Cilostazol improves endothelial function in acute cerebral ischemia patients: a double-blind placebo controlled trial with flow-mediated dilation technique

Abstract

BackgroundIn order to evaluate the impact of cilostazol on endothelial function, we compared the changes of flow-mediated dilation (FMD) between aspirin and cilostazol groups in patients with acute cerebral ischemia.MethodsPatients presenting with acute cerebral ischemic events were randomly assigned into aspirin (n = 40) or cilostazol (n = 40) group in a double-blinded manner. FMD was measured at baseline (T0) and 90 days (T1). We measured L-arginine at baseline (a precursor of biologically active nitric oxides). Serious and non-serious adverse events were described.ResultsDespite no difference in the baseline FMD values (p = 0.363), there was a significant increase of FMD values in cilostazol group (7.9 ± 2.4 to 8.9 ± 2.3%, p = 0.001) and not in aspirin group (8.5 ± 2.6 to 9.3 ± 2.8%, p = 0.108). In the multiple regression analysis performed in cilostazol group, serum L–arginine levels were inversely correlated with FMD at T1 (ß = −0.050, SE: 0.012, p < 0.001) with age, total cholesterol levels, and C-reactive protein as confounders. While T0 FMD values in both aspirin and cilostazol groups did not show any correlation with serum L-arginine levels, the correlation is restored in the cilostazol group at T1 (r = 0.467, p = 0.007), while such is not shown in the aspirin group. There was no difference of serious adverse events between the two groups (p = 0.235). Adverse events were more common in the cilostazol group (35/40 vs. 25/40, p = 0.010), due to frequent headaches (14/40 vs. 3/30, p = 0.003) which was well tolerated.ConclusionCilostazol improved endothelial function in acute cerebral ischemia patients. It also restored an inverse correlation between 3-month FMD and baseline L-arginine levels.Trial registration NCT03116269, 04/12/2017, retrospectively registered.Electronic supplementary materialThe online version of this article (10.1186/s12883-017-0950-y) contains supplementary material, which is available to authorized users.

Cilostazol for Secondary Prevention of Stroke and Cognitive Decline

“…The time to randomization after diagnosis was <2 weeks in 8 (n=1940), 12 , 14 , 15 , 19 – 21 , 23 , 24 between 2 weeks and 6 months in 5 (n=2123), 13 , 18 , 25 – 27 and 6 months or later in 6 trials (n=6406; including the one trial in cognitive decline/dementia) 10 , 11 , 16 , 17 , 22 , 28 and was not stated in the other trial in cognitive decline. 9 The duration of trial treatment was 4 weeks in 3 (n=344), 19 , 20 , 28 10 weeks in 1 (n=57), 11 4 months in 4 (n=1236), 12 , 20 , 22 , 23 6 to 8 months in 5 (n=753; including both trials in cognitive decline/dementia), 9 , 10 , 14 , 15 , 18 12 months in 1 (n=68), 27 and between 12 months and 5 years in 6 trials (n=8034).…”

Cilostazol for secondary stroke prevention: systematic review and meta-analysis

“…We included 18 randomised trials comprising 11 429 patients in the ITT population [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] (tables 1 and 2). Nine studies were conducted in Japan, four in Korea, two in China, two in multiple East Asian countries and one in the UK.…”

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

“…Cilostazol is widely used in patients with coronary artery disease after receiving PCI to reduce the risk of thrombotic events. The beneficial effects of cilostazol appear to extend beyond its obvious antiplatelet effects, and have been attributed to its reduction of in-stent and in-segment restenosis [28][29][30], protective effect against ischemia-reperfusion injury [31] and improvement of endothelial function [32,33]. A recent research suggested that cilostazol could inhibit apoptosis in some circumstances to protect cell viability [34] indicating that cilostazol might protect endothelia in a similar way.…”