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替格瑞洛联合或不联合阿司匹林对血小板反应性和凝血激活的影响差异:一项在健康志愿者中的随机试验。

Differential Effects of Ticagrelor With or Without Aspirin on Platelet Reactivity and Coagulation Activation: A Randomized Trial in Healthy Volunteers.

机构信息

Department of Medicine I, Medical University of Vienna, Vienna, Austria.

Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of Vienna, Vienna, Austria.

出版信息

Clin Pharmacol Ther. 2020 Feb;107(2):415-422. doi: 10.1002/cpt.1616. Epub 2019 Sep 28.

Abstract

Dual antiplatelet therapy (DAPT) is standard in acute coronary heart disease but confers a bleeding risk. To compare the effects of ticagrelor-monotherapy with ticagrelor-based DAPT on hemostatic system activation, we conducted a randomized controlled trial in 44 volunteers using a loading-dose regimen and measured platelet-aggregometry triggered by adenosine diphosphate (multiple electrode aggregometry (MEA)-ADP) and arachidonic acid (MEA-AA), the vasodilator-stimulated phosphoprotein (VASP), prothrombin fragment 1.2 (f1.2), and d-Dimer. Ticagrelor-based DAPT and ticagrelor-monotherapy significantly decreased MEA-ADP (Δmean: -51.4 (-56.9; -45.8) and -46.2 (-51.7; -40.7)) and VASP (Δmean: -70.3 (-76.2; -64.4) and -69.6 (-75.5; -63.7)) at 2 hours and over 24 hours. MEA-AA was reduced significantly by both treatments (Δmean: -72.9 (-80.6; -65.3) and -25.7 (-33.3; -18.0)) at 2 hours, and stronger by ticagrelor-based DAPT over 24 hours. Both treatments decreased f1.2 (geometric mean ratio (GMR): 0.92 (0.84; 1.01) and 0.88 (0.80; 0.96)) and d-Dimer (GMR: 0.89 (0.86; 0.92) and 0.91 (0.88; 0.94)) at 2 hours and d-Dimer over 24 hours. Ticagrelor-monotherapy and ticagrelor-based DAPT comparably affect hemostatic system activation.

摘要

双联抗血小板治疗(DAPT)是急性冠状动脉心脏病的标准治疗方法,但会增加出血风险。为了比较替格瑞洛单药治疗与替格瑞洛为基础的 DAPT 对止血系统激活的影响,我们在 44 名志愿者中进行了一项随机对照试验,使用负荷剂量方案,并通过二磷酸腺苷(MEA-ADP)和花生四烯酸(MEA-AA)、血管扩张刺激磷蛋白(VASP)、凝血酶原片段 1.2(f1.2)和 D-二聚体测量血小板聚集诱导试验(MEA)。替格瑞洛为基础的 DAPT 和替格瑞洛单药治疗均能显著降低 MEA-ADP(Δ均值:-51.4(-56.9;-45.8)和-46.2(-51.7;-40.7))和 VASP(Δ均值:-70.3(-76.2;-64.4)和-69.6(-75.5;-63.7))在 2 小时和 24 小时以上。两种治疗方法均能显著降低 MEA-AA(Δ均值:-72.9(-80.6;-65.3)和-25.7(-33.3;-18.0))在 2 小时内,替格瑞洛为基础的 DAPT 在 24 小时以上的效果更强。两种治疗方法均能降低 f1.2(几何均数比(GMR):0.92(0.84;1.01)和 0.88(0.80;0.96))和 D-二聚体(GMR:0.89(0.86;0.92)和 0.91(0.88;0.94))在 2 小时内和 D-二聚体在 24 小时内。替格瑞洛单药治疗和替格瑞洛为基础的 DAPT 对止血系统的激活有相似的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3ef/7006887/88a2d8cc048b/CPT-107-415-g001.jpg

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