Effects of ticagrelor on neointimal hyperplasia and endothelial function, compared with clopidogrel and prasugrel, in a porcine coronary stent restenosis model.

Abstract

BACKGROUND:

Several investigations have been conducted to evaluate the off-target effects of ticagrelor. The aim of the present study was to evaluate the off-target effects of ticagrelor such as neointimal formation and endothelial function after drug-eluting stent implantation in a porcine restenosis model.

METHODS:

A total of 30 pigs were randomly allocated based on the following P2Y12 inhibitor: (1) clopidogrel 300mg loading plus 75mg maintenance (n=10); (2) prasugrel 60mg loading plus 10mg maintenance (n=10); (3) ticagrelor 180mg loading plus 180mg maintenance (n=10). In each group, zotarolimus-eluting stents were implanted in the proximal portion of the left anterior descending artery and left circumflex artery. One month after stenting, the animals underwent follow-up angiography, endothelial function assessment, optical coherence tomography (OCT) and histopathological analysis.

RESULTS:

Regarding vasomotor responses to acetylcholine infusion, there were significant vasoconstrictions to maximal acetylcholine infusion in the clopidogrel and prasugrel group compared with those in the ticagrelor group. The mean neointimal area were significantly lower in the ticagrelor group (1.0±0.3 by OCT, 0.9±0.3 by histology), than in the clopidogrel (1.8±0.7, p=0.003, 1.6±0.8, p=0.030) and prasugrel (1.8±0.5, p=0.001, 1.5±0.5, p=0.019) groups. Percentages of moderate to dense peri-strut inflammatory cell infiltration were significantly lower in the ticagrelor group (9.0%) compared with the clopidogrel (17.3%, p<0.001) and prasugrel groups (15.7%, p=0.002). There were no significant differences in all findings between clopidogrel and prasugrel groups.

CONCLUSIONS:

Compared to clopidogrel and prasugrel, ticagrelor reduced neointimal formation, endothelial dysfunction, and peri-strut inflammation.

• Authors: Hyun Kuk Kim, Myung Ho Jeong, Kyung Seob Lim, Jung Ha Kim, Han Chul Lim, Min Chul Kim, Young Joon Hong, Sung Soo Kim, Keun-Ho Park, Kyoung-Sig Chang
• Journal: International journal of cardiology (Int J Cardiol) Vol. 240 Pg. 326-331 (Aug 01 2017) ISSN: 1874-1754 [Electronic] Netherlands
• PMID: 28487152 (Publication Type: Comparative Study, Journal Article)
• Copyright: Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical References

• Purinergic P2Y Receptor Antagonists
• Clopidogrel
• Prasugrel Hydrochloride
• Ticagrelor
• Adenosine
• Ticlopidine

Topics

• Adenosine (administration & dosage, adverse effects, analogs & derivatives)
• Animals
• Clopidogrel
• Coronary Restenosis (chemically induced, diagnostic imaging, drug therapy)
• Drug-Eluting Stents (adverse effects)
• Endothelium, Vascular (diagnostic imaging, drug effects, physiology)
• Hyperplasia (diagnostic imaging, drug therapy)
• Male
• Neointima (diagnostic imaging, drug therapy)
• Prasugrel Hydrochloride (administration & dosage, adverse effects)
• Purinergic P2Y Receptor Antagonists (administration & dosage, adverse effects)
• Random Allocation
• Swine
• Ticagrelor
• Ticlopidine (administration & dosage, adverse effects, analogs & derivatives)
• Tomography, Optical Coherence (methods)
• Treatment Outcome