Effects of different doses of ticagrelor on platelet aggregation and endothelial function in diabetic patients with stable coronary artery disease

We performed this study to observe the effects of different doses of ticagrelor and standard-dose clopidogrel on platelet reactivity and endothelial function in diabetic patients with stable coronary artery disease (CAD). Sixty type 2 diabetic patients were assigned to one-quarter standard-dose ticagrelor, half standard-dose ticagrelor, standard-dose ticagrelor and standard-dose clopidogrel groups. Light transmission aggregometry (LTA) and VerifyNow assay were used to measure platelet function. Endothelial function was assessed by measurement of flow-mediated vasodilation (FMD) and plasma von Willebrand factor (VWF) levels were detected. Enzyme-linked immunosorbent assay (ELISA) examined the Interleukin-8(IL-8) and IL-10. The results suggested that the one-quarter dose (34.0%± 14.7%), half-dose (26.9%± 11.6%) and standard-dose (17.3%± 10.3%) ticagrelor showed lower platelet aggregation rate than clopidogrel (52.8%± 18.3%; <i>P</i> ＜0.0001). PRU values in three ticagrelor groups were lower than that in clopidogrel group (102 (76–184)；75 (33–88)；38 (11–52) versus 194 (138–271) and；<i>P</i> ＜0.0001). FMD levels were higher in ticagrelor groups compared with baseline levels while lower in clopidogrel group after treatment. However, no significant differences were found in the percentage increase in the FMD between ticagrelor groups and clopidogrel group. The levels of VWF after treatment were lower than the baseline levels, but there was no statistically significant difference between ticagrelor group and clopidogrel group after treatment. The concentration of IL-8 and IL-10 were decreased in patients with half and standard-dose ticagrelor group. In conclusion, one-quarter standard-dose ticagrelor produced similar inhibitory effects on platelet aggregation as standard-dose clopidogrel in diabetic patients with stable CAD. The half standard-dose ticagrelor had a similar inhibitory effect on platelet inhibition as standard-dose ticagrelor, which was stronger than that of clopidogrel. Moreover, the half-dose ticagrelor had equal protection of endothelial function and inhibition of inflammatory factor as standard-dose ticagrelor.

本研究旨在观察不同剂量替格瑞洛与标准剂量氯吡格雷对稳定型冠状动脉疾病（stable coronary artery disease, CAD）合并糖尿病患者的血小板反应性与内皮功能的影响。本研究纳入60例2型糖尿病患者，将其随机分配至四分之一标准剂量替格瑞洛组、半标准剂量替格瑞洛组、标准剂量替格瑞洛组及标准剂量氯吡格雷组。采用光透射聚集试验（light transmission aggregometry, LTA）与VerifyNow检测法测定血小板功能；通过血流介导的血管舒张功能（flow-mediated vasodilation, FMD）评估内皮功能，并检测血浆血管性血友病因子（von Willebrand factor, VWF）水平；采用酶联免疫吸附试验（enzyme-linked immunosorbent assay, ELISA）检测白细胞介素8（Interleukin-8, IL-8）与白细胞介素10（IL-10）的浓度。结果显示：四分之一剂量组（34.0%±14.7%）、半剂量组（26.9%±11.6%）与标准剂量组（17.3%±10.3%）替格瑞洛的血小板聚集率均低于氯吡格雷组（52.8%±18.3%；P<0.0001）；三组替格瑞洛组的血小板反应单位（PRU）值均低于氯吡格雷组（分别为102（76–184）、75（33–88）、38（11–52），氯吡格雷组为194（138–271）；均P<0.0001）。治疗后，替格瑞洛组的FMD水平较基线升高，而氯吡格雷组的FMD水平较基线降低，但两组间FMD增幅无统计学差异。治疗后各组的血浆VWF水平均较基线降低，但替格瑞洛组与氯吡格雷组间的VWF水平差异无统计学意义。半剂量与标准剂量替格瑞洛组患者的IL-8与IL-10浓度均有所下降。综上，在合并稳定型CAD的糖尿病患者中，四分之一标准剂量替格瑞洛对血小板聚集的抑制效果与标准剂量氯吡格雷相当；半标准剂量替格瑞洛的血小板抑制效果与标准剂量替格瑞洛相近，且优于氯吡格雷。此外，半剂量替格瑞洛在保护内皮功能与抑制炎症因子方面与标准剂量替格瑞洛效果相当。