Antiplatelet Versus Warfarin Therapy: Platelet, Neutrophil, and Thrombus Deposition for Intracoronary Stents in a Porcine Model

Abstract

Antiplatelet therapy may offer an advantage over warfarin in reducing adverse clinical events after intracoronary stem implantation. The mechanism of this effect has not been elucidated but platelet adhesion may play a predominant role in the process of subacute stent thrombosis. This study compared the effect on platelet, neutrophil, and thrombus deposition of three different anticoagulation regimens (aspirin/warfarin vs aspirin/ticlopidine vs aspirin alone) after intracoronary stenting in juvenile swine. Thirty stents were deployed in 15 juvenile farm swine randomized to one of 3 anticoagulation protocols: aspirin 325 mg/day; aspirin 325 mg/day and ticlopidine 500 mg/day; aspirin 325 mg/day and warfarin 0.1 mg/kg/day. Autologous platelets were labeled using 111Indium‐oxime and a slotted tube metal stent was deployed using a high pressure balloon. Platelet deposition in the stented segment was determined at 24 hours. Each segment was analyzed by light microscopy to document an injury score; mean and maximum thrombus deposition per strut were measured; and neutrophils were counted on each metal strut and in the vessel wall. Platelet deposition at 24 hours was significantly higher in the aspirin/warfarin group (3.69 ± 1.16 ± 108 plts/cm2) than in the aspirin/ticlopidine (1.74 ± 0.45 ± 108 plts/cm2, P = 0.0009) or aspirin (2.42 ± 2.13 ± 108 plts/cm2, P = 0.03) groups. There was no significant difference between the aspirin and aspirin/ticlopidine groups (P = 0.9). Mean thrombus area per strut was significantly greater in the aspirin/warfarin group (0.027 ± 0.006 mm2) compared to the aspirin/ticlopidine group (0.017 ± 0.002 mm2, P = 0.002). The majority of the thrombus (79%) but minority of neutrophils (24%) were found on the stent struts. In this coronary stent model, warfarin given with aspirin was associated with greater thrombogenicity and more platelet deposition than either aspirin/ticlopidine or aspirin alone.