1. Feasibility, Safety, and Efficacy of a Novel Polymeric Pimecrolimus-Eluting Stent: Traditional Pre-Clinical Safety End Points Failed to Predict 6-Month Clinical Angiographic Results.
- Author
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Ormiston, John A., Webster, Mark W.I., Schwartz, Robert S., Gladding, Patrick, Stewart, James T., Kay, I. Patrick, Ruygrok, Peter N., and Hatrick, Robert
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TACROLIMUS ,MEDICATION safety ,DRUG efficacy ,FEASIBILITY studies ,ANGIOGRAPHY ,CLINICAL trials ,LABORATORY swine ,ANGIOPLASTY - Abstract
Objectives: The aim of this study was to determine the safety and efficacy of a novel pimecrolimus-eluting stent in a porcine coronary model and in a phase I clinical trial. Background: Rapamycin- and paclitaxel-eluting stents reduce the need for repeat intervention by limiting neointimal hyperplasia but might cause delayed healing, pre-disposing patients to late stent thrombosis. Because inflammation plays a key role in restenosis, pimecrolimus, an anti-inflammatory drug, might reduce restenosis without adversely affecting re-endothelialization. Methods: We evaluated a novel polymeric pimecrolimus-eluting stent covered with a thin parylene C diffusion barrier in a porcine coronary model and in a phase I human clinical trial. The clinical study was a prospective, nonrandomized, first-in-human hypothesis-generating study that enrolled 15 patients who had a single de novo native coronary stenosis. Results: At 28 days and 3 months in the porcine model, histopathologic indicators predicted safety and biocompatibility when stents coated with polymer only, drug only, and 2 drug-polymer formulations were compared with bare-metal stents (BMS). In the phase I clinical trial, 15 patients had successful implantation of pimecrolimus-eluting stents. By 6 months, no patient suffered death, myocardial infarction, or stent thrombosis. However, the angiographic restenosis (61%), mean late loss (1.44 mm), and repeat target lesion revascularization (53%) were significantly higher than historical BMS controls. Whereas the primary end point was percent volume obstruction, restenosis was so severe that operators performed intravascular ultrasound examination in only 6 patients. Conclusions: Pimecrolimus-eluting stents induced an exaggerated neointimal hyperplasia at 6 months in comparison with historical controls. [Copyright &y& Elsevier] more...
- Published
- 2009
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