Long-Term Comparison of Cilostazol versus Clopidogrel in Secondary Prevention of Noncardioembolic Ischemic Stroke

Abstract Background Cilostazol is a widely used antiplatelet drug for secondary stroke prevention in Asia, but its comparison with clopidogrel, another commonly used antiplatelet drug, is not well understood. This study aims to investigate the effectiveness and safety of cilostazol compared to clopidogrel for the secondary prevention of noncardioembolic ischemic stroke. Methods A retrospective comparative effectiveness research analysis was conducted using 1:1 propensity-matched data from insured individuals between Jan 1, 2012, and Dec 31, 2019. The study used administrative claims data in Health Insurance and Review Assessment in Korea. Patients with diagnosis codes for ischemic stroke without atrial fibrillation, heart failure, valvular diseases, and myocardial infarction were included and divided into two groups, those receiving cilostazol and those receiving clopidogrel. The primary outcome was a recurrent ischemic stroke. Secondary outcomes included all-cause death, myocardial infarction, hemorrhagic stroke, and a composite of these outcomes. The safety outcome was major gastrointestinal bleeding. Results A total of 4754 patients were included in the propensity-matched population, with a median age of 67 years, 3080 (40.7%) were male, and 4480 (59.3%) were female. The study found no statistically significant difference in recurrent ischemic stroke (cilostazol group vs clopidogrel group, 2.7% vs 3.2%; 95% CI, 0.62-1.21), the composite outcome of recurrent ischemic stroke, all-cause death, myocardial infarction, and hemorrhagic stroke (5.1% vs 5.5%; 95% CI 0.75-1.22), and major gastrointestinal bleeding (1.3% vs 1.5%; 95% CI 0.57-1.47) between cilostazol and clopidogrel use patients. In subgroup analysis, cilostazol was associated with a lower incidence of recurrent ischemic stroke compared to clopidogrel in hypertensive patients (2.5% vs 3.9%; interaction P = 0.41). Conclusions This real-world, comparative effectiveness research study suggests that cilostazol is effective and safe for noncardioembolic ischemic stroke and may be associated with better effectiveness in hypertensive patients compared to clopidogrel over an 8-year period.