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Several investigations have been planned to evaluate the off-target effects of ticagrelor, but are not yet published. 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.
Eighteen pigs were prepared for this study. Three pigs (2 pigs with clopidogrel loading, 1 pig with ticagrelor loading) were excluded owing to significant vasoconstriction before percutaneous coronary intervention. A total of 15 pigs were randomly allocated based on the type of P2Y12 inhibitor. 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.
Percentages of mean neointimal area and area stenosis were significantly lower in the ticagrelor group than in the clopidogrel and prasugrel groups. There were strong positive correlations between OCT and histopathological parameters. Peri-strut inflammation scores were also significantly lower in the ticagrelor group. 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. There were no significant differences in all findings between clopidogrel and prasugrel groups.
Compared to clopidogrel and prasugrel, ticagrelor reduced neointimal formation, endothelial dysfunction, and peri-strut inflammation, which were indicators of neoatherosclerosis and late stent failure after drug-eluting stent implantation.