zotarolimus and Atherosclerosis

Delayed healing and endothelial dysfunction may occur with drug-eluting stents (DES), promoting accelerated infiltration of lipids in the neointima and development of neoatherosclerosis (NA). Pathology data suggest durable polymer (DP) of DES to play a major role in this process. Whether biodegradable polymer (BP) may address these issues is uncertain. We compared in vivo vessel healing and NA of current generation BP- or DP-DES using serial optical coherence tomography (OCT) assessments.. Ninety patients with multivessel coronary artery disease were randomized 1:1 to BP everolimus-eluting stents (EES, Synergy) or DP zotarolimus-eluting stents (ZES, Resolute Integrity). Co-primary endpoints were the maximum length of uncovered struts at 3 months (powered for non-inferiority) and the percentage of patients presenting with frames of NA at 18 months (powered for superiority) as measured by OCT. The maximum length of uncovered struts at 3 months was 10 ± 8 mm in the BP-EES group and 11 ± 7 mm in the DP-ZES group (mean difference -1 mm; upper 97.5% confidence interval +2 mm; P = 0.05 for non-inferiority; P = 0.45 for superiority). The percentage of patients presenting with frames of NA at 18 months was low and similar between BP-EES and DP-ZES groups (11.6% vs. 15.9%; P = 0.56). There was no stent thrombosis in both groups at 24 months.. BP-EES and DP-ZES showed a similar healing response at 3 months and a low incidence of NA at 18 months. Biocompatible polymers, regardless of whether they are durable or biodegradable, may favourably impact the long-term vascular response to current-generation DES.

Topics: Absorbable Implants; Aged; Atherosclerosis; Biocompatible Materials; Coronary Artery Disease; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Sirolimus; Time Factors; Tomography, Optical Coherence; Wound Healing

Drug-eluting stents (DES) have reduced late loss and target lesion revascularization through the inhibition of neointimal hyperplasia, but instead increased the risk of very late stent failure due to incomplete neointimal coverage and neoatherosclerosis. Although newer DES are more effective and safer than the first-generation DES, the difference in the condition of the stented lesions between Resolute zotarolimus-eluting stents (R-ZES) and Endeavor zotarolimus-eluting stents (E-ZES) on angioscopy has not been reported.. Consecutive patients who received R-ZES (n=46) or E-ZES (n=46) for de novo lesion of native coronary artery and had 1-year follow-up angioscopy were examined. Yellow color (grade 0-3), neointimal coverage (grade 0-2), heterogeneity score (maximum-minimum neointimal coverage grade) and thrombus (presence or absence) at stented lesion were evaluated. The maximum yellow color grade (1.2±0.9 vs. 0.7±1.0, P=0.005) was higher in R-ZES than in E-ZES. The maximum (1.9±0.3 vs. 1.5±0.5, P<0.001) and minimum (1.1±0.7 vs. 0.4±0.5, P<0.001) coverage grade was higher in E-ZES than in R-ZES. The heterogeneity score was higher in R-ZES than in E-ZES (1.0±0.5 vs. 0.7±0.7, P=0.007). Prevalence of thrombus was not different between the 2 stents (6.5% vs. 2.2%, P=0.4).. E-ZES had better neointimal coverage with less yellow plaque and lower heterogeneity score than R-ZES. The lesions with E-ZES appeared more stable than those with R-ZES. (Circ J 2016; 80: 650-656).

Topics: Aged; Angioscopy; Atherosclerosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neointima; Plaque, Atherosclerotic; Sirolimus

To assess the late postinterventional response to iliac stenting in atheromatous rabbits using the Xience V everolimus-eluting stent (Xience V EES; Abbott Vascular) and the Resolute zotarolimus-eluting stent (Resolute ZES; Medtronic Vascular) with the MultiLink Vision bare metal stent (BMS; Abbott Vascular) as a reference.. Xience V EES and Resolute ZES were developed to overcome shortcomings of first-generation DES.. Functional and microscopic changes were assessed by organ bath experiments and histopathologic examination. Gene expression was investigated using RT-PCR.. After 91 days, re-endothelialization was nearly complete (BMS: 93 ± 3%; Resolute ZES: 92 ± 2%; Xience V EES: 94 ± 3%; P = 0.10). Neointima thickness was similar in Resolute ZES (0.17 ± 0.08 mm) and BMS (0.17 ± 0.09 mm), and reduced in Xience V EES (0.03 ± 0.01 mm; P < 0.0001). Xience V EES had less peri-strut inflammation compared with BMS (P = 0.001) and Resolute ZES (P = 0.0001), while arterial segments distal to Xience V EES were more sensitive to acetylcholine than those distal to BMS and Resolute ZES (P = 0.02). Lectin-like oxidized receptor-1 was overexpressed in stented arteries (P < 0.001), whereas thrombomodulin was downregulated in Resolute ZES (P = 0.01) and BMS (P = 0.02) compared to unstented arteries of rabbits on regular chow. No significant changes were seen for vascular cell adhesion molecule-1, nitric oxide synthase 3, or endothelin-1.. At 3-month follow-up, nearly complete re-endothelialization was achieved for all stent groups. Xience V EES induced greater suppression of neointimal growth and peri-strut inflammation, higher vasorelaxation to acetylcholine, and expression of thrombomodulin at the level of unstented controls.

Topics: Acetylcholine; Angioplasty, Balloon; Animals; Atherosclerosis; Disease Models, Animal; Down-Regulation; Drug-Eluting Stents; Endothelium, Vascular; Everolimus; Iliac Artery; Inflammation; Neointima; Rabbits; Scavenger Receptors, Class E; Sirolimus; Thrombomodulin; Vasodilator Agents

To evaluate differences in strut coverage, inflammation and endothelialization between two second-generation polymer-based drug-eluting stents (DES) in an atherosclerotic rabbit double-injury iliac artery model at 28 days follow-up.. Rabbits with induced atheroma received bilateral iliac artery stents: everolimus-eluting stent (Xience V EES; Abbott Vascular), zotarolimus-eluting stent (Resolute ZES; Medtronic CardioVascular), or bare-metal stent (BMS; MultiLink Vision; Abbott Vascular). After 28 days, total neointimal coverage examined by scanning electron microscopy was >98% for all three stent types. Neointimal thickness above stent struts was decreased by 50% in Xience V EES (0.06 ± 0.01 mm; P = 0.00001) compared with BMS (0.15 ± 0.03 mm) and Resolute ZES (0.12 ± 0.04 mm). Luminal area was largest for Xience V EES (3.79 ± 0.33 mm(2) ; P = 0.0003 for Xience V EES vs. BMS), followed by Resolute ZES (3.46 ± 0.45 mm(2) ; P = 0.083 for Resolute ZES vs. BMS) and BMS (3.07 ± 0.53 mm(2) ). Percentage area stenosis was smallest for Xience V EES (17.23 ± 3.64%; P = 0.00001), while BMS (30.25 ± 7.48%) and Resolute ZES (30.79 ± 7.15%) did not differ. Endothelial monolayer regrowth was significantly lower in Resolute ZES (65 ± 13%) versus BMS (79 ± 11%; P = 0.004). There was no difference between Xience V EES (74 ± 10%) and BMS. Xience V EES was further associated with a lower number of inflammatory cells surrounding the stent struts (7 ± 2 per strut) in comparison to Resolute ZES (15 ± 6; P = 0.0001) and BMS (17 ± 9; P = 0.0005).. In this atherosclerotic rabbit model, Xience V EES suppressed neointimal thickening better, with normal endothelial regrowth as compared with BMS, and less strut-induced inflammation.

Topics: Angioplasty, Balloon; Animals; Atherosclerosis; Cardiovascular Agents; Cell Proliferation; Disease Models, Animal; Drug-Eluting Stents; Endothelial Cells; Everolimus; Iliac Artery; Inflammation; Male; Neointima; Prosthesis Design; Rabbits; Radiography; Sirolimus; Time Factors; Vascular System Injuries