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.
OBJECTIVE
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.
Ormiston
John A
JA
Mercy Angiography, Auckland, New Zealand. johno@mercyangiography.co.nz
Webster
Mark W I
MW
Schwartz
Robert S
RS
Gladding
Patrick
P
Stewart
James T
JT
Kay
I Patrick
IP
Ruygrok
Peter N
PN
Hatrick
Robert
R
D000328:Adult; D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects / Q000295:instrumentation*; D000818:Animals; D002317:Cardiovascular Agents / Q000008:administration & dosage*; D020099:Coated Materials, Biocompatible; D017023:Coronary Angiography; D023903:Coronary Restenosis / Q000000981:diagnostic imaging / Q000209:etiology*; D023921:Coronary Stenosis / Q000000981:diagnostic imaging / Q000628:therapy*; D004195:Disease Models, Animal; D054855:Drug-Eluting Stents; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D006965:Hyperplasia; D008297:Male; D008875:Middle Aged; D009520:New Zealand; D011108:Polymers; D011446:Prospective Studies; D011474:Prosthesis Design; D012042:Registries; D018570:Risk Assessment; D012720:Severity of Illness Index; D013552:Swine; D016559:Tacrolimus / Q000008:administration & dosage / Q000031:analogs & derivatives*; D013997:Time Factors; D016896:Treatment Outcome; D018084:Ultrasonography, Interventional; D014992:Xylenes
D002317:Cardiovascular Agents; D020099:Coated Materials, Biocompatible; D011108:Polymers; D014992:Xylenes; C011055:parylene; C117268:pimecrolimus; D016559:Tacrolimus