Efficacy and safety of pimecrolimus-eluting stents in porcine coronary arteries

Waksman, Ron; Pakala, Rajbabu; Baffour, Richard; Hellinga, David; Seabron, Rufus; Tio, Fermin O.; Wittchow, Eric; Tittelbach, Michael; Diener, Tobias; Harder, Claus; Virmani, Renu; Jones, Russel

doi:10.1016/j.carrev.2007.09.003

« Previous Next »Cardiovascular Revascularization Medicine
Volume 8, Issue 4 , Pages 259-274, October 2007

Efficacy and safety of pimecrolimus-eluting stents in porcine coronary arteries

Ron Waksman
- Cardiovascular Research Institute, Washington Hospital Center, Washington DC, USA
- Corresponding author. Washington Hospital Center, 110 Irving Street, NW, Suite 4B-1, Washington DC, 20010, USA. Tel.: +1 202 877 2812; fax: +1 202 877 2715.
Rajbabu Pakala
- Cardiovascular Research Institute, Washington Hospital Center, Washington DC, USA
Richard Baffour
- Cardiovascular Research Institute, Washington Hospital Center, Washington DC, USA
David Hellinga
- Cardiovascular Research Institute, Washington Hospital Center, Washington DC, USA
Rufus Seabron
- Cardiovascular Research Institute, Washington Hospital Center, Washington DC, USA
Fermin O. Tio
- Biomedical Research Foundation of South Texas, San Antonio, TX, USA
Eric Wittchow
- Vascular Interventions R&D group, BIOTRONIK GmbH & Co. KG., Erlangen, Germany
Michael Tittelbach
- Vascular Interventions R&D group, BIOTRONIK GmbH & Co. KG., Erlangen, Germany
Tobias Diener
- Vascular Interventions R&D group, BIOTRONIK GmbH & Co. KG., Erlangen, Germany
Claus Harder
- Vascular Interventions R&D group, BIOTRONIK GmbH & Co. KG., Erlangen, Germany
Renu Virmani
- CV Path, Gaithersburg, MD, USA
Russel Jones
- CV Path, Gaithersburg, MD, USA

Received 19 September 2007; accepted 19 September 2007.

Abstract

Objective

We aimed to evaluate an effective dosage and safety profile of pimecrolimus as an anti-inflammatory drug for drug-eluting stents.

Methods

In the dose finding study, coronary arteries of 20 domestic swine were randomly implanted with bare metal stents (ProKinetic and Guidant Vision), the ProKinetic stent with polylactic acid (PLLA), and pimecrolimus-eluting stents (32, 75, and 120 μg) over a period of 4 weeks. In addition, pimecrolimus (75 μg) and ProKinetic stents were randomly implanted into six swine over 3 months. In the safety study, the ProKinetic stent, the ProKinetic stent with PLLA, mid- (45 μg) and high-dose pimecrolimus (120 μg), and overlapping mid-dose stents were implanted over a period of 4 weeks. Mid-dose, ProKinetic stent, and ProKinetic stent with PLLA were implanted over a period of 3 months.

Results

The dose finding study revealed excellent luminal patency with low percent occlusion (≈29% vs. ≈41%), injury (0.53–0.59 vs. 1.25), and inflammation (0.78–0.97 vs. 1.08) for the pimecrolimus group compared with the vision group. The safety study arm showed similar angiographic results for all tested groups, with a significantly larger minimal lumen diameter for pimecrolimus stents compared to PLLA stents. Except for the high-dose group and overlapping area of the overlapping group, promising morphometric results were found for pimecrolimus compared to bare metal stents.

Conclusions

Present data suggest that pimecrolimus-eluting stents are safe and have a similar healing profile to bare metal stents. They may suppress inflammation, leading to a reduced intimal response and a milder inflammatory reaction in a porcine model.

Keywords: Pimecrolimus-eluting stent, Porcine, In-stent restenosis