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Angiopeptin has been shown to reduce in-stent restenosis in various animal models. Meanwhile, BiodivYsio DD phosphorylcholine (PC)-coated stent provides a platform for local delivery of antiproliferative agents to the coronary artery. We studied the feasibility, safety, and impact on tissue growth of angiopeptin-eluting BiodivYsio DD PC-coated stents in human native de novo coronary lesions. We enrolled 14 patients (16 lesions) who underwent intravascular ultrasound (IVUS)-guided angiopeptin-eluting stent implantation in native coronary arteries between 3.0 and 4.0 mm in diameter with lesion length ≤ 18 mm. We successfully implanted 13 stents loaded with 22 μg of angiopeptin and three stents with 126 μg of angiopeptin. No major adverse cardiac events or target vessel failure occurred at 1-year clinical follow-up. All patients underwent 6-month angiographic and volumetric IVUS follow-up. In-stent late loss was 0.46 ± 0.32 mm in the low-dose group and 0.26 ± 0.14 mm in the high-dose group. Binary restenosis rate was 0%. Follow-up percentage neointimal hyperplasia by IVUS was 18.4% ± 22.5% for the low-dose group and 10.2% ± 5.8% for the high-dose group, respectively. There were no edge effect and late stent malapposition. Angiopeptin-eluting BiodivYsio DD PC stent appears feasible and safe in treating native de novo coronary lesions with modest degree of neointimal hyperplasia. © 2005 Wiley-Liss, Inc.