Efficacy and safety of pimecrolimus-eluting stents in porcine coronary arteries.
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 microg) over a period of 4 weeks. In addition, pimecrolimus (75 microg) 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 microg) and high-dose pimecrolimus (120 microg), 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 (approximately 29% vs. approximately 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.
Cardiovascular Research Institute, Washington Hospital Center, Washington, DC 20010, USA. ron.waksman@medstar.net
Ron
R
Waksman
Rajbabu
R
Pakala
Richard
R
Baffour
David
D
Hellinga
Rufus
R
Seabron
Fermin O
FO
Tio
Eric
E
Wittchow
Michael
M
Tittelbach
Tobias
T
Diener
Claus
C
Harder
Renu
R
Virmani
Russel
R
Jones
D000704:Analysis of Variance; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D017023:Coronary Angiography; D003327:Coronary Disease / Q000473:pathology / Q000628:therapy*; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology; D004195:Disease Models, Animal; D054855:Drug-Eluting Stents; D011897:Random Allocation; D018709:Statistics, Nonparametric; D013552:Swine; D016559:Tacrolimus / Q000008:administration & dosage / Q000031:analogs & derivatives*; D013997:Time Factors; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology; D018084:Ultrasonography, Interventional; D014654:Vascular Patency; D014945:Wound Healing / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; C117268:pimecrolimus; D016559:Tacrolimus