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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

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^_*,,, Robert Hatrick, MBBS

^_* Mercy Angiography, Auckland, New Zealand
Auckland Heart Group, Auckland, New Zealand
Auckland City Hospital, Auckland, New Zealand
Minneapolis Heart Institute and Foundation, Minneapolis, Minnesota

^_* Reprint requests and correspondence: Dr. John A. Ormiston, Mercy Angiography, PO Box 9911, Newmarket, Epsom, Auckland, New Zealand (Email: johno{at}mercyangiography.co.nz).

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.

Key Words: anti-inflammatory • drug-eluting stent • pimecrolimus • pre-clinical • restenosis

Abbreviations and Acronyms   BMS = bare-metal stent(s)   DES = drug-eluting stent(s)   IVUS = intravascular ultrasound   mTOR = mammalian target of rapamycin   PCI = percutaneous coronary intervention   QCA = quantitative coronary angiography   TLR = target lesion revascularization   TVR = target vessel revascularization

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				M. Vorpahl, A. V. Finn, M. Nakano, and R. Virmani Do We Really Understand Pimecrolimus? J. Am. Coll. Cardiol. Intv., October 1, 2009; 2(10): 1025 - 1027. [Full Text] [PDF]