Continuous subcutaneous angiopeptin treatment significantly reduces neointimal hyperplasia in a porcine coronary in-stent restenosis model
Hong, M.K.; Kent, K.M.; Mehran, R.; Mintz, G.S.; Tio, F.O.; Foegh, M.; Wong, S.C.; Cathapermal, S.S.; Leon, M.B.
Circulation 95(2): 449-454
1997
ISSN/ISBN: 0009-7322 PMID: 9008463 Document Number: 475601
Background: In-stent restenosis results primarily from neointimal hyperplasia. This study evaluated the efficacy and the optimal mode of administration of angiopeptin, a somatostatin analogue with antiproliferative activity, in a porcine coronary in-stent restenosis model. Methods and Results: Forty pigs were randomly assigned to one of four groups (n = 10 per group): (1) controls receiving saline infusion at the site of stent implantation via a local delivery catheter, (2) local treatment group receiving one-time treatment (200 mu-g angiopeptin) at the site of stent placement. (3) systemic treatment group receiving continuous angiopeptin over a 1-week period via a subcutaneous osmotic pump (200 mu-g/kg total dose), and (4) combined local and systemic treatment group. Then, one oversized Palmaz-Schatz stent (mean ratio of stent to artery diameters, 1.3:1) was implanted in the left anterior descending coronary artery. The degree of neointimal reaction was evaluated 4 weeks later by angiography (maximal percent diameter stenosis), intravascular ultrasound (total in-stent neointimal volume), and histology (maximal area stenosis). Systemic treatment produced the least neointimal hyperplasia and significantly reduced in-stent restenosis compared with the control group by all end points, despite similar degrees of injury. Angiography showed 25+-17% versus 50+-17% diameter stenosis in the systemic angiopeptin group versus the control group (P lt .0001), intravascular ultrasound revealed 23+-10 versus 58+-27 mm-3 neointimal volume in the systemic angiopeptin versus control group (P=.0002), and histology showed 41+-16% versus 69+-18% area stenosis (P=.0016) in the systemic angiopeptin versus control group. Plasma angiopeptin levels revealed rapid clearance (within 6 hours) after local therapy, whereas the levels persisted for up to 2 weeks in the systemic group. Conclusions: This study shows that continuous subcutaneous treatment with angiopeptin after stent implantation significantly reduces in-stent restenosis by inhibiting neointimal hyperplasia.