Stent‐based delivery of ABT‐578 via a phosphorylcholine surface coating reduces neointimal formation in the porcine coronary model

Abstract

Stent-based delivery of the antiproliferative and immunosuppressive macrocyclic lactone sirolimus reduces neointimal formation and restenosis by cytostatic inhibition of vascular smooth muscle cell proliferation. The objective of this study was to determine the feasibility and efficacy of stent-based delivery of ABT-578, a structurally unique macrocyclic lactone. Stainless steel balloon-expandable stents were coated with thin layer of phosphorylcholine (PC) or PC with ABT-578 (10 microg/mm). Fifteen juvenile domestic pigs underwent placement of oversized bare metal (n = 15), PC (n = 8), and PC with ABT-578 (n = 9) stents in the coronary arteries. At 28 days, histology demonstrated similar mean injury scores for the control, PC-, and ABT-578-coated stents. The mean neointimal area (mm2) was significantly reduced for ABT-578 (1.70 +/- 0.47) as compared with PC (2.82 +/- 1.24) and control (2.89 +/- 1.91) stents (P < or = 0.05). The 40% reduction in neointimal area resulted in significantly less mean percent diameter stenosis for ABT-578 (19.4% +/- 4.0%) as compared with PC (30.3 +/- 12.1 %) and control (29.4% +/- 15.5%) stents (P < or = 0.03). Twelve of the 45 bare metal stent cross-sections (26.7%) exhibited a giant cell reaction, while none of the sections from the ABT-578-eluting stents had a giant cell reaction (P = 0.004). Stent-based delivery of ABT-578 via a PC surface coating inhibits neointimal formation at 28 days in the porcine coronary model. Further study is necessary to determine the dose-response and long-term effects ABT-578-eluting stents in the porcine coronary model.