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 μg 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 μg/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<.0001), intravascular ultrasound revealed 23±10 versus 58±27 mm3 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.
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Physiology (medical)