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替格瑞洛作为阿司匹林不耐受心脏病患者的替代抗血小板治疗药物

Ticagrelor as an Alternative Antiplatelet Therapy in Cardiac Patients Non-Sensitive to Aspirin.

作者信息

Khan Hamzah, Gallant Reid, Jain Shubha, Al-Omran Mohammed, De Mestral Charles, Greco Elisa, Wheatcroft Mark, Alazonni Ashraf, Abdin Rawand, Rand Margaret L, Ni Heyu, Qadura Mohammad

机构信息

Division of Vascular Surgery, St. Michael's Hospital, Toronto, ON M5B 1W8, Canada.

Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, ON M5B 1W8, Canada.

出版信息

Medicina (Kaunas). 2020 Oct 2;56(10):519. doi: 10.3390/medicina56100519.

Abstract

Aspirin (acetylsalicylic acid-ASA) is a first-line antiplatelet therapy provided to patients with coronary artery disease (CAD). However, it has been demonstrated that 20-30% of these patients are non-sensitive to their ASA therapy. ASA non-sensitivity is a phenomenon where low-dose ASA (81-325 mg) does not completely inhibit arachidonic-acid-induced platelet aggregation, putting patients at risk of adverse cardio-thrombotic events. Ticagrelor is a P2Y12 receptor inhibitor and alternative antiplatelet that has been approved to reduce the risk of stroke, myocardial infarction, and overall cardiovascular-related death. In this study, we aimed to identify ASA non-sensitive patients and evaluate if they would be sensitive to ticagrelor. For this pilot study, thirty-eight patients with CAD taking 81 mg ASA were recruited. Blood samples were collected from each patient and platelet rich plasma (PRP) from each sample was isolated. Light-transmission aggregometry (LTA) was used to determine baseline ASA sensitivity in each patient using 0.5 mg/mL arachidonic acid as a platelet agonist. Patients with ≥20% maximal platelet aggregation after activation were considered ASA non-sensitive. Fresh PRP samples from all patients were then spiked with a clinical dosage of ticagrelor (3 μM-approximately equivalent to a loading dose of 180 mg ticagrelor). Sensitivity was determined using LTA and 5 μM ADP as a platelet agonist. Patients with ≥46% maximal platelet aggregation were considered ticagrelor non-sensitive. Of the 38 CAD patients taking 81 mg ASA, 32% (12/38) were non-sensitive to their 81 mg ASA therapy. All 38 of the recruited patients (100%) were sensitive to ticagrelor ex vivo. In conclusion, we were able to identify ASA non-sensitivity using LTA and determine that ASA non-sensitive patients were sensitive to ticagrelor. Our results suggest that ticagrelor is a promising alternative therapy for patients who are non-sensitive to ASA.

摘要

阿司匹林(乙酰水杨酸-ASA)是为冠状动脉疾病(CAD)患者提供的一线抗血小板治疗药物。然而,已经证明这些患者中有20%-30%对其ASA治疗不敏感。ASA不敏感是一种低剂量ASA(81-325毫克)不能完全抑制花生四烯酸诱导的血小板聚集的现象,使患者面临不良心脏血栓事件的风险。替格瑞洛是一种P2Y12受体抑制剂和替代抗血小板药物,已被批准用于降低中风、心肌梗死和总体心血管相关死亡的风险。在本研究中,我们旨在识别ASA不敏感患者,并评估他们是否对替格瑞洛敏感。对于这项初步研究,招募了38名服用81毫克ASA的CAD患者。从每位患者采集血样,并从每个样本中分离出富含血小板的血浆(PRP)。使用透光聚集法(LTA),以0.5毫克/毫升花生四烯酸作为血小板激动剂,测定每位患者的基线ASA敏感性。激活后最大血小板聚集率≥20%的患者被认为对ASA不敏感。然后,将所有患者的新鲜PRP样本加入临床剂量的替格瑞洛(3微摩尔-大约相当于180毫克替格瑞洛的负荷剂量)。使用LTA并以5微摩尔ADP作为血小板激动剂来确定敏感性。最大血小板聚集率≥46%的患者被认为对替格瑞洛不敏感。在38名服用81毫克ASA的CAD患者中,32%(12/38)对其81毫克ASA治疗不敏感。所有38名招募的患者(100%)在体外对替格瑞洛敏感。总之,我们能够使用LTA识别ASA不敏感,并确定ASA不敏感患者对替格瑞洛敏感。我们的结果表明,替格瑞洛对于对ASA不敏感的患者是一种有前景的替代治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1516/7600331/f740f5d0d8b8/medicina-56-00519-g001.jpg

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