Differences in vessel healing following delivery of everolimus or paclitaxel: a comparative experimental study using identical stent and biodegradable polymer platforms.
We aimed to compare the vascular effects exclusive to antiproliferative agents by using identical stent and biodegradable polymeric matrices eluting everolimus (BP-EES) (Carlo; Balton) and paclitaxel (BP-PES) (Luc-Chopin2; Balton) in the porcine model of coronary injury. A total of 37 stents were implanted with 110% overstretch in the coronary arteries of 14 domestic pigs: 13 BP-PES, 16 BP-EES and eight bare metal stents (BMS) (Chopin2; Balton). Coronary angiography was performed after 28 and 90 days, the animals were sacrificed and the stented segments harvested for histopathological evaluation. At 28 days, BP-PES most effectively limited angiographic late loss (LL PES: 0.15±0.1 vs. EES: 0.40±0.3 vs. BMS: 0.5±0.2 mm; p=0.04) and neointimal thickness (NT) in histology (PES: 0.12 [0.1-0.2] vs. EES: 0.38 [0.3-0.4] vs. BMS: 0.35 [0.3-0.4] mm; p<0.01). The BP-PES had lower endothelialisation (EES: 100% vs. PES: 40±4% vs. BMS: 97.5±5%; p<0.01) and slightly higher inflammation scores (EES: 1 vs. PES: 2.1±0.3 vs. BMS: 1; p<0.01). At three months, LL remained unchanged in the EES and BMS groups in contrast to an increase in the PES group (EES: 0.38±0.3 vs. PES: 0.52±0.4 vs. BMS: 0.51±0.3 mm; p=0.69). NT stabilised at 90 days in the EES group in comparison to a fourfold increase in the PES group and a 30% increase in the BMS group (EES: 0.35 [0.3-0.5] vs. PES: 0.53 [0.5-0.8] vs. BMS: 0.46 [0.4-0.5] mm: p=0.07). Stent endothelialisation and inflammation were comparable at 90 days in all groups. Temporal differences in vascular response were seen by the delivery of different antiproliferative agents. In contrast to everolimus, paclitaxel seems to induce a slightly higher degree of inflammation in the short term, potentially leading to further neointimal hyperplasia in the long term.
Center for Cardiovascular Research and Development of American Heart of Poland, Ustron, Poland.
Piotr P
PP
Buszman
Krzysztof
K
Milewski
Jacek
J
Pająk
Michał
M
Jelonek
Bartłomiej
B
Orlik
Agata
A
Krauze
Beata
B
Gwiazdowska-Nowotka
Wojciech
W
Wojakowski
Armando
A
Tellez
Juan F
JF
Granada
Paweł E
PE
Buszman
D020341:Absorbable Implants; D000818:Animals; D020099:Coated Materials, Biocompatible; D017023:Coronary Angiography; D003331:Coronary Vessels / Q000293:injuries* / Q000473:pathology*; D054855:Drug-Eluting Stents; D004730:Endothelium, Vascular / Q000187:drug effects*; D000068338:Everolimus; D006965:Hyperplasia; D007249:Inflammation / Q000473:pathology; D023421:Models, Animal; D058426:Neointima / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D011108:Polymers; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives; D015607:Stents; D013552:Swine
D020099:Coated Materials, Biocompatible; D011108:Polymers; D000068338:Everolimus; D017239:Paclitaxel; D020123:Sirolimus