Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Seoul, Republic of Korea.
Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Seoul, Republic of Korea.
JACC Cardiovasc Interv. 2017 Aug 28;10(16):1646-1658. doi: 10.1016/j.jcin.2017.05.064.
This study compared adenosine-associated pleiotropic effects of the 2 P2Y receptor antagonists on vascular function, systemic inflammation, and circulating endothelial progenitor cells (EPCs).
Both ticagrelor and prasugrel have potent antiplatelet effects. However, only ticagrelor inhibits cellular uptake of adenosine.
Using a randomized, crossover design with 10-week follow-up ticagrelor or prasugrel was administered to type 2 diabetic patients with non-ST-segment elevation acute coronary syndrome requiring stent implantation. A total of 62 patients underwent randomization in a 1:1 ratio to receive ticagrelor or prasugrel for 5 weeks followed by a direct cross over to the alternative treatment for 5 additional weeks. Brachial artery flow-mediated dilation, inflammatory markers, and number of circulating EPCs were compared.
Improvement in brachial artery flow-mediated dilation was greater in the ticagrelor group (0.15 ± 0.19 mm vs. -0.03 ± 0.18 mm; p < 0.001). Moreover, ticagrelor compared with prasugrel decreased interleukin 6 (-0.58 ± 0.43 pg/ml vs. -0.05 ± 0.24 pg/ml; p < 0.001), tumor necrosis factor alpha (-5.62 ± 4.40 pg/ml vs. -0.42 ± 2.64 pg/ml; p < 0.001), and increased adiponectin (2.31 ± 2.00 μg/ml vs. 0.08 ± 1.50 μg/ml; p < 0.001) during 10-week follow-up. Other inflammatory cytokines like high-sensitivity C-reactive protein and soluble vascular cell adhesion molecule-1 were decreased in both groups. Ticagrelor compared with prasugrel significantly increased absolute numbers of circulating EPCs CD34+/KDR+ (42.5 ± 37.8 per μl vs. -28.2 ± 23.7 per μl; p < 0.001), CD34+/CD117+ (51.9 ± 77.2 per μl vs. -66.3 ± 45.2 per μl; p < 0.001), and CD34+/CD133+ (55.2 ± 69.2 per μl vs. -28.0 ± 34.1 per μl; p < 0.001).
Compared with prasugrel, ticagrelor significantly decreased inflammatory cytokines such as interleukin 6 and tumor necrosis factor alpha and increased circulating EPCs, contributing to improved arterial endothelial function in diabetic non-ST-segment elevation acute coronary syndrome patients. Thus, data support that pleiotropic effects of ticagrelor beyond its potent antiplatelet effects could contribute to additional clinical benefits. (Comparison of Ticagrelor vs. Prasugrel on Inflammation, Arterial Stiffness, Endothelial Function, and Circulating Endothelial Progenitor Cells in Diabetic Patients With Non-ST Elevation Acute Coronary Syndrome [NSTE-ACS] Requiring Coronary Stenting; NCT02487732).
本研究比较了 2 种 P2Y 受体拮抗剂与腺苷相关的多种效应，以评估其对血管功能、全身炎症和循环内皮祖细胞（EPC）的影响。
替格瑞洛和普拉格雷均具有强大的抗血小板作用。然而，只有替格瑞洛能抑制细胞摄取腺苷。
采用随机、交叉设计，随访 10 周，将需要支架植入的 2 型糖尿病非 ST 段抬高型急性冠脉综合征患者分为替格瑞洛或普拉格雷组。62 例患者按 1:1 比例随机分组，分别接受替格瑞洛或普拉格雷治疗 5 周，然后直接交叉治疗 5 周。比较肱动脉血流介导的扩张、炎症标志物和循环 EPC 数量。
替格瑞洛组肱动脉血流介导的扩张改善更明显（0.15±0.19mm 比-0.03±0.18mm；p<0.001）。此外，与普拉格雷相比，替格瑞洛降低了白细胞介素 6（-0.58±0.43pg/ml 比-0.05±0.24pg/ml；p<0.001）、肿瘤坏死因子-α（-5.62±4.40pg/ml 比-0.42±2.64pg/ml；p<0.001），并增加了脂联素（2.31±2.00μg/ml 比 0.08±1.50μg/ml；p<0.001）。两组的其他炎症细胞因子如高敏 C 反应蛋白和可溶性血管细胞黏附分子 1 也均有所下降。与普拉格雷相比，替格瑞洛显著增加了循环 EPCs CD34+/KDR+（42.5±37.8/μl 比-28.2±23.7/μl；p<0.001）、CD34+/CD117+（51.9±77.2/μl 比-66.3±45.2/μl；p<0.001）和 CD34+/CD133+（55.2±69.2/μl 比-28.0±34.1/μl；p<0.001）的绝对数量。
与普拉格雷相比，替格瑞洛显著降低了白细胞介素 6 和肿瘤坏死因子-α等炎症细胞因子，增加了循环 EPCs，从而改善了糖尿病非 ST 段抬高型急性冠脉综合征患者的动脉内皮功能。因此，数据支持替格瑞洛除了强大的抗血小板作用外，其多效性作用可能会带来额外的临床获益。（替格瑞洛与普拉格雷对需要冠状动脉支架置入的非 ST 段抬高型急性冠脉综合征糖尿病患者炎症、动脉僵硬度、内皮功能和循环内皮祖细胞的影响比较[NSTE-ACS]；NCT02487732）。
