Continuous subcutaneous angiopeptin treatment significantly reduces neointimal hyperplasia in a porcine coronary in-stent restenosis model.
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.


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 (micrograms 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 micrograms/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.
Hong
M K
MK
Department of Internal Medicine (Cardiology Division) of the Washington (DC) Hospital Center, Washington, DC, USA.
Kent
K M
KM
Mehran
R
R
Mintz
G S
GS
Tio
F O
FO
Foegh
M
M
Wong
S C
SC
Cathapermal
S S
SS
Leon
M B
MB
D000818:Animals; D002317:Cardiovascular Agents / Q000097:blood / Q000627:therapeutic use*; D017023:Coronary Angiography; D003327:Coronary Disease / Q000097:blood / Q000473:pathology / Q000628:therapy*; D006965:Hyperplasia; D007279:Injections, Subcutaneous; D009842:Oligopeptides / Q000097:blood / Q000627:therapeutic use*; D010456:Peptides, Cyclic; D012008:Recurrence; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D015607:Stents; D013552:Swine; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology*; D018084:Ultrasonography, Interventional
D002317:Cardiovascular Agents; D009842:Oligopeptides; D010456:Peptides, Cyclic; C060347:lanreotide; D013004:Somatostatin