Abstract 4715: The Balance Between Polymer Degradation and Drug Concentration Determines the Neointimal Response to Stents Eluting Tacrolimus From a Biodegradable Polymer Coating up to 1 Year Post Stenting
Introduction: Efficacy of drug eluting stents (DES) to reduce neointimal thickness (NIT) varies between clinical reports. Important contributors to this response are the anti-proliferative, anti-inflammatory effects of drugs and pro-inflammatory effects of coatings.
Hypothesis: efficacy of DES in reducing NIT is determined by the balance between positive drug effects versus irritant coating degradation effects.
Methods: We assessed in polylactide-polyglycolide-(PLGA)-Tacrolimus (T) eluting stents how such balance affects NIT in Yucatan swine up to 1 year post-stenting. We compared fast-degrading high dose T (TH, 2μg/mm2, N=21), slow-degrading low dose T (TL, 1μg/mm2, N=21) and slow-degrading PLGA-only stents (Pol, N=21) to BMS (N=14). Stents were implanted (stent/artery ratio: 1.1) in pre-injured (balloon/artery ratio: 1.1–1.3) coronary arteries. Animals were followed for 90 –365 days.
Results: At 90 days, PLGA degradation resulted in increased inflammation in Pol which was paralleled by an increased NIT. Both DES showed less inflammation and reduced NIT (P=0.05 BMS, POL vs TL, TH by ANOVA). At 180 days, the chronic irritation by the slow-degrading, low dose TL resulted in increased injury, inflammation and >50% NIT catch-up, becoming similar to Pol, while the already degraded, high dose TH and BMS showed a stable low NIT (P<0.05 BMS, TH vs Pol). At 1 year all stents showed a similar low NIT.
Conclusions: Tacrolimus can suppress the negative effects of PLGA degradation at high enough concentration. When the elution-degradation balance becomes unfavorable, the chronic irritant effects of coating degradation can outweigh the drug effects resulting in late catch-up.