Moschonas Iraklis C, Tselepis Alexandros D
1 Atherothrombosis Research Centre/Laboratory of Biochemistry, Department of Chemistry, University of Ioannina, Ioannina, Greece.
J Cardiovasc Pharmacol Ther. 2017 Mar;22(2):133-141. doi: 10.1177/1074248416662347. Epub 2016 Aug 11.
Type 2 diabetes mellitus (T2DM) is a progressive and multifactorial metabolic disease mainly characterized by hyperglycemia and insulin resistance. Abnormal platelet reactivity associated with an increased risk of cardiovascular disease (CVD) is also a feature characteristic of patients with T2DM. Dual antiplatelet therapy consisting of aspirin and an adenosine diphosphate platelet P2Y receptor antagonist, such as clopidogrel, represents the standard antithrombotic regimen for the secondary prevention of CVD risk in T2DM. However, a high proportion of patients with T2DM exhibit high on-treatment platelet reactivity to aspirin and/or clopidogrel, associated with a greater risk of adverse cardiovascular events compared with nondiabetic patients. Consequently, novel antiplatelet therapeutic approaches may be required in order to avoid such events. Vorapaxar is a novel antiplatelet agent that targets the platelet protease-activated receptor 1 and inhibits thrombin-induced platelet activation. Vorapaxar has been studied in 2 phase III clinical trials and has been approved for use in the secondary prevention of atherothrombotic events in patients with a previous myocardial infarction (MI) or peripheral arterial disease. New data from the Thrombin-Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2°P)-TIMI 50 trial MI cohort demonstrate that the subgroup of patients with T2DM exhibits increased benefit from vorapaxar use compared with non-T2DM patients. The aim of the present work is to critically review the current knowledge concerning vorapaxar use in patients with T2DM as well as to discuss the possible mechanism(s) underlying vorapaxar's beneficial effect in T2DM.
2型糖尿病（T2DM）是一种进行性多因素代谢疾病，主要特征为高血糖和胰岛素抵抗。与心血管疾病（CVD）风险增加相关的血小板反应性异常也是T2DM患者的一个特征。由阿司匹林和二磷酸腺苷血小板P2Y受体拮抗剂（如氯吡格雷）组成的双重抗血小板治疗是T2DM患者心血管疾病风险二级预防的标准抗栓方案。然而，与非糖尿病患者相比，很大一部分T2DM患者对阿司匹林和/或氯吡格雷的治疗期血小板反应性较高，不良心血管事件风险更大。因此，可能需要新的抗血小板治疗方法来避免此类事件。沃拉帕沙是一种新型抗血小板药物，靶向血小板蛋白酶激活受体1并抑制凝血酶诱导的血小板活化。沃拉帕沙已在两项III期临床试验中进行了研究，并已获批用于既往有心肌梗死（MI）或外周动脉疾病患者的动脉粥样硬化血栓形成事件的二级预防。来自动脉粥样硬化血栓形成缺血事件二级预防中的凝血酶受体拮抗剂（TRA 2°P）-TIMI 50试验MI队列的新数据表明，与非T2DM患者相比，T2DM患者亚组使用沃拉帕沙的获益增加。本研究的目的是严格审查目前关于T2DM患者使用沃拉帕沙的知识，并讨论沃拉帕沙在T2DM中产生有益作用的可能机制。
