Pimecrolimus and dual pimecrolimus-paclitaxel eluting stents decrease neointimal proliferation in a porcine model.
OBJECTIVE
The purpose of this study was to determine the effectiveness and vascular response of a pimecrolimus drug eluting stent and a combination (pimecrolimus + paclitaxel) stent as compared with bare metal controls in the porcine coronary model.


RESULTS
In the first phase of the study, cobalt chromium stents were loaded with an erodible polymer and either a slow release or a fast release formulation of pimecrolimus. Thirty stents (metal, n = 10; pimecrolimus slow, n = 10; pimecrolimus fast, n = 10) were implanted in the coronary arteries of 10 pigs. At 30 days, neointimal proliferation and inflammation were both significantly less in the pimecrolimus fast release group as compared with the bare metal controls. Endothelialization was complete and equal in all three groups of stents. In the second phase of the study, stents were loaded with an erodible polymer with alternating reservoirs of paclitaxel and pimecrolimus. Twenty stents (8 control stents and 12 dual stents) were implanted in the coronary arteries of seven pigs. At 30 days, neointimal proliferation was significantly less in the dual drug group as compared with the bare metal controls. Endothelialization was complete in both groups of stents, suggesting complete healing of the arteries.


CONCLUSIONS
In a 30-day porcine stent model, pimecrolimus inhibits neointimal proliferation as compared with bare metal stents. Also, the proof of concept of a dual drug eluting stent was established showing both safety and efficacy.
Berg
Ryan
R
Division of Cardiology, Cedars Sinai Medical Center, Los Angeles, California, USA. ryan.berg@cshs.org
Aragon
Joseph
J
Royter
Vladimir
V
Shanley
John F
JF
Cogert
Greg
G
Vermani
Renu
R
Kar
Saibal
S
Eigler
Neal
N
Litvack
Frank
F
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D019917:Blood Vessel Prosthesis Implantation / Q000295:instrumentation*; D065095:Calcineurin Inhibitors; D049109:Cell Proliferation / Q000187:drug effects; D020099:Coated Materials, Biocompatible; D017023:Coronary Angiography; D023903:Coronary Restenosis / Q000000981:diagnostic imaging / Q000473:pathology / Q000517:prevention & control*; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology*; D004195:Disease Models, Animal; D004338:Drug Combinations; D005500:Follow-Up Studies; D006083:Graft Occlusion, Vascular / Q000517:prevention & control; D007166:Immunosuppressive Agents / Q000494:pharmacology; D017239:Paclitaxel / Q000494:pharmacology*; D015607:Stents; D013552:Swine; D016559:Tacrolimus / Q000031:analogs & derivatives* / Q000494:pharmacology; D016896:Treatment Outcome; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology
D000972:Antineoplastic Agents, Phytogenic; D065095:Calcineurin Inhibitors; D020099:Coated Materials, Biocompatible; D004338:Drug Combinations; D007166:Immunosuppressive Agents; C117268:pimecrolimus; D017239:Paclitaxel; D016559:Tacrolimus