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Evaluation of a Novel Slow-Release Paclitaxel-Eluting Stent With a Bioabsorbable Polymeric Surface Coating

Refat Jabara, MD^_*,_*, Nicolas Chronos, MD, FACC^_*, Damian Conway, MSc^,1, Warner Molema, PhD^,1, Keith Robinson, PhD, FACC^_*

^_* Saint Joseph’s Cardiovascular Research Institute/Saint Joseph’s Hospital of Atlanta, Georgia
DISA Vascular Ltd., Cape Town, South Africa.

^_* Reprint requests and correspondence: Dr. Refat Jabara, Saint Joseph’s Cardiovascular Research Institute, Saint Joseph’s Hospital of Atlanta, 5673 Peachtree Dunwoody Road, Suite 675, Atlanta, Georgia 30342. (Email: rjabara{at}sjha.org).

Objectives: We sought to evaluate a new second-generation drug-eluting stent (DES), comprising a slow-release biodegradable polylactide coglycolide (PLGA) polymer and low-dose paclitaxel on a thin-strut cobalt chromium stent platform, in a clinically relevant animal model.

Background: Our previous work demonstrated subacute vascular toxicity and necrosis triggering late excess neointima in pig coronaries, with a moderate paclitaxel dose eluted from an erodible polymer. The use of slower-releasing absorbable polymers with lower doses of paclitaxel is expected to minimize such adverse outcomes.

Methods: Three types of stents were implanted in pig coronary arteries using quantitative coronary angiography to optimize stent apposition: bare-metal stents (BMS); absorbable, slow-release polymer-coated-only stents (POLY); and absorbable polymer-based paclitaxel-eluting stents (PACL). The dose density of paclitaxel was 0.15 µg/mm² with in vitro studies demonstrating a gradual elution over the course of 12 to 16 weeks. Animals underwent angiographic restudy and were terminated at 1 and 3 months for complete histopathologic and histomorphometric analyses.

Results: At 1 month, intimal thickness varied significantly according to stent type, with the lowest level for the PACL group compared with the BMS and POLY groups (0.06 ± 0.02 mm vs. 0.17 ± 0.07 mm, 0.17 ± 0.08 mm, respectively, p < 0.001); histological percent area stenosis was 18 ± 4% for PACL compared with 27 ± 7% for BMS and 30 ± 12% for POLY, respectively (p = 0.001). At 3 months, PACL showed similar neointimal thickness as BMS and POLY (0.09 ± 0.05 mm vs. 0.13 ± 0.10 mm and 0.11 ± 0.03 mm respectively, p = 0.582). Histological percent area stenosis was 23 ± 8% for PACL versus 23 ± 11% for BMS and 23 ± 2% for POLY, respectively (p = 1.000).

Conclusions: This study shows favorable vascular compatibility and efficacy for a novel DES that elutes paclitaxel in porcine coronary arteries. These results support the notion that slowing the release rate and lowering the dose of paclitaxel favorably influences the vascular biological response to DES implant, decreasing early toxicity and promoting stable healing while still suppressing neointima formation.

Abbreviations and Acronyms   ANOVA = analysis of variance   BMS = bare-metal stent(s)   DES = drug-eluting stent(s)   EEL = external elastic lamina   IEL = internal elastic lamina   PACL = polymer-based paclitaxel-eluting stent(s)   PLGA = polylactide coglycolide   POLY = polymer-only-coated stent(s)