Comparative study of tacrolimus and paclitaxel stent coating in the porcine coronary model.
BACKGROUND
Tacrolimus is a potent antiproliferative and immunosuppressive agent allowing for improved endothelial regeneration. The aim of our study was the preclinical evaluation of tacrolimus in a drug eluting nonerodable polymer stent system and its comparison with paclitaxel.


RESULTS
A total of 40 domestic pigs and 10 mini-pigs underwent coronary stenting with a follow-up time between 6 hours and 3 months. Stents were implanted in coronary arteries with an overstretch ratio of 1.2. After 3 days, a 1.73 microg/mm(2) coating produced tacrolimus tissue levels of 20 mumol/l in the coronary artery wall. Effective tissue concentrations were sustained for 28 days. Based on histomorphometric analysis, tacrolimus stent treated vessels had a reduced extent of neointima formation compared with controls at 28 days (-51% compared to control) but not at 3 months. High dose paclitaxel stent coating (1.44 microg/mm(2)) was complicated by unexpected deaths of pigs and thrombotic stent occlusion at control angiography. Long-term porcine data showed no persistent inhibition of neointimal growth by paclitaxel and tacrolimus stent coating.


CONCLUSIONS
Similar to paclitaxel, tacrolimus stent coating reduces neointimal proliferation in the porcine coronary model. However, dosing and long-term efficacy remains a critical issue in stent-based local drug delivery.
Scheller
B
B
Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, 66421 Homburg/Saar, Germany. bruno.scheller@uniklinik-saarland.de
Grandt
A
A
Wnendt
S
S
Lorenz
G
G
Böhm
M
M
Nickenig
G
G
D000818:Animals; D001807:Blood Vessel Prosthesis / Q000009:adverse effects*; D020099:Coated Materials, Biocompatible / Q000737:chemistry; D023903:Coronary Restenosis / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control*; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology / Q000601:surgery; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D004195:Disease Models, Animal; D006083:Graft Occlusion, Vascular / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control*; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D017239:Paclitaxel / Q000008:administration & dosage*; D013552:Swine; D013556:Swine, Miniature; D016559:Tacrolimus / Q000008:administration & dosage*; D016896:Treatment Outcome
D020099:Coated Materials, Biocompatible; D003692:Delayed-Action Preparations; D007166:Immunosuppressive Agents; D017239:Paclitaxel; D016559:Tacrolimus