Campo Gianluca, Vieceli Dalla Sega Francesco, Pavasini Rita, Aquila Giorgio, Gallo Francesco, Fortini Francesca, Tonet Elisabetta, Cimaglia Paolo, Del Franco Annamaria, Pestelli Gabriele, Pecoraro Alessandro, Contoli Marco, Balla Cristina, Biscaglia Simone, Rizzo Paola, Ferrari Roberto
Gianluca Campo, MD, Cardiovascular Institute, Azienda Ospedaliero-Universitaria S.Anna, Via A. Moro 8, Cona (FE), Italy, Tel.: +39 0532237079, Fax: +39 0532241885, E-mail:
Thromb Haemost. 2017 Mar 23;117(6):1208-1216. doi: 10.1160/TH16-12-0973.
Patients with SCAD and concomitant COPD are at high risk of cardiovascular adverse events, due to chronic inflammation, responsible of endothelial dysfunction, oxidative stress and heightened platelet reactivity (PR). The objective of this randomised clinical trial was to test if ticagrelor is superior to clopidogrel in improving endothelial function in patients with stable coronary artery disease (SCAD) and concomitant chronic obstructive pulmonary disease (COPD). Forty-six patients with SCAD and COPD undergoing percutaneous coronary intervention (PCI) were randomly assigned to receive clopidogrel (n=23) or ticagrelor (n=23) on top of standard therapy with aspirin. The following parameters were assessed at baseline and after 1 month: i) rate of apoptosis and ii) nitric oxide (NO) levels in human umbilical vein endothelial cells (HUVECs), iii) levels of reactive oxygen species (ROS) in peripheral blood mononuclear cell, iv) 29 cytokines/chemokines, v) on-treatment PR. The primary endpoint of the study was the 1-month rate of HUVECs apoptosis. The rate of apoptosis after 1 month was significantly lower in patients treated with ticagrelor (7.4 ± 1.3 % vs 9.3 ± 1.5 %, p<0.001), satisfying the pre-specified primary endpoint. In the ticagrelor arm, levels of NO were higher (10.1 ± 2.2 AU vs 8.5 ± 2.6 AU, p=0.03) while those of ROS (4 ± 1.8 AU vs 5.7 ± 2.8 AU, p=0.02) and P2Y reactivity units (52 ± 70 PRU vs 155 ± 62 PRU, p<0.001) were lower. There were no differences in cytokines/chemokines levels and aspirin reactivity units between groups. In patients with SCAD and COPD undergoing PCI, ticagrelor, as compared to clopidogrel is superior in improving surrogate markers of endothelial function and on-treatment PR (ClinicalTrials.gov, NCT02519608).
伴有慢性阻塞性肺疾病（COPD）的自发性冠状动脉夹层（SCAD）患者因慢性炎症而面临心血管不良事件的高风险，慢性炎症会导致内皮功能障碍、氧化应激和血小板反应性（PR）增强。这项随机临床试验的目的是检验替格瑞洛在改善稳定型冠状动脉疾病（SCAD）合并慢性阻塞性肺疾病（COPD）患者的内皮功能方面是否优于氯吡格雷。46例接受经皮冠状动脉介入治疗（PCI）的SCAD和COPD患者被随机分配，在阿司匹林标准治疗基础上接受氯吡格雷（n = 23）或替格瑞洛（n = 23）治疗。在基线和1个月后评估以下参数：i）人脐静脉内皮细胞（HUVECs）的凋亡率和ii）一氧化氮（NO）水平，iii）外周血单核细胞中的活性氧（ROS）水平，iv）29种细胞因子/趋化因子，v）治疗期间的PR。该研究的主要终点是HUVECs 1个月的凋亡率。替格瑞洛治疗的患者1个月后的凋亡率显著更低（7.4±1.3%对9.3±l.5%，p<0.001），达到预先指定的主要终点。在替格瑞洛组，NO水平更高（10.1±2.2 AU对8.5±2.6 AU，p = 0.03），而ROS水平（4±1.8 AU对5.7±2.8 AU，p = 0.02）和P2Y反应单位（52±70 PRU对155±62 PRU，p<0.001）更低。两组之间细胞因子/趋化因子水平和阿司匹林反应单位没有差异。在接受PCI的SCAD和COPD患者中，与氯吡格雷相比，替格瑞洛在改善内皮功能替代指标和治疗期间的PR方面更具优势（ClinicalTrials.gov，NCT02519608）。
