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. METHODS AND 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.
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. METHODS AND 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.
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