Comparison of Ticagrelor Versus Prasugrel for Inflammation, Vascular Function, and Circulating Endothelial Progenitor Cells in Diabetic Patients With Non-ST-Segment Elevation Acute Coronary Syndrome Requiring Coronary Stenting A Prospective, Randomized, Crossover Trial

Abstract

OBJECTIVES This study compared adenosine-associated pleiotropic effects of the 2 P2Y(12) receptor antagonists on vascular function, systemic inflammation, and circulating endothelial progenitor cells (EPCs). BACKGROUND Both ticagrelor and prasugrel have potent antiplatelet effects. However, only ticagrelor inhibits cellular uptake of adenosine. METHODS 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. RESULTS 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 mu g/ml vs. 0.08 +/- 1.50 mu g/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 mu l vs. -28.2 +/- 23.7 per mu l; p < 0.001), CD34+/CD117+ (51.9 +/- 77.2 per mu l vs. -66.3 +/- 45.2 per mu l; p < 0.001), and CD34+/CD133+ (55.2 +/- 69.2 per mu l vs. -28.0 +/- 34.1 per mu l; p < 0.001). CONCLUSIONS 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. (C) 2017 by the American College of Cardiology Foundation.