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不同剂量替格瑞洛对稳定型冠心病合并糖尿病患者血小板聚集和血管内皮功能的影响。

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

机构信息

a Cardiovascular Department , the First Affiliated Hospital of Harbin Medical University , Harbin , Heilongjiang , P.R. China.

b Cardiovascular Department , Harbin Red Cross Central Hospital , Harbin , Heilongjiang , P.R. China.

出版信息

Platelets. 2019;30(6):752-761. doi: 10.1080/09537104.2018.1513479. Epub 2018 Sep 25.

DOI:10.1080/09537104.2018.1513479
PMID:30252571
Abstract

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%;  <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; <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.

摘要

我们进行这项研究旨在观察不同剂量替格瑞洛和标准剂量氯吡格雷对稳定型冠心病(CAD)糖尿病患者血小板反应性和内皮功能的影响。将 60 例 2 型糖尿病患者分为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和标准剂量氯吡格雷组。采用光透射聚集法(LTA)和 VerifyNow 检测血小板功能。通过测量血流介导的血管扩张(FMD)评估内皮功能,并检测血浆血管性血友病因子(VWF)水平。酶联免疫吸附试验(ELISA)检测白细胞介素-8(IL-8)和白细胞介素-10(IL-10)。结果表明,与氯吡格雷(52.8%±18.3%)相比,四分之一剂量(34.0%±14.7%)、半剂量(26.9%±11.6%)和标准剂量(17.3%±10.3%)替格瑞洛的血小板聚集率更低(<0.0001)。三个替格瑞洛组的 PRU 值均低于氯吡格雷组(102(76-184);75(33-88);38(11-52)与 194(138-271);<0.0001)。替格瑞洛组治疗后的 FMD 水平较基线水平升高,而氯吡格雷组治疗后则降低。然而,替格瑞洛组与氯吡格雷组的 FMD 升高百分比之间无显著差异。治疗后 VWF 水平低于基线水平,但替格瑞洛组与氯吡格雷组之间无统计学差异。半剂量和标准剂量替格瑞洛组患者的 IL-8 和 IL-10 浓度降低。结论:与稳定型 CAD 糖尿病患者的标准剂量氯吡格雷相比,四分之一标准剂量替格瑞洛对血小板聚集的抑制作用相似。半标准剂量替格瑞洛对血小板抑制作用与标准剂量替格瑞洛相似,且强于氯吡格雷。此外,半剂量替格瑞洛对内皮功能和炎症因子的抑制作用与标准剂量替格瑞洛相当。

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