Impact of statin and ezetimibe for the prevention of stroke in patients with atrial fibrillation

Abstract Objective Statin is strongly recommended for the primary and secondary prevention of cardiovascular disease (CVD). However, statin therapy in patients with atrial fibrillation (AF) remains controversial for the prevention of ischemic stroke. Ezetimibe emerged as the potent additive or synergistic drug for the management of CVD with reduced adverse effects associated with statin therapy. This study is aimed to evaluate impact of statin and ezetimibe for the risk reduction of stroke in patients with AF. Materials and Methods We constructed a retrospective cohort of patients with AF (n=2,062) from a registry of patients with arrhythmia (n=6,817) between 2010 and 2023 in Clinical Data Warehouse established by K-Health National Medical Care Service. Diagnoses were defined based on ICD-10 codes. Drug prescriptions were defined based on ATC codes. Primary end-point was the time to the first event of newly onset ischemic stroke. Secondary end-point was defined as the composite clinical outcomes of death, stroke, and hospitalization due to heart failure. Time-dependent Cox hazard models were used to analyze factors influencing the occurrence of stroke. propensity score matching was utilized for the analysis of clinical outcomes. Results Independent risk factors for stroke in patients with AF were the previous history of stroke (HR 9.49, 95% CI 7.97-11.29), peripheral artery disease (HR 1.83, 95% CI 1.28-2.61), age (HR 1.02, 95% CI 1.01-1.03), use of statin (HR 0.98, 95% CI 0.97-0.98 and use of anticoagulants (HR 0.29, 95% CI 0.17-0.49). Statin therapy significantly delayed time to the first event of ischemic stroke compared to no statin therapy (342.6 ± 58.9 days, p0.001; 894.9 ± 110.5 vs. 1,237.5 ± 122.3 days, p0.001). Combination therapy of statin and ezetimibe significantly delayed time to the first event of ischemic stroke compared to statin mono-therapy (643.4 ± 50.1days, p0.001; 1,237.5 ± 122.3 vs. 1,880.9 ± 278.5 days, p0.001). Composite clinical outcomes at 1-year was significantly reduced with use of statin (13.3% vs. 24.9%, HR 0.62, 95% CI 0.48-0.73) compared with no statin therapy. Combination therapy of statin and ezetimibe had similar risk reduction of composite clinical outcomes compared with statin mono-therapy. Conclusion Statin therapy significantly delayed time to new-onset stroke in patients with AF. Furthermore, ezetimibe add-on to statin had additive effects for delaying time to stroke. Statin or statin/ezetimibe therapy should be considered as the primary prevention for stroke in patients with AF.