Carotid Stent Restenosis and Thrombosis in Rabbits: The Effect of Antiplatelet Agents

Abstract

Background: The purpose of the study was the comparative assessment of ticagrelor and clopidogrel effects on carotid post-balloon injury (PBI) and on post carotid artery stenting (CAS) rate of in-stent restenosis (ISR) and in-stent thrombosis in atherosclerotic rabbits. Methods: Forty-eight New Zealand white rabbits on high-fat diet were randomized into 4 groups: A1: PBI and clopidogrel (30 mg/kg/d), A2: PBI and ticagrelor (21 mg/kg twice daily), B1: PBI, CAS, and clopidogrel (30 mg/kg/d), B2: PBI, CAS, and ticagrelor (21 mg/kg twice daily). All rabbits received orally aspirin (10 mg/kg/d) and interventions were performed in their right carotid arteries (RCAs). Optical coherence tomography (OCT) and carotid angiography were performed at end point, while platelet aggregation and lipid profile were measured. After euthanasia both carotids were obtained for histological examination. Results: In B1 group, 3 rabbits presented thrombotic total occlusion of the stents, while none such episode was observed in B2 group. The neointimal areas in RCAs, calculated by OCT, did not differ between A1 and A2 groups, and between B1 and B2 groups ( P > .05). From the histological findings, the intima/(media + intima) percentage (%) in RCAs of balloon-injured rabbits did not present any difference between groups ( P = .812). Similarly, the immunohistochemically determined accumulation of endothelial cells and macrophages on vascular walls was equivalent between groups ( P > .05). Conclusion: Following carotid balloon injury and stenting, clopidogrel and ticagrelor did not show any differential effects on the extent of neointimal formation and ISR in atherosclerotic rabbits receiving aspirin. Three thrombotic stent occlusions were noted in the clopidogrel treatment group, but this finding was not statistically significant.

The Effects of Short/Long-Term Administration of Dual Antiplatelet Therapy on Restenosis in Patients With Carotid Artery Stenting

“…However, they discovered that ticagrelor was more effective on intra-stent thrombosis. 22 Another attempt proved no difference in ISR between the cilostazol group after the CAS procedure and the patients who underwent the standard procedure. 23 It was also stated that statins affected the regulation of carotid neointimal hyperplasia.…”

“…However, no definitive results were reached. 22 Kadoglou et al 22 showed that the use of ticagrelor and clopidogrel had similar effects on ISR prevention. The effects of these agents on neointimal hyperplasia and ISR in rabbits undergoing CAS procedure could not be demonstrated.…”

“…23 It was also stated that statins affected the regulation of carotid neointimal hyperplasia. 22,24 Some authors have argued that valsartan can prevent neointimal hyperplasia after a CAS procedure by suppressing endothelial cell damage. 25 Studies on post-CAS restenosis in plaque morphologies have shown that highly calcified carotid plaques are more susceptible to developing ISR.…”

Optimal periprocedural antithrombotic treatment in carotid interventions: An international, multispecialty, expert review and position statement

“…[52][53][54] An experimental study comparing the effects of clopidogrel vs. ticagrelor on post-balloon injury, in-stent restenosis and in-stent thrombosis in an atherosclerotic rabbit model undergoing carotid balloon injury ± CAS did not demonstrate any differences between the two antiplatelet agents. 55 Nevertheless, a drawback of ticagrelor as part of DAPT is its higher bleeding risk compared with clopidogrel. 53,54 Antiplatelet/antithrombotic treatment for patients with crescendo TIA/ stroke in evolution A crescendo TIA is defined as repetitive TIA episodes over hours or days followed by return to normal neurologic status.…”