Intramural Delivery of Recombinant Apolipoprotein A-I Milano /Phospholipid Complex (ETC-216) Inhibits In-Stent Stenosis in Porcine Coronary Arteries

Abstract

Background— We have previously demonstrated vasculoprotective effects after repeated intravenous administration of recombinant apolipoprotein A-I _Milano (apoA-I _m )/phospholipid complex. In this study, we sought to determine the effects of local recombinant apoA-I _m /1-palmitoyl,2-oleoyl phosphatidylcholine complex (ETC-216) delivered intramurally via the Infiltrator catheter on luminal narrowing in a porcine coronary artery stent overstretch injury model. Methods and Results— In twelve domestic swine (≈25 kg), two arteries each were infiltrated with 0.4 mL ETC-216 (14 mg/mL) or vehicle control immediately before deployment of GFX stents (stent:artery ratio=1.3:1). Animals were euthanized at day 28, and evaluation by QCA revealed a significant improvement in mean lumen loss index with ETC-216 treatment (21±22% versus 43±13% lumen loss; P =0.01). Histomorphometric analysis showed that ETC-216 treatment significantly reduced the intimal area (6.7±1.5 versus 5.2±1.4 mm ² , −22%; P =0.02) and the stenosis index (0.76±0.15 versus 0.59±0.15; P =0.01), and increased the lumen area (2.1±1.4 versus 3.7±1.8 mm ² , +76%; P =0.02). Regression analysis showed significant differences in lumen area ( P =0.004), neointimal area ( P =0.003), stenosis index ( P =0.001), and neointimal thickness ( P =0.003) adjusted for injury score in favor of ETC-216. Conclusions— A single intramural administration of ETC-216 significantly inhibited injury-induced luminal narrowing in the porcine stent overstretch model through reduction of intimal hyperplasia. These data show that local intracoronary delivery of ETC-216 may be useful to prevent restenosis after coronary stenting.