this reduction. No significant associations were observed between cessation success and smoking duration, burden, or nicotine dependence. Compared with cardiac rehabilitation patients not enrolled in the structured cessation program (~10% cessation), this program achieved a markedly higher cessation rate of 37%. Conclusion In our cohort, cytisinicline was well tolerated and associated with improved cessation outcomes in cardiac rehabilitation patients. These findings suggest that structured smoking cessation programs may substantially improve abstinence rates in high-risk cardiovascular patients.