Permanent and biodegradable polymer coatings in the absence of antiproliferative drugs in a porcine model of coronary artery stenting.

AIMS: The purpose of the present study was to examine the comparative vascular healing response to stents coated with permanent or biodegradable polymer and uncoated stents in a porcine model of coronary artery stenting. METHODS AND RESULTS: Juvenile pigs were randomly allocated to implantation of stents coated with permanent polymer (PP, methacrylate-based, n=10), biodegradable polymer (BP, poly-lactic acid-based, n=10) or bare metal control stents (n=10), in the absence of antiproliferative drugs. At 28 days, animals were sacrificed and specimens prepared for histopathologic assessment. Endothelialisation was complete in all treatment groups. Vascular injury at 28 days was greater in PP stents as compared with uncoated stents (p=0.05) though not as compared with BP-coated stents (p=ns). PP stents showed increased inflammatory scores compared with BP-coated (p=0.03) and uncoated stents (p=0.02). There was also greater neointimal growth with PP-coated stents compared with uncoated stents (p=0.02). CONCLUSIONS: In the absence of antiproliferative drugs, stents coated with methacrylate-based PP, but not with poly-lactic acid-based BP, provoked significant vessel wall inflammatory reactions resulting in greater vascular injury and increased neointimal growth compared with uncoated stents. Biodegradable polymer coatings may be considered preferable to facilitate drug elution with minimal vessel wall toxicity.

Histopathological comparison of biodegradable polymer and permanent polymer based sirolimus eluting stents in a porcine model of coronary stent implantation.

Biodegradable stent coatings were recently introduced as a potential solution to overcome sustained inflammatory responses observed with permanent polymer-based drug-eluting stents. In a preliminary study, selected biodegradable or permanent polymer-based sirolimus-eluting stent (SES) formulations were screened for effectiveness in comparison to bare metal stents (BMS) at 28 days. Subsequently, the most favourable SES formulation was compared to commercially available SES (Cypher™) at 28, 90 and 180 days to investigate the histopathologic response as well as tissue, blood and organ pharmacokinetics. Overlapping SES implantation was conducted to evaluate vascular healing at 28 days in this particular setting. SES with biodegradable poly (L-lactide) polymer (PLLA) or poly(lactide-co-glycolide) showed the most favourable outcome with regards to reductions in neointimal area in comparison to BMS at 28 days. The PLLA SES showed a similar reduction in neointimal area compared to Cypher™ at 28 days, with significant greater reductions at 90 and 180 days (1.7 ± 0.7 mm² vs. 3.1 ± 1.5 mm², p=0.03 and 1.8 ± 1.2 mm² vs. 3.0 ± 1.5 mm², p=0.01, respectively). Sirolimus vascular tissue concentrations were detectable up to 90 days following implantation. Overlapping stented segments showed favourable histopathologic results with respect to fibrin deposition and endothelialisation at 28 days. In conclusion, the use of PLLA as drug-eluting matrix resulted in mild inflammatory responses in the presence of effective sirolimus tissue concentrations. The greater efficacy observed at long-term follow-up in PLLA SES compared to Cypher™ may be a multifactorial result of stent design, polymer biocompatibility and improved release kinetics.

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.