Cilostazol Decreases Endothelin-1 Level in Patients with an Acute Coronary Syndrome: A Prospective Study

Abstract

Objectives: This study aimed to determine whether the plasma markers of endothelial dysfunction could be influenced by cilostazol in patients with Acute Coronary Syndrome (ACS).Background: Endothelial dysfunction is associated with an imbalance between Nitric Oxide (NO) and Endothelin-1 (ET-1), which has been found to be involved in the pathogenesis of ACS. Cilostazol is a selective inhibitor of phosphodiesterase type III that inhibits platelet aggregation. The superior clinical benefit of cilostazol over aspirin suggests that the drug has non-plateletdirected properties. Animal and in vitro models suggested that the "pleiotropic" properties of cilostazol may be related to its "endothelial protection" effects. However, whether cilostazol can influence plasma markers of endothelial dysfunction in real-world patients is still unknown.Methods: This prospective study was conducted from February 2016 to July 2016 and enrolled consecutive 143 patients with ACS receiving primary Percutaneous Coronary Intervention (PCI) receiving either cilostazol (N = 61) or aspirin (N =82). Plasma levels of ET-1, NO and High-Sensitivity C-Reactive Protein (hs-CRP) were measured. Major Adverse Cardiovascular Events (MACEs), defined as cardiac death, recurrent Myocardial Infarction (MI), restenosis, Target Vessel Revascularization (TVR), or stroke, were assessed during the 6-month follow-up period. Results:The two groups had similar clinical, angiographic, and procedural characteristics at baseline. The baseline plasma levels of NO and ET-1 were similar in the patients of the two groups. NO concentration was similar in patients receiving cilostazol or aspirin (85.30 ± 30.46 vs. 84.57 ± 29.86 μmol/L, P =0.89). Meanwhile, patients receiving cilostazol had significantly lower plasma level of ET-1 than patients receiving aspirin (110.4 ± 96.94 vs. 141.3 ± 82.49 pg/ mg, P=0.049). In addition, ET-1 was positively correlated with hs-CRP with marginal statistical significance (p < 0.001). Conclusion:Cilostazol decreases ET-1concentration in ACS patients compared with aspirin. No statistically significant difference was observed in MACEs between the two groups. This pilot study provides scientific basis to call for a large-scale prospective study with long-term follow-up to further confirm those findings.