P1929A randomized controlled trial evaluating outcome impact of cilostazol in patients with coronary artery disease and at a high risk of cardiovascular disease

Abstract

Abstract Background We and others have previously found that cilostazol has a favorable effect on glucose and lipid homeostasis, endothelial function, anti-atherosclerosis, and vasculo-angiogenesis. However, it is poorly understood that if this compound can provide better clinical outcome. Purpose This study investigated the outcome effect of cilostazol in patients with coronary artery disease (CAD) or at a high risk of cardiovascular (CV) disease. Methods We conducted a randomized, double-blind, placebo controlled trial involving 266 patients to receive cilostazol 200 mg/day (n=134) or dummy placebo (n=132). The primary endpoint was a composite of CV death, non-fatal myocardial infarct, non-fatal stroke, hospitalization for congestive heart failure or unplanned coronary revascularization. Pre-specified secondary endpoints include the composite major coronary event (MCE) and major adverse CV and cerebrovascular event (MACCE) on long-term follow-up. The mean duration of follow-up was 2.9 years. Results Relative to placebo, cilostazol treatment had a borderline effect on risk reduction in the primary endpoint (hazard ratio [HR], 0.67; 95% confidence interval (CI), 0.34–1.33), whereas the beneficial effect in favor of cilostazol was significant in patients with diabetes mellitus or a history of percutaneous coronary intervention (P for interaction, 0.02 and 0.06, respectively). Use of cilostazol, but not placebo, significantly reduced the risk of the MCE (HR, 0.38; 95% CI, 0.17–0.86) and MACCE (HR, 0.47; 95% CI, 0.23–0.96). A significantly lower risk of angina pectoris (HR, 0.38; 95% CI, 0.17–0.86) and unplanned revascularization (HR, 0.13; 95% CI, 0.02–1.09) was also observed in the cilostazol group. After multi-variable adjustment, cilostazol treatment independently predicted a lower risk of the MCE and MACCE. Conclusions Cilostazol treatment significantly reduced the risk of CV events in patients with CAD or at a high risk of CV disease. Acknowledgement/Funding MOST 106-2314-B-006-044, MOHW106-TDU-B-211-113003, MOHW107-TDU-B-211-113003, and MOST107-2314-B-006-076-MY2