Author + information
- Received June 13, 2009
- Revision received July 13, 2009
- Accepted August 20, 2009
- Published online October 1, 2009.
- John A. Ormiston, MBChB⁎,†,‡,⁎ (, )
- Mark W.I. Webster, MBChB⁎,†,‡,
- Robert S. Schwartz, MD§,
- Patrick Gladding, MBChB‡,
- James T. Stewart, MD⁎,†,‡,
- I. Patrick Kay, MBChB⁎,
- Peter N. Ruygrok, MD⁎,†,‡ and
- Robert Hatrick, MBBS‡
- ↵⁎Reprint requests and correspondence:
Dr. John A. Ormiston, Mercy Angiography, PO Box 9911, Newmarket, Epsom, Auckland, New Zealand
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.
- Received June 13, 2009.
- Revision received July 13, 2009.
- Accepted August 20, 2009.
- American College of Cardiology Foundation