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

Han Saem Jeong, Soon Jun Hong, Sang A. Cho, Jong Ho Kim, Jae Young Cho, Seung Hun Lee, Hyung Joon Joo, Jae Hyoung Park, Cheol Woong Yu, Do-Sun Lim

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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)

Original languageEnglish
Pages (from-to)1646-1658
Number of pages13
JournalJACC: Cardiovascular Interventions
Volume10
Issue number16
DOIs
Publication statusPublished - 2017 Aug 28

Fingerprint

Acute Coronary Syndrome
Cross-Over Studies
Blood Vessels
Inflammation
Brachial Artery
Adenosine
Dilatation
Interleukin-6
Purinergic P2Y Receptor Antagonists
Tumor Necrosis Factor-alpha
Ticagrelor
Endothelial Progenitor Cells
Prasugrel Hydrochloride
Cytokines
Vascular Stiffness
Vascular Cell Adhesion Molecule-1
Adiponectin
Random Allocation
C-Reactive Protein
Stents

Keywords

  • acute coronary syndrome
  • diabetic patients
  • pleiotropic effect
  • prasugrel
  • ticagrelor

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

@article{0cc304c0edd0404d83510513ca4e43fa,
title = "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 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)",
keywords = "acute coronary syndrome, diabetic patients, pleiotropic effect, prasugrel, ticagrelor",
author = "Jeong, {Han Saem} and Hong, {Soon Jun} and Cho, {Sang A.} and Kim, {Jong Ho} and Cho, {Jae Young} and Lee, {Seung Hun} and Joo, {Hyung Joon} and Park, {Jae Hyoung} and Yu, {Cheol Woong} and Do-Sun Lim",
year = "2017",
month = "8",
day = "28",
doi = "10.1016/j.jcin.2017.05.064",
language = "English",
volume = "10",
pages = "1646--1658",
journal = "JACC: Cardiovascular Interventions",
issn = "1936-8798",
publisher = "Elsevier Inc.",
number = "16",

}

TY - JOUR

T1 - 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

T2 - A Prospective, Randomized, Crossover Trial

AU - Jeong, Han Saem

AU - Hong, Soon Jun

AU - Cho, Sang A.

AU - Kim, Jong Ho

AU - Cho, Jae Young

AU - Lee, Seung Hun

AU - Joo, Hyung Joon

AU - Park, Jae Hyoung

AU - Yu, Cheol Woong

AU - Lim, Do-Sun

PY - 2017/8/28

Y1 - 2017/8/28

N2 - 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)

AB - 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)

KW - acute coronary syndrome

KW - diabetic patients

KW - pleiotropic effect

KW - prasugrel

KW - ticagrelor

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