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替格瑞洛能改善血管内皮功能吗?

Does Ticagrelor Improve Endothelial Function?

机构信息

1 Department of Cardiology, Patras University Hospital, Patras, Greece.

2 Second Department of Cardiology, Attikon University Hospital, National and Kapodistrian University of Athens Medical School, Athens, Greece.

出版信息

J Cardiovasc Pharmacol Ther. 2019 Jan;24(1):11-17. doi: 10.1177/1074248418786936. Epub 2018 Jul 10.

Abstract

Ticagrelor is a P2Y receptor antagonist with proven clinical benefit in patients with acute coronary syndrome. Apart from its principal antiplatelet action, pleiotropic effects have been implicated in the clinical profile of ticagrelor, including a potentially beneficial impact on endothelial function. In light of the common presence and prognostic value of endothelial dysfunction in patients with coronary artery disease, several clinical studies have investigated the postulated effect of ticagrelor on endothelial function, yielding conflicting results. Limitations of the relevant studies as well as substantial differences in patient population, study design, and methods may account for these controversial findings. Most of these studies, however, support a beneficial impact of ticagrelor on endothelial function, which seems to be significant in the higher risk patients. In order to elucidate this effect, further research efforts should aim to clarify how quickly does endothelial function respond to ticagrelor, how sustained this response is during the dosing intervals and in the long term, which mechanisms are implicated, and whether this pleiotropic action is clinically significant. Future studies should include larger and diverse populations of patients, assess endothelial function at several time points after treatment initiation, and use multiple methods of endothelial function measurement, while implementing strict methodology. Nevertheless, the extent of the clinical benefit of ticagrelor attributable to actions beyond its potent and consistent antiplatelet effect remains uncertain.

摘要

替格瑞洛是一种 P2Y 受体拮抗剂,已被证明可使急性冠脉综合征患者获益。除了主要的抗血小板作用外,替格瑞洛的多种作用机制也与其临床特征相关,包括对内皮功能可能有益的影响。鉴于内皮功能障碍在冠心病患者中普遍存在且具有预后价值,多项临床研究探讨了替格瑞洛对内皮功能的推测作用,但结果存在争议。相关研究的局限性以及患者人群、研究设计和方法的显著差异可能是这些有争议发现的原因。然而,这些研究大多支持替格瑞洛对内皮功能具有有益影响,这种影响在高危患者中似乎更为显著。为了阐明这种作用,进一步的研究工作应旨在阐明内皮功能对替格瑞洛的反应速度有多快,在给药间隔和长期内这种反应的持续时间,涉及哪些机制,以及这种多效性作用是否具有临床意义。未来的研究应包括更多样化的患者人群,在治疗开始后多个时间点评估内皮功能,并使用多种内皮功能测量方法,同时实施严格的方法学。然而,替格瑞洛除了强效且持续的抗血小板作用之外,其对临床获益的影响程度仍不确定。

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