Author + information
- Received February 15, 2017
- Revision received April 5, 2017
- Accepted May 4, 2017
- Published online August 21, 2017.
- Han Saem Jeong, MD,
- Soon Jun Hong, MD, PhD∗ (, )
- Sang-A Cho, MS,
- Jong-Ho Kim, PhD,
- Jae Young Cho, MD,
- Seung Hun Lee, MD,
- Hyung Joon Joo, MD, PhD,
- Jae Hyoung Park, MD, PhD,
- Cheol Woong Yu, MD, PhD and
- Do-Sun Lim, MD, PhD
- Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Seoul, Republic of Korea
- ↵∗Address for correspondence:
Dr. Soon Jun Hong, Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, 126-1, 5-ka, Anam-dong, Sungbuk-ku, Seoul 136-705, Republic of Korea.
Objectives This study compared adenosine-associated pleiotropic effects of the 2 P2Y12 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 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).
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. (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)
This research was supported by an unconditional grant from AstraZeneca, a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funding from the Ministry of Health & Welfare (grant no. HI14C0209), and a grant from the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning, Republic of Korea (no. NRF-2014R1A2A1A11051998). The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received February 15, 2017.
- Revision received April 5, 2017.
- Accepted May 4, 2017.
- 2017 American College of Cardiology Foundation