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

机译:Ticagrelor作为心脏患者对阿司匹林无敏感的替代抗血小板治疗

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摘要

Background and Objectives: 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. Materials and Methods: 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. Results: 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. Conclusions: Our results suggest that ticagrelor is a promising alternative therapy for patients who are non-sensitive to ASA.
机译:背景和目标:阿司匹林(乙酰山酸-ASA)是向冠状动脉疾病(CAD)患者提供的一线抗血小板疗法。然而,已经证明,这些患者中的20-30%对其ASA治疗是不敏感的。 ASA非敏感性是一种现象,其中低剂量ASA(81-325mg)没有完全抑制花生酸诱导的血小板聚集,使患者患有不良心脏血栓形成事件的风险。 TiCagrelor是一种P2Y12受体抑制剂和替代抗血小板,已被批准降低中风,心肌梗死和整体心血管相关死亡的风险。在这项研究中,我们旨在鉴定ASA非敏感患者并评估它们是否对TicagreloR敏感。材料和方法:对于这项试验研究,招募了38名CAD患者服用81毫克ASA。从分离每个样品的每位患者和血小板富血浆(PRP)中收集血样。使用0.5mg / ml花生酸作为血小板激动剂,用于测定每位患者的基线ASA敏感性的光传动聚合物(LTA)。活化后≥20%的血小板聚集患者被认为是非敏感性的。然后将来自所有患者的新鲜PRP样品掺入TicagreloR的临床用量(3μm-大约相当于180mg ticagreloR的装载剂量)。使用LTA和5μMADP作为血小板激动剂测定敏感性。最大血小板聚集的患者被认为是Ticaglelor非敏感性。结果:38名CAD患者服用81毫克ASA,32%(12/38)对其81毫克ASA治疗不敏感。所有38名募集患者(100%)对TicagreloLor exvivo敏感。总之,我们能够使用LTA鉴定ASA非敏感性,并确定ASA非敏感患者对TiCagrelor敏感。结论:我们的研究结果表明,Ticagrelelor对于对ASA的患者来说是一个有前途的替代疗法。

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