BACKGROUND Despite increased atherothrombotic risk in type 2 diabetes mellitus, (T2DM) the best preventative antithrombotic strategy remains undetermined. We defined the effects of three antiplatelet agents on functional readout and biomarker kinetics in platelet activation and coagulation in patients with T2DM. MATERIALS AND METHODS 56 patients with T2DM were randomised to antiplatelet monotherapy with aspirin 75 mg once daily (OD), clopidogrel 75 mg OD or prasugrel 10 mg OD during three periods of a crossover study. Platelet aggregation (PA) was determined by light-transmittance aggregometry and P-selectin expression by flow cytometry. Markers of fibrin clot dynamics, inflammation and coagulation were measured. Plasma levels of 14 miRNA were assessed by quantitative polymerase chain reactions. RESULTS Of the 56 patients, 24 (43%) were receiving aspirin for primary prevention of ischaemic events and 32 (57%) for secondary prevention. Prasugrel was the strongest inhibitor of ADP-induced PA (mean ± SD maximum response to 20μmol/L ADP 77.6 ± 8.4% [aspirin] vs. 57.7 ± 17.6% [clopidogrel] vs. 34.1 ± 14.1% [prasugrel], p < 0.001), P-selectin expression (30 μmol/L ADP; 45.1 ± 21.4% vs. 27.1 ± 19.0% vs. 14.1 ± 14.9%, p < 0.001) and collagen-induced PA (2 μg/mL; 62.1 ± 19.4% vs. 72.3 ± 18.2% vs. 60.2 ± 18.5%, p < 0.001). Fibrin clot dynamics and levels of coagulation and inflammatory proteins were similar. Lower levels of miR-24 (p = 0.004), miR-191 (p = 0.019), miR-197 (p = 0.009) and miR-223 (p = 0.014) were demonstrated during prasugrel-therapy vs. aspirin. Circulating miR-197 was lower in those cardiovascular disease during therapy with aspirin (p = 0.039) or prasugrel (p = 0.0083). CONCLUSIONS Prasugrel monotherapy in T2DM provided potent platelet inhibition and reduced levels of a number of platelet-associated miRNAs. miR-197 is a potential marker of cardiovascular disease in this population. Clinical outcome studies investigating prasugrel monotherapy are warranted in individuals with T2DM. Trial registration EudraCT, 2009-011907-22. Registered 15 March 2010, https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-011907-22/GB.

中文翻译：

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阿司匹林，氯吡格雷和普拉格雷单药治疗2型糖尿病的患者：一项对血栓形成标志物和microRNA水平影响的双盲随机对照试验。

背景技术尽管2型糖尿病（T2DM）的血栓形成风险增加，但仍未确定最佳的预防性抗血栓形成策略。我们定义了三种抗血小板药物对T2DM患者血小板活化和凝血中功能读数和生物标志动力学的影响。材料与方法将56例T2DM患者随机分为三组，分别接受每日一次一次阿司匹林75毫克（OD），氯吡格雷75毫克OD或普拉格雷10毫克OD的抗血小板单一疗法。通过透光聚集法测定血小板聚集（PA），通过流式细胞术测定P-选择蛋白表达。测量纤维蛋白凝块动力学，炎症和凝血的标志物。通过定量聚合酶链反应评估了14种miRNA的血浆水平。结果56例患者中 有24名（43％）接受阿司匹林用于一级预防缺血事件，有32名（57％）接受二级预防。普拉格雷是ADP诱导的PA的最强抑制剂（平均±SD对20μmol/ L ADP的最大反应77.6±8.4％[阿司匹林] vs. 57.7±17.6％[氯吡格雷] vs. 34.1±14.1％[prasugrel]，p <0.001 ），P-选择素表达（30μmol/ L ADP; 45.1±21.4％vs. 27.1±19.0％vs. 14.1±14.9％，p <0.001）和胶原蛋白诱导的PA（2μg/ mL; 62.1±19.4％vs 72.3±18.2％与60.2±18.5％，p <0.001）。纤维蛋白凝块动力学以及凝血和炎性蛋白水平相似。在普拉格雷治疗期间，与阿司匹林相比，miR-24（p = 0.004），miR-191（p = 0.019），miR-197（p = 0.009）和miR-223（p = 0.014）的水平较低。阿司匹林治疗期间那些心血管疾病中循环miR-​​197的含量较低（p = 0。039）或普拉格雷（p = 0.0083）。结论普拉提格雷单药治疗T2DM可有效抑制血小板，并降低许多与血小板相关的miRNA的水平。miR-197是该人群中心血管疾病的潜在标志。对于患有T2DM的个体，有必要进行研究普拉格雷单药治疗的临床结果研究。审判注册EudraCT，2009-011907-22。于2010年3月15日注册，https：//www.clinicaltrialsregister.eu/ctr-search/trial/2009-011907-22/GB。审判注册EudraCT，2009-011907-22。于2010年3月15日注册，https：//www.clinicaltrialsregister.eu/ctr-search/trial/2009-011907-22/GB。审判注册EudraCT，2009-011907-22。于2010年3月15日注册，https：//www.clinicaltrialsregister.eu/ctr-search/trial/2009-011907-22/GB。