zotarolimus and Neointima

Exaggerated neointimal hyperplasia is considered as the primary mechanism for increased restenosis in patients with diabetes mellitus (DM) treated with bare-metal stent. However, the vessel response in DM and non-DM treated with different drug-eluting stents (DES) has not been systematically evaluated.. We investigated 3D intravascular ultrasound (postprocedure and 6 to 9 months) in 971 patients (267 with DM and 704 without DM) treated with sirolimus- (n=104), paclitaxel- (n=303), zotarolimus- (n=391), or everolimus- (n=173) eluting stents. Volumetric data were standardized by length as volume index (VI). At postprocedure, lumen VI at the stented segment was significantly smaller in DM than in non-DM, whereas vessel VI was similar between the 2 groups. At follow-up, neointimal obstruction and maximum cross-sectional narrowing (neointimal area/stent area) were not significantly different between the 2 groups with no interaction for the DES type. Consequently, lumen VI was smaller in DM than in non-DM at follow-up. In the reference segments, residual plaque burden at postprocedure was significantly greater in DM than in non-DM, although change in lumen VI was similar between the 2 groups. The arterial responses at the reference segments also showed no interaction for the DES type.. DM and non-DM lesions showed similar vessel response in both in-stent and reference segments regardless of the DES type. In the DES era, the follow-up lumen in DM patients seems to be determined primarily by the smaller lumen at postprocedure rather than exaggerated neointima within the stent or plaque proliferation at the reference segments.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Diabetes Mellitus; Drug-Eluting Stents; Everolimus; Female; Humans; Hyperplasia; Linear Models; Male; Middle Aged; Multicenter Studies as Topic; Multivariate Analysis; Neointima; Paclitaxel; Predictive Value of Tests; Prosthesis Design; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Factors; Sirolimus; Time Factors; Treatment Outcome; Ultrasonography, Interventional

Durable polymers used in drug-eluting stents are considered a potential cause of hypersensitivity inflammatory response adversely affecting stent healing. Using a sequential follow-up with optical coherence tomography, we compared the differences in healing profiles of 2 drug-eluting stents with a biodegradable or durable polymer.. Sixty patients with multivessel disease were prospectively enrolled to receive both study stents, which were randomly assigned to 2 individual vessels, a Resolute Integrity zotarolimus-eluting stent with a durable BioLinx polymer and a BioMatrix NeoFlex Biolimus A9-eluting stent with a biodegradable polylactic acid polymer. Optical coherence tomography was performed at baseline, then in 5 randomly assigned monthly groups at 2 to 6 months, and at 9 months in all patients. The primary end point was the difference in optical coherence tomography strut coverage at 9 months. Key secondary end points included angiographic late lumen loss and composite major adverse cardiac events (cardiac death, myocardial infarction, target lesion revascularization, and definite or probable stent thrombosis) at 9 months. Resolute Integrity zotarolimus-eluting stent showed significantly better strut coverage than BioMatrix NeoFlex Biolimus A9-eluting stent at 2 to 6 months (. Despite having a durable polymer, Resolute Integrity zotarolimus-eluting stent exhibited better strut coverage than BioMatrix NeoFlex Biolimus A9-eluting stent having a biodegradable polymer; both showed similar antiproliferative efficacy. This novel, longitudinal, sequential optical coherence tomography protocol using each patient as own control could achieve conclusive results in small sample size.. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01742507.

Topics: Absorbable Implants; Aged; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Female; Hong Kong; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

Polymer coatings of drug-eluting stents (DES) may induce allergic reactions and inflammation, resulting in late-acquired stent malapposition (LASM) with the risk of stent thrombosis. This study evaluated, if biodegradable polymer (BP) reduces the incidence of LASM compared to permanent polymer (PP) after treatment with newer generation DES.. Fifty patients with 59 lesions were randomized (2:1) to elective treatment with second generation PP-DES (n = 32, 39 stents), either Everolimus-eluting or Zotarolimus-eluting stents, or with BP-DES (Biolimus-eluting stents [BES]; n = 18, 20 stents) and underwent optical coherence tomography directly after implantation and after 1 year. After implantation acute stent malappositions (ASM) were documented in 30 stents (51%) distributed to 22 stents treated with PP-DES (56%) and 8 with BP-DES (40%; n.s.). After 1 year, late stent malappositions (LSM) were detected in 14 stents (24 %); ASM persisted (APSM) in 9 stents after one year (7 PP-DES-18%, 2 BES-10%), whereas ASM resolved in 21 stents. In addition, LASM was documented in nine stents including five stents without and four stents with additional APSM. All LASM were located in PP-DES (n = 9; 23%), none in BP-DES (P = 0.022). Compared to the reference lumen area, in-stent lumen area of stents without LASM was smaller due to neointimal hyperplasia (P = 0.021), whereas in-stent lumen area at maximum LASM of stents with LASM was larger due to positive remodeling (P = 0.002).. In conclusion the use of BP-DES reduced the occurrence of LASM due to positive remodeling compared to second generation PP-DES.

Topics: Absorbable Implants; Aged; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Polymers; Postoperative Complications; Prospective Studies; Prosthesis Design; Prosthesis Failure; Sirolimus; Tomography, Optical Coherence; Treatment Outcome

Previous studies have suggested a benefit of cilostazol in addition to standard dual-antiplatelet therapy (DAPT), reducing in-stent late luminal loss and restenosis after percutaneous coronary intervention (PCI) with bare-metal and drug-eluting stent (DES) implantation. However, there is a paucity of intravascular ultrasound (IVUS) assessment of neointimal tissue hyperplasia (NIH) after triple-antiplatelet therapy (TAPT), especially in diabetic patients treated with DES.. This prospective, placebo-controlled trial was conducted in diabetic patients randomized (1:1) to receive either standard DAPT (aspirin and clopidogrel) vs TAPT with cilostazol for a minimum of 12 months after PCI with Endeavor zotarolimus-eluting stent (E-ZES). The primary endpoint was the 9-month comparison of percentage of NIH in both groups. Additionally, we compared in-stent late lumen loss, binary restenosis, major adverse cardiac event (MACE; cardiac death, non-fatal myocardial infarction, and restenosis) rates, and the incidence of vascular/bleeding complications.. In total, 133 diabetic patients were enrolled (cilostazol cohort = 65 patients) with 56.4% male and mean age of 60.8 years. Overall, the two cohorts were comparable in terms of baseline clinical and angiographic characteristics, except for the reference vessel diameter, which was smaller among patients randomized to cilostazol (2.48 ± 0.46 mm vs 2.69 ± 0.48 mm; P=.01). At 9 months, there was a non-significant trend toward less percentage of NIH obstruction in the TAPT cohort (33.2 ± 8.29% vs 35.1 ± 8.45%; P=.07). However, this finding did not impact angiographic late-lumen loss (0.60 ± 0.46 mm cilostazol group vs 0.64 ± 0.48 mm control group; P=.30) and binary restenosis (9.8% vs 6.8%; P=.99). MACE rate also did not significantly differ between the cohorts (13.8% cilostazol group vs 8.8% control group; P=.81). Of note, the addition of a third antiplatelet agent did not increase vascular and bleeding complications.. In diabetic patients treated with E-ZES, TAPT with cilostazol did not add any significant benefit in terms of NIH suppression or MACE reduction.

Topics: Aspirin; Cilostazol; Clopidogrel; Comorbidity; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Diabetes Mellitus; Drug Therapy, Combination; Drug-Eluting Stents; Female; Hemorrhage; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Sirolimus; Tetrazoles; Ticlopidine; Treatment Outcome

Incomplete neointimal coverage and malapposed struts after stenting are associated with increased risk of stent thrombosis. We aimed to evaluate neointimal coverage early after Resolute zotarolimus-eluting stent (R-ZES) implantation using optical coherence tomography (OCT). A total of 20 patients with de novo native coronary lesions with R-ZES were enrolled. Among these patients, 20 stented lesions in 19 patients were evaluated at 1, 2, and 3 months after R-ZES implantation. The strut apposition and neointimal coverage were evaluated by OCT. Neointimal hyperplasia (NIH) thickness and percentage of covered struts and the proportion of incompletely apposed struts were measured at 1-mm intervals. The mean percentages of covered stent struts were over 85 % within 3 months (88.4 ± 6.3 % at 1 month, 95.5 ± 5.5 % at 2 months, 93.6 ± 3.5 % at 3 months). The percentages of incompletely apposed struts were not significantly different among the groups (4.4 ± 4.2 % at 1 month, 1.9 ± 1.9 % at 2 months, 3.1 ± 2.2 % at 3 months, p = 0.51). Mean NIH thickness (38.9 ± 8.1 μm at 1 month, 70.6 ± 18.8 μm at 2 months, 54.1 ± 5.9 at 3 months, p = 0.0016) was thickest in the 2 months group. Most of all OCT findings within 2 months demonstrated neointimal coverage with low signal intensity. The neointimal coverage of ZES-R was over 85 % within 3 months. These data may support shorter requirement of dual antiplatelet therapy duration with R-ZES.

Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Coronary Restenosis; Coronary Stenosis; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Japan; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Predictive Value of Tests; Prospective Studies; Risk Factors; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

To compare the efficacy and safety of the MiStent absorbable polymer sirolimus-eluting stent (APSES) with a zotarolimus-eluting stent (ZES).. The trial was a 2:1 randomisation at 26 sites of 184 patients implanted with an APSES (n=123) versus a ZES (n=61). Following stent implantation, all patients underwent quantitative coronary angiography at baseline and at nine months of follow-up, while a select subgroup also underwent optical coherence tomography (OCT). The primary efficacy hypothesis was superiority of in-stent late lumen loss (LLL) of APSES compared to ZES. At nine months, the primary endpoint was met, with a mean in-stent LLL of 0.27±0.46 mm in 103 APSES patients versus 0.58±0.41 mm in 52 ZES patients (p<0.001). The proportion of uncovered stent struts by OCT at nine months was very low in both groups. The mean neointimal thickness of covered struts (p=0.002) and percent net volume obstruction (p≤0.003) were significantly lower in the APSES than in the ZES group. Major adverse cardiac event and stent thrombosis rates were low and comparable between groups.. The DESSOLVE II trial demonstrated superiority in the primary efficacy endpoint of nine-month mean LLL for APSES compared to ZES. Strut coverage by OCT was high with both stents and the clinical safety endpoints including stent thrombosis were equally low in both groups. ClinicalTrials.gov Identifier: NCT01294748.

Topics: Absorbable Implants; Aged; Antibiotics, Antineoplastic; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Polymers; Single-Blind Method; Sirolimus; Tomography, Optical Coherence; Treatment Outcome

The aim of this study was to evaluate the extent of neointimal response after the implantation of a second-generation drug-eluting stent, zotarolimus-eluting stent (ZES-ER, Endeavor Resolute) or everolimus-eluting stent (EES, Xience V), using intravascular ultrasound (IVUS) in diabetic patients.. In all, 154 diabetic patients with de-novo coronary lesions were randomized to be implanted with a ZES-ER or EES, and the angiographic follow-up at 9 months combined with a complete IVUS study was available for 96 patients with 101 lesions.. Baseline demographic and lesion parameters were similar in both groups at index percutaneous coronary intervention. On follow-up angiography, in-stent late lumen loss and minimal lumen diameter were not different between the two groups. On IVUS study, neointimal hyperplasia volume [median (interquartile range): ZES-ER vs. EES; 2.25 mm (0.57-6.25) vs. 1.59 mm (0.45-8.37), P=0.615] and in-stent percentage of volume obstruction [median (interquartile range): ZES-ER vs. EES; 1.16% (0.33-3.61) vs. 0.77% (0.29-4.01), P=0.615] showed similar results between the two groups.. In diabetic patients, the second-generation drug-eluting stents, ZES-ER and EES, were comparable in inhibiting neointimal proliferation.

Topics: Aged; Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Diabetic Angiopathies; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Pilot Projects; Predictive Value of Tests; Prosthesis Design; Republic of Korea; Risk Factors; Sirolimus; Time Factors; Treatment Outcome; Ultrasonography, Interventional

Patients at high bleeding risk would benefit from a shorter dual antiplatelet therapy after PCI. Compared to first-generation devices, the design of newer generation drug-eluting stents may facilitate more rapid anatomical and functional healing of stented vessel based on thinner stent platforms, biodegradable/biocompatible polymers and rapid drug elution.. Forty-four non-diabetic patients with acute coronary syndrome (ACS) and culprit lesion in the LAD were randomized to receive either biodegradable polymer sirolimus-eluting stent (BP-SES) or durable polymer zotarolimus-eluting stent (DP-ZES). Neointimal strut coverage was examined using optical coherence tomography, and vasodilator response on invasive thermodilution-derived coronary flow reserve (CFR) at 3-month follow-up. The primary endpoints were percent uncovered struts and CFR. A total of 425 cross-sections (4,897 struts) were analyzed in the BP-SES group, and 425 cross-sections (5,467 struts) in the DP-ZES group. The percent uncovered struts was lower in the BP-SES group compared with the DP-ZES group, both at strut level (3.9% vs. 8.9%, respectively, P<0.001), and stent level (3.9 ± 3.2% vs. 8.9 ± 6.9%, respectively, P=0.019). No significant difference was found between the 2 groups regarding CFR (3.0 ± 1.3 vs. 3.2 ± 1.0, respectively, P>0.05).. In non-diabetic patients with ACS, BP-SES provided slightly better stent strut coverage at 3 months compared with DP-ZES, but neither stent was fully covered. No difference in vasodilator response was seen.

Topics: Absorbable Implants; Acute Coronary Syndrome; Aged; Biodegradable Plastics; Double-Blind Method; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Prospective Studies; Sirolimus; Vasodilation

This study sought to assess device-specific outcomes after implantation of bare-metal stents (BMS), zotarolimus-eluting Endeavor Sprint stents (ZES-S), paclitaxel-eluting stents (PES), or everolimus-eluting stents (EES) (Medtronic Cardiovascular, Santa Rosa, California) in all-comer patients undergoing percutaneous coronary intervention.. Few studies have directly compared second-generation drug-eluting stents with each other or with BMS.. We randomized 2,013 patients to BMS, ZES-S, PES, or EES implantation. At 30 days, each stent group received up to 6 or 24 months of clopidogrel therapy. The key efficacy endpoint was the 2-year major adverse cardiac event (MACE) including any death, myocardial infarction, or target vessel revascularization, whereas the cumulative rate of definite or probable stent thrombosis (ST) was the key safety endpoint.. Clinical follow-up at 2 years was complete for 99.7% of patients. The MACE rate was lowest in EES (19.2%; 95% confidence interval [CI]: 16.0 to 22.8), highest in BMS (32.1%; 95% CI: 28.1 to 36.3), and intermediate in PES (26.2%; 95% CI: 22.5 to 30.2) and ZES-S (27.8%; 95% CI: 24.1 to 31.9) groups (chi-square test = 18.9, p = 0.00029). The 2-year incidence of ST in the EES group (1%; 95% CI: 0.4 to 2.2) was similar to that in the ZES-S group (1.4%; 95% CI: 0.7 to 2.8), whereas it was lower compared with the PES (4.6%, 95% CI: 3.1 to 6.8) and BMS (3.6%; 95% CI: 2.4 to 5.6) groups (chi-square = 16.9; p = 0.0001).. Our study shows that cumulative MACE rate, encompassing both safety and efficacy endpoints, was lowest for EES, highest for BMS, and intermediate for PES and ZES-S groups. EES outperformed BMS also with respect to the safety endpoints with regard to definite or probable and definite, probable, or possible ST. (PROlonging Dual antiplatelet treatment after Grading stent-induced Intimal hyperplasia studY [PRODIGY]; NCT00611286).

Topics: Aged, 80 and over; Chi-Square Distribution; Clopidogrel; Coronary Restenosis; Coronary Thrombosis; Drug Administration Schedule; Drug Therapy, Combination; Drug-Eluting Stents; Everolimus; Female; Humans; Hyperplasia; Italy; Kaplan-Meier Estimate; Male; Metals; Middle Aged; Myocardial Infarction; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prosthesis Design; Risk Factors; Sirolimus; Stents; Ticlopidine; Time Factors; Treatment Outcome

To our knowledge, no randomised study has compared rates of uncovered stent struts in everolimus (EES) vs. new-generation zotarolimus-eluting (ZES-R) stents in acute coronary syndrome (ACS). The aim of our study was to evaluate the completeness of neointimal coverage with optical coherence tomography (OCT) in ACS patients treated with drug-eluting stents (DES) comparing EES versus new-generation ZES-R.. All eligible ACS patients admitted to four Italian centres with a clinical indication for culprit lesion intervention were randomised 1:1 to EES or ZES-R. The primary study endpoint was the percentage of uncovered stent struts evaluated by optical coherence tomography (OCT) at six months. Secondary endpoints were the percentage of malapposed stent struts, percent neointimal hyperplasia cross-sectional area (CSA) and major adverse cardiac events (MACE) at six months. A total of 60 patients were randomised to EES (n=29) or ZES-R (n=31). No differences were observed in baseline characteristics between the two groups. Overall, 31.7% presented with STEMI, of which 68.4% were anterior. The other patients comprised 41.7% NSTEMI and 26.7% troponin-negative ACS. A mean of 1.3±0.6 lesions were treated per patient, with a mean of 1.3±0.5 stents per lesion. At 30 days there was one sudden death. Six-month OCT analysis was performed in 25 lesions in the EES group and in 24 lesions in the ZES-R group. There was no difference in the primary endpoint of uncovered stent struts between groups (EES 6.42% [3.27, 9.57] vs. ZES-R 7.07% [3.22, 10.92]; p=0.80). Furthermore, there were no differences between groups in the percentage of malapposed stent struts, either with (EES 1.19% [0.34, 2.04] vs. ZES-R 0.85% [0.40, 1.30]; p=0.49) or without coverage (EES 1.06% [0.12, 2.01] vs. ZES-R 0.24% [0.05, 0.44]; p=0.09). Percent neointima CSA was similar in both groups (EES 37.0% [18.6, 55.3] vs. ZES-R 26.6% [18.4, 34.8]; p=0.31). At six-month clinical follow-up, no additional patients died or suffered MI. There were four MACE in the EES group and one in the ZES-R group.. In our study, in patients presenting with ACS, both EES and ZES-R had low percentages of malapposed and uncovered stent struts at six-month OCT analysis.

Topics: Acute Coronary Syndrome; Aged; Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Single-Blind Method; Sirolimus; Tomography, Optical Coherence

The ZOMAXX I trial tested the noninferiority of a zotarolimus-eluting coronary stent (ZoMaxx(™) ) when compared with a paclitaxel-eluting coronary stent (Taxus(™) Express(2™) ) in a randomized trial of percutaneous intervention for de novo coronary artery stenosis. Angiographic analysis at the primary endpoint of 9 months has been reported previously. The purpose of this follow-on analysis was to describe the clinical results of the ZoMaxx and Taxus cohorts of the ZOMAXX I trial after 5 years.. In the ZOMAXX I trial, 199 patients received a ZoMaxx stent and 197 patients received a Taxus stent at 29 investigative sites in Europe, Australia, and New Zealand. The two groups were generally well matched with respect to both clinical and lesional characteristics, including the incidence of diabetes (ZoMaxx 22% vs. Taxus 26%; P = 0.29), reference vessel diameter (ZoMaxx 2.79 ± 0.43 mm vs. Taxus 2.81 ± 0.46 mm; P = 0.65), and lesion length (ZoMaxx 14.9 ± 5.7 mm vs. Taxus 14.6 ± 5.5; P = 0.61). Through 5 years of follow-up, a total of 21 patients had died, six patients had withdrawn, nine had been lost to follow-up, and 13 missed their 5-year visit, leaving a total of 347 patients for analysis (169 ZoMaxx and 178 Taxus). At the 5-year time point, there were no significant differences in any clinical metric including ischemia-driven target lesion revascularization (TLR; ZoMaxx 10.6% vs. Taxus 7.1%; P = 0.29), Q-wave myocardial infarction (ZoMaxx 1.5% vs. Taxus 1.0%; P = 0.99), definite/probable stent thrombosis (ZoMaxx 1.5% vs. Taxus 3.0%; P = 0.34), and cardiac death (ZoMaxx 3.0% vs. Taxus 1.0%; P = 0.28).. After 5 years, the differences in clinical outcome between patients treated with ZoMaxx vs. Taxus stents did not reach statistical significance. However, the nominally higher rate of ischemia-driven TLR (10.6 vs. 7.1%) and the previously reported higher rate of restenosis after 9 months suggest that the ZoMaxx stent afforded less neointimal inhibition when compared with Taxus. © 2013 Wiley Periodicals, Inc.

Topics: Aged; Australia; Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Coronary Thrombosis; Drug-Eluting Stents; Europe; Female; Humans; Male; Middle Aged; Myocardial Infarction; Neointima; New Zealand; Paclitaxel; Percutaneous Coronary Intervention; Prosthesis Design; Risk Factors; Severity of Illness Index; Sirolimus; Time Factors; Treatment Outcome

Everolimus-eluting stents (EES) have shown favorable clinical outcomes. However, there have been no studies evaluating early vascular response after EES implantation. We designed a prospective study to compare the neointimal response between zotarolimus-eluting stents (ZES) and EES at 3 and 12 months using serial optical coherence tomography examinations.. Sixty patients who underwent 3-month and 12-month follow-up optical coherence tomography (36 EES, 24 ZES) were included. Neointimal coverage and malapposition were evaluated using a strut-based analysis at both 3 and 12 months. Neointimal hyperplasia area and thrombus were assessed. ZES showed a higher incidence of covered struts (81.5 vs. 77.1%, P<0.0001) and lower incidence of malapposed struts (1.4 vs. 2.3%, P=0.001) than EES at 3 months. However, at 12 months, EES showed a slightly higher incidence of covered struts (96.4 vs. 93.6%, P<0.0001) and a lower incidence of malapposed struts (0.9 vs. 1.1%, P=0.03) than ZES. Neointimal hyperplasia area was greater in the ZES group than in the EES group at both 3 and 12 months (0.77 vs. 0.49 mm, P=0.03 and 1.50 vs. 0.97 mm, P=0.01, respectively). No significant difference in the incidence of thrombus was observed at both 3 and 12 months.. ZES showed rapid neointimal healing compared with EES at 3 months. However, at 12 months, EES had a slightly better vascular healing profile than ZES.

Topics: Aged; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Hyperplasia; Male; Middle Aged; Neointima; Observer Variation; Odds Ratio; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Reproducibility of Results; Republic of Korea; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

Histologic experimental studies have reported incomplete neointimal healing in overlapping with respect to nonoverlapping segments in drug-eluting stents (DESs), but these observations have not been confirmed in human coronary arteries hitherto. On the contrary, angiographic and optical coherence tomography studies suggest that DES overlap elicits rather an exaggerated than an incomplete neointimal reaction.. Optical coherence tomography studies from 2 randomized trials including sirolimus-eluting, biolimus-eluting, everolimus-eluting, and zotarolimus-eluting stents were analyzed at 9- to 13-month follow-up. Coverage in overlapping segments was compared versus the corresponding nonoverlapping segments of the same stents, using statistical pooled analysis.. Forty-two overlaps were found in 31 patients: 11 in sirolimus-eluting stents, 3 in biolimus-eluting stents, 17 in everolimus-eluting stents, and 11 in zotarolimus-eluting stents. The risk ratio of incomplete coverage was 2.35 (95% CI 1.86-2.98) in overlapping versus nonoverlapping segments. Thickness of coverage in overlaps was only 85% (95% CI 81%-90%) of the thickness in nonoverlaps. Significant heterogeneity of the effect was observed, especially pronounced in the comparison of thickness of coverage (I(2) = 90.31).. The effect of overlapping DES on neointimal inhibition is markedly heterogeneous: on average, DES overlap is associated with more incomplete and thinner coverage, but in some cases, the overlap elicits an exaggerated neointimal reaction, thicker than in the corresponding nonoverlapping segments. These results might help to understand why overlapping DES is associated with worse clinical outcomes, both in terms of thrombotic phenomena and in terms of restenosis and revascularization.

Topics: Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Feasibility Studies; Female; Follow-Up Studies; Humans; Hyperplasia; Immunosuppressive Agents; Male; Middle Aged; Neointima; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

To evaluate long-term patterns of luminal changes after implantation of different types of drug-eluting stents (DES), we analyzed the serial angiographic outcomes of patients implanted with zotarolimus-eluting stents (ZES), sirolimus-eluting stents (SES), or paclitaxel-eluting stents (PES).. Little is known regarding long-term luminal changes after DES implantation.. As a subgroup analysis of the ZEST trial, we performed complete angiographic evaluation immediately after the procedure and at 9 months and 2 years in 111 patients with 165 lesions (36 patients with ZES, 40 with SES, and 35 with PES).. Baseline clinical, angiographic, and procedural characteristics were similar among the three groups. Quantitative angiographic analysis revealed significant decreases in minimal luminal diameter 9 months after stent implantation in the ZES (from 2.71 ± 0.49 to 2.21 ± 0.42 mm, P < 0.001), SES (from 2.79 ± 0.49 to 2.58 ± 0.57 mm, P < 0.001), and PES (from 2.66 ± 0.45 to 2.19 ± 0.52 mm, P < 0.001) groups. However, significant late improvements with different degree in luminal diameter were observed between 9 months and 2 years in the ZES (from 2.21 ± 0.42 to 2.39 ± 0.58 mm, P = 0.001), SES (from 2.58 ± 0.57 to 2.66 ± 0.60 mm, P = 0.039), and PES (from 2.19 ± 0.52 to 2.43 ± 0.52 mm, P < 0.001) groups.. Serial angiographic follow-up study revealed a biphasic luminal response after DES implantation, characterized by an early progression phase for the first 9 months and a late regression phase from 9 months to 2 years.

Topics: Aged; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Linear Models; Male; Middle Aged; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Republic of Korea; Single-Blind Method; Sirolimus; Time Factors; Treatment Outcome

There have been no optical coherence tomographic (OCT) data directly comparing the pattern of strut coverage between the 2 second-generation drug-eluting stents in the early period. The aim of this prospective study was to evaluate early strut coverage using optical coherence tomography 3 months after Resolute zotarolimus-eluting stent (ZES-R) or everolimus-eluting stent (EES) implantation in de novo coronary artery lesions. A total of 40 patients who were suitable for the OCT procedure and consented to the study protocol were randomized 1:1 to receive either ZES-R or EES. Among these patients, 35 stented lesions (18 ZES-R, 17 EES) in 34 patients were evaluated by optical coherence tomography immediately and 3 months after stent implantation. Neointimal hyperplasia thickness, percentage of uncovered struts, and the proportion of malapposed struts were measured at 1-mm intervals. An uncovered strut was defined as having a neointimal hyperplasia thickness of 0 μm. At the 3-month OCT evaluation, mean neointimal hyperplasia thickness (ZES-R vs EES 74 ± 41 vs 75 ± 35 μm, p = 0.89) and mean percentage of uncovered struts (ZES-R vs EES 6.2 ± 6.9 vs 4.7 ± 5.1%, p = 0.62) were not significantly different between the groups. The percentage of malapposed struts was also similar between the groups (0.7 ± 2.2% for ZES-R and 0.7 ± 1.7% for EES, p = 0.64). Thrombi were documented in 3 stents (1 [5.6%] in a ZES-R vs 2 [11.8%] in EES, p = 0.60). In conclusion, early stent strut coverage on the basis of serial OCT evaluation was comparable between ZES-R and EES 3 months after stent implantation.

Topics: Aged; Antineoplastic Agents; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Neointima; Prospective Studies; Sirolimus; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

Polymer formulation may affect the efficacy of drug-eluting stents. Resolute, Endeavor, and ZoMaxx are zotarolimus-eluting stents with different stent platforms and different polymer coatings and have been tested in clinical trials. The aim of this analysis was to compare the efficacy of zotarolimus-eluting stents with different polymers.. Data were obtained from the first-in man trial or first randomized trials of each stent, The Clinical RESpOnse EvaLUation of the MedTronic Endeavor CR ABT-578 Eluting Coronary Stent System in De Novo Native Coronary Artery Lesions (RESOLUTE), Randomized Controlled Trial to Evaluate the Safety and Efficacy of the Medtronic AVE ABT-578 Eluting Driver Coronary Stent in De Novo Native Coronary Artery Lesions (ENDEAVOR II), and ZoMaxx I trials. Follow-up intravascular ultrasound analyses (8 to 9 months of follow-up) were possible in 353 patients (Resolute: 88, Endeavor: 98, ZoMaxx: 82, Driver: 85). Volume index (volume/stent length) was obtained for vessel, stent, lumen, peristent plaque, and neointima. Cross-sectional narrowing was defined as neointimal area divided by stent area (%). Neointima-free frame ratio was calculated as the number of frames without intravascular ultrasound-detectable neointima divided by the total number of frames within the stent. At baseline, vessel, lumen, and peristent plaque volume index were not significantly different among the 4 stent groups. At follow-up, percent neointimal obstruction was significantly lower in Resolute compared with Endeavor, ZoMaxx, and Driver (Resolute: 3.7±4.0, Endeavor: 17.5±10.1, ZoMaxx: 14.6±8.1, Driver: 29.4±17.2%; P<0.001). Greater maximum cross-sectional narrowing and higher neointima-free frame ratio, suggesting less neointimal coverage, were observed in Resolute compared with other stent groups. Multiple regression analysis confirmed that the biodurable polymer used in Resolute independently correlated with neointimal suppression among 3 zotarolimus-eluting stents.. The different polymer formulations significantly affect the relative amount of neointima for zotarolimus-eluting stents.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00248079.

Topics: Aged; Angioplasty, Balloon, Coronary; Cell Proliferation; Coronary Angiography; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Polymers; Regression Analysis; Sirolimus; Ultrasonography, Interventional

Telmisartan is a peroxisome proliferator-activated receptor-γ activator with potent anti-inflammatory and antiatherogenic effects. The authors compared the effects of telmisartan and valsartan on neointima volume, atherosclerosis progression and brachial-ankle pulse wave velocity (baPWV) after stenting in hypertensive type 2 diabetes.. This was a prospective, randomised, 8-month follow-up study that included patients with significant coronary stenosis who received telmisartan (n=36) or valsartan (n=37).. University hospital.. Neointima volume and atherosclerosis progression 10 mm proximal and distal to the stented segment were analysed using repeat intravascular ultrasonography. baPWV and inflammatory markers such as interleukin 6, tumour necrosis factor α, C-reactive protein and adiponectin were compared.. Neointima volume at 8 months was significantly lower in the telmisartan group than the valsartan group (1.9±1.0 vs 2.6±1.4 mm(3)/1 mm, p=0.007, respectively). Total plaque volumes 10 mm proximal (7.1±1.5 vs 7.8±1.6 mm(3)/1 mm, p=0.032, respectively) and distal (3.5±1.4 vs 4.1±1.3 mm(3)/1 mm, p=0.028, respectively) to the stent were significantly lower in the telmisartan group than the valsartan group at 8 months. The decrease from baseline in baPWV was significantly greater in the telmisartan group than the valsartan group (-52±104 vs 30±113 cm/s, p=0.002, respectively). The increase from baseline in adiponectin levels and the decreases from baseline in interleukin 6 and tumour necrosis factor α levels were significantly greater in the telmisartan group at 8 months. Retinol-binding protein-4, homeostasis model of assessment index, hemoglobin A(1c) and low-density lipoprotein cholesterol levels decreased significantly in both groups without differences in changes from baseline between the two groups.. Telmisartan reduced neointima volume; atherosclerosis progression 10 mm proximal and distal to the stented segment and baPWV independent of blood pressure, glucose and lipid control in hypertensive type 2 diabetes. Clinical trial no NCT00599885 (clinicaltrials.gov.).

Topics: Adiponectin; Aged; Ankle Brachial Index; Anti-Inflammatory Agents; Benzimidazoles; Benzoates; C-Reactive Protein; Coronary Stenosis; Diabetes Mellitus, Type 2; Disease Progression; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Hypertension; Interleukin-6; Male; Middle Aged; Neointima; Prospective Studies; Single-Blind Method; Sirolimus; Telmisartan; Tetrazoles; Time Factors; Treatment Outcome; Tumor Necrosis Factor-alpha; Ultrasonography, Interventional; Valine; Valsartan

Patients with diabetes mellitus have increased risk of in-stent restenosis after coronary stent implantation due to neointimal hyperplasia (NIH). The aim of this study was to use quantitative coronary angiography (QCA) and volumetric intravascular ultrasound (IVUS) to evaluate the effects of the sirolimus-eluting Cypher® stent (SES) and the zotarolimus-eluting Endeavor® stent (ZES) on angiographic late lumen loss and intima hyperplasia in diabetic patients.. In the DiabeDES III trial, 127 patients were randomised to SES or ZES stent implantation. Angiographic 10-month follow-up data were available in 105 patients, including 48 SES and 57 ZES treated patients. Angiographic endpoints were in-stent late lumen loss and minimal lumen diameter. IVUS endpoints included NIH volume and in-stent percent volume obstruction. Baseline clinical characteristics and lesion parameters were similar in the two groups. At 10-month follow-up, angiographic in-stent late lumen loss (0.14±0.37 mm vs. 0.74±0.45 mm, p<0.001) was reduced and minimum lumen diameter was higher (2.36±0.53 mm vs. 1.96±0.65, p<0.001) in the SES group as compared to the ZES group. As compared to the ZES group, NIH volume was significantly reduced in the SES group (median [interquartile range]: 0.0 mm3 [0.0 to 1.2] vs. 16.5 mm3 [6.2 to 31.1], p<0.001). In-stent% volume obstruction was significantly reduced in SES as compared to ZES (median [interquartile range]: 0.0% [0.0-0.7] vs. 13.0% [6.7-20.8], p<0.001).. In diabetic patients, the SES reduced angiographic late lumen loss and inhibited NIH more effectively than ZES.

Topics: Aged; Angioplasty, Balloon, Laser-Assisted; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Diabetes Complications; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Hyperplasia; Male; Middle Aged; Neointima; Risk Factors; Single-Blind Method; Sirolimus; Treatment Outcome; Ultrasonography, Interventional

Inconsistent results in outcomes have been observed between the genders after drug-eluting stent implantation. The aim of this study was to investigate gender differences in neointimal proliferation for the Endeavor zotarolimus-eluting stent (ZES) and the Driver bare-metal stent (BMS). A total of 476 (n = 391 ZES, n = 85 BMS) patients whose volumetric intravascular ultrasound analyses were available at 8-month follow-up were studied. At 8 months, neointimal obstruction and maximum cross-sectional narrowing (CSN) were significantly lower in women than in men receiving ZES (neointimal obstruction 15.5 ± 9.5% vs 18.2 ± 10.9%, p = 0.025; maximum CSN 30.3 ± 13.2% vs 34.8 ± 15.0%, p = 0.007). Conversely, these parameters tended to be higher in women than in men receiving BMS (neointimal obstruction 36.3 ± 15.9% vs 27.5 ± 17.2%, p = 0.053; maximum CSN 54.3 ± 18.6% vs 45.6 ± 18.3%, p = 0.080). There was a significant interaction between stent type and gender regarding neointimal obstruction (p = 0.001) and maximum CSN (p = 0.003). Multivariate linear regression analysis revealed that female gender was independently associated with lower neointimal obstruction (p = 0.027) and maximum CSN (p = 0.004) for ZES but not for BMS. Compared to BMS, ZES were independently associated with a reduced risk for binary restenosis in both genders (odds ratio for women 0.003, p = 0.001; odds ratio for men 0.191, p <0.001), but the magnitude of this risk reduction with ZES was significantly greater in women than men (p = 0.015). In conclusion, female gender is independently associated with decreased neointimal hyperplasia in patients treated with ZES. The magnitude of risk reduction for binary restenosis with ZES is significantly greater in women than in men.

Topics: Angioplasty, Balloon, Coronary; California; Coronary Restenosis; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Hyperplasia; Male; Middle Aged; Myocardial Infarction; Neointima; Prognosis; Prosthesis Design; Retrospective Studies; Risk Factors; Sex Distribution; Sex Factors; Sirolimus

The Resolute stent is a newly developed system with a bio-histocompatible polymer that allows programmed drug delivery up to 180 days. The aim of this intravascular ultrasound (IVUS) analysis was to evaluate the short- (4 months) and mid-term (9 months) efficacy using the Resolute stent.. Data were derived from the RESOLUTE trial, a prospective, multicenter, non-randomized, single-arm study to treat de novo native coronary artery lesions. This trial included 2 cohorts with different follow-up periods, and all enrollment patients in this trial received IVUS study. Follow-up IVUS was available in 24 patients (4-month group) and 88 patients (9-month group). Neointimal obstruction (%) was defined as neointimal volume divided by stent volume. Cross-sectional narrowing (CSN, %) was defined as neointimal area divided by stent area. No significant differences in vessel, lumen and stent volume at post-procedure were observed within stented segments between the 4- and 9-month follow-up groups. Although neointimal volume and % neointimal obstruction showed no significant difference between the 2 groups (% neointimal obstruction: 2.2 ± 2.5 vs 3.7 ± 4.0%, P=0.09), maximum CSN was significantly larger in the 9-month group. There were 7 cases of late incomplete stent apposition.. These IVUS results showed minimum growth of neointimal proliferation by the Resolute stent throughout the stented segment up to 9 months follow up. 

Topics: Aged; Coronary Vessels; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neointima; Polymers; Sirolimus; Time Factors; Ultrasonography, Interventional

Normalized optical density (NOD) measured by optical coherence tomography represents neointimal maturity after coronary stent implantation and is correlated with morphologic information provided by both light and electron microscopy. We aimed to test the hypothesis that even second generation drug-eluting stents (DESs) are problematic in terms of neointimal maturity. We implanted bare-metal stents (BMS: n = 14), everolimus-eluting stents (EESs: n = 15) or zotarolimus-eluting stents (ZESs: n = 12) at 41 sites in 32 patients with stable coronary artery disease. OCT was performed at up to 12 months of follow-up, and the average optical density of neointima covering struts was evaluated. NOD was calculated as the optical density of stent-strut covering tissue divided by the optical density of the struts. We also measured circulating CD34+ /CD133+ /CD45low cells, and serum levels of stromal cell-derived factor (SDF)-1, interleukin (IL)-8 and matrix metalloproteinase (MMP)-9 at baseline and follow-up. NOD was lower in the EES (0.70 ± 0.06) group than in the BMS (0.76 ± 0.07, P < 0.05) and ZES (0.76 ± 0.06, P < 0.05) groups. The mean neointimal area (R = 0.33, P < 0.05) and mean neointimal thickness (R = 0.37, P < 0.05) were correlated with NOD. Although NOD was not correlated with percent changes in circulating endothelial progenitor cells, and the levels of SDF-1 and IL-8, it was negatively correlated with the change in MMP-9 level (R = - 0.51, P < 0.01). Neointimal maturity might be lower at EES sites than BMS or ZES sites. This might lead to impaired neointimal tissue growth and matrix degradation. These results suggest a specific pathophysiology after DES implantation.

Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Chemokine CXCL12; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Endothelial Progenitor Cells; Everolimus; Female; Humans; Interleukin-8; Male; Matrix Metalloproteinase 9; Middle Aged; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Vascular Remodeling

Drug-eluting stents (DES) have evolved to using bioresorbable polymers as a method of drug delivery. The impact of bioresorbable polymer on long-term neointimal formation, inflammation, and healing has not been fully characterised. This study aimed to evaluate the biological effect of polymer resorption on vascular healing and inflammation.. A comparative DES study was performed in the familial hypercholesterolaemic swine model of coronary stenosis. Permanent polymer DES (zotarolimus-eluting [ZES] or everolimus-eluting [EES]) were compared to bioresorbable polymer everolimus-eluting stents (BP-EES) and BMS. Post implantation in 29 swine, stents were explanted and analysed up to 180 days. Area stenosis was reduced in all DES compared to BMS at 30 days. At 180 days, BP-EES had significantly lower area stenosis than EES or ZES. Severe inflammatory activity persisted in permanent polymer DES at 180 days compared to BP-EES or BMS. Qualitative para-strut inflammation areas (graded as none to severe) were elevated but similar in all groups at 30 days, peaked at 90 days in DES compared to BMS (p<0.05) and, at 180 days, were similar between BMS and BP-EES but were significantly greater in DES.. BP-EES resulted in a lower net long-term reduction in neointimal formation and inflammation compared to permanent polymer DES in an animal model. Further study of the long-term neointima formation deserves study in human clinical trials.

Topics: Absorbable Implants; Animals; Coronary Stenosis; Disease Models, Animal; Drug-Eluting Stents; Everolimus; Inflammation; Neointima; Percutaneous Coronary Intervention; Polymers; Sirolimus; Swine; Wound Healing

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

The aim of this study was to investigate whether the underlying plaque type affects the neointimal coverage after drug-eluting stent implantation.. A total of 1793 struts in 22 zotarolimus-eluting stents were assessed using optical coherence tomography imaging within 3 months of implantation. Neointimal coverage was evaluated within 5 mm from each stent edge on cross-sectional optical coherence tomography images at every 1-mm interval. The percentage of struts covered by neointima was compared among the normal segment group, the fibrous plaque group, and the lipid plaque group on the basis of the underlying plaque type.. The percentage of covered strut was significantly lower in the normal segment group than in the fibrous plaque group (35.9±30.2 vs. 57.1±31.0%, P<0.05) and the lipid plaque group (vs. 64.7±23.5%, P<0.01). The neointima was significantly thinner in the normal segment group than in the lipid plaque group (19.0±22.3 vs. 32.0±18.8 μm, P<0.01). The percentage of struts on the normal segment was significantly higher in cross-sections with a ratio of uncovered to total struts per section more than 0.3 than in cross-sections with a ratio up to 0.3 (32.4±31.7 vs. 19.5±33.8%, P<0.01).. Struts on the normal segment were less covered and had thinner neointima than struts on the lipid plaque at the stent edge within 3 months after zotarolimus-eluting stent implantation. Caution should be exercised when implanting longer drug-eluting stents to achieve uniform strut coverage in the early phase.

Topics: Aged; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Female; Fibrosis; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Plaque, Atherosclerotic; Prosthesis Design; Retrospective Studies; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

The aim of this study was to evaluate neointimal coverage in the very early phase after second-generation drug-eluting stent (DES) implantation using optical coherence tomography (OCT). Patients who underwent staged percutaneous coronary intervention within 30 days after DES implantation were enrolled. OCT was performed to observe DES previously implanted. The median time interval from implantation to OCT examination was 21.5 days. A total of 10,625 struts of 54 stents (52 everolimus-eluting stents and 2 zotarolimus-eluting stents) in 42 lesions were analyzed. Strut tissue coverage was observed in 71.1 ± 19.2 % of the struts, malapposed struts in 2.56 ± 3.37 %, strut tissue coverage at the side branch orifice in 10.6 ± 17.2 %, and struts with protrusion in 0.95 ± 3.46 %. Mean tissue thickness on the covered struts was 39.8 ± 14.2 µm. The percentage of stent coverage was significantly lower in the overlapping segments than in the non-overlapping segments (48.4 ± 17.5 % vs. 74.4 ± 20.2 %, P < 0.05). Most of the stent struts were covered by tissue within 30 days after second-generation DES implantation. However, the percentage of strut coverage was lower in the overlapping segments than in the non-overlapping segments, suggesting that very early interruption of dual antiplatelet therapy might result in increased risk of stent thrombosis, even in second-generation DES.

Topics: Aged; Cardiovascular Agents; Coronary Artery Disease; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Japan; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prospective Studies; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

Few studies have directly compared vascular responses to second-generation drug-eluting stents (DESs). We performed optical coherence tomography examinations in 56 consecutive patients with implanted single stent [19 cobalt-chromium everolimus-eluting stents (CoCr-EES), 22 platinum-chromium EES (PtCr-EES), and 15 resolute zotarolimus-eluting stents (R-ZES)] for de novo lesions, and who did not have restenosis at their 9-month follow-up. Neointimal thickness (NIT), stent apposition, and neointimal coverage were assessed in every strut. A neointimal unevenness score [(NUS), maximum NIT/average NIT in the same cross-section] was determined for every 1-mm cross-section (CS). A total of 8350 struts and 1159 CSs were analyzed. The CoCr- and PtCr-EES had significantly fewer malapposed struts compared to the R-ZES (CoCr-EES: 0.19 % vs. PtCr-EES: 0.19 % vs.. 0.61 %, p = 0.007). Furthermore, the PtCr-EES had a lower frequency of uncovered struts compared to the others (CoCr-EES: 2.0 % vs. PtCr-EES: 1.4 % vs.. 2.3 %, p = 0.047). The NUS correlated with the frequency of uncovered struts (p < 0.001, r = 0.54). The EESs demonstrated more homogenous neointimal growth, as shown in the NUS, compared to the R-ZES [CoCr-EES: 1.66 (1.38-1.97) vs. PtCr-EES: 1.67 (1.41-2.00) vs.. 1.94 (1.56-2.28), p < 0.001]. Our results demonstrate that unevenness neointimal growth may relate with strut coverage after second-generation DES implantation. The PtCr-EES had a high frequency of strut coverage with a homogeneous neointima, suggesting fewer risks for stent thrombosis.

Topics: Aged; Cardiovascular Agents; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Metals; Middle Aged; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Retrospective Studies; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

First-generation drug-eluting stents (DES) have reduced short-term stent failure as compared to bare-metal stents due to the inhibition of neointima hyperplasia, but instead increased the risk of very-late stent failure. Although better outcomes have been reported for second-generation DES than for first-generation DES, the difference in the angioscopic findings at 1-year follow-up has not been adequately elucidated among second-generation DES.. Consecutive 161 patients who received angioscopic examination at 1 year after implantation of second-generation DES, i.e. Nobori biolimus-eluting stents (Terumo, Tokyo, Japan) (N-BES, n=25), Xience everolimus-eluting stents (Abbot Vascular, Santa Clara, CA, USA; X-EES, n=95), or Resolute zotarolimus-eluting stents (Resolute Integrity; Medtronic, Minneapolis, MN, USA; R-ZES, n=41), in de novo native coronary lesions were analyzed.. Maximum neointima coverage grade (N-BES, 0.9±0.3; X-EES, 1.2±0.4; R-ZES, 1.5±0.5; p<0.001) was the highest in R-ZES and lowest in N-BES. Heterogeneity score was higher in R-ZES than in N-BES (N-BES, 0.8±0.4; X-EES, 0.9±0.4; R-ZES, 1.1±0.5; p=0.007). Maximum yellow color grade and prevalence of thrombus were not different. Multivariate analysis demonstrated that only stent type was associated with maximum neointima coverage grade; stent type and total stent length were associated with heterogeneity score; and stenting for acute coronary syndrome (ACS) and total stent length were associated with maximum yellow color grade.. Neointima coverage and heterogeneity were mainly determined by stent type even among second-generation DES, while yellow color was determined mainly by whether target lesion was of ACS.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Angioscopy; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neointima; Sirolimus; Thrombosis; Treatment Outcome

Very late stent thrombosis (VLST) is a serious complication after percutaneous coronary intervention. However, the best therapy for VLST with late-acquired incomplete stent apposition and incomplete neointimal coverage remains unknown. In these cases, neointimal coverage was nearly complete and no late-acquired malapposition was detected at 18 months after Endeavor zotarolimus-eluting stent (ZES) implantation for the treatment of VLST with late-acquired incomplete stent apposition after sirolimus-eluting stent implantation. We presented that Endeavor ZES implantation may become an attractive therapeutic strategy for the treatment of VLST with late-acquired incomplete stent apposition and incomplete neointimal coverage.

Topics: Aged; Angioplasty, Balloon; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Thrombosis; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Prosthesis Design; Sirolimus; Thrombectomy; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

Overall stent performance should be characterized by geometric luminal gain acquisition, neointimal coverage of the stent struts, and stabilization of the underlying inflammatory neoatheroma. The aim of this study was to compare the performance of zotarolimus-eluting stent (ZES), everolimus-eluting stent (EES) and bare metal stent (BMS) using optical coherence tomography (OCT) and coronary angioscopy. For 36 stented coronary lesions (BMS, 12 lesions; ZES, 11 lesions; EES, 13 lesions) in 27 patients, we calculated neointimal area and uncovered stent strut rate based on OCT findings at 10 months after stent placement. The grades of neointimal coverage and yellow color, both of which were classified from 0 to 3, were also assessed by coronary angioscopy. The plaque area of the ZES lesions was larger than that of the EES lesions (P < 0.05) but smaller than that of the BMS lesions (P < 0.05). The OCT-based uncovered rate of the ZES lesions was less than that of the EES lesions (P < 0.01), but similar to that of the BMS lesions. The stent coverage grade by angioscopy was higher in the ZES lesions than in the EES lesions (P < 0.05), but similar to the BMS lesions. The yellow grade was less in the ZES lesions than in the EES lesions (P < 0.01), but similar to the BMS lesions. ZES might be better than BMS in terms of neointimal thickening, and better than EES in terms of neointimal coverage as well as prevention of neoatheroma formation. ZES may have superior performance compared with EES.

Topics: Aged; Angioscopy; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Neointima; Sirolimus; Tomography, Optical Coherence

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

In-stent hyperplasia (ISH) may develop in regions of low endothelial shear stress (ESS), but the relationship between the magnitude of low ESS, the extent of ISH, and subsequent clinical events has not been investigated.. We assessed the association of poststent ESS with neointimal ISH and clinical outcomes in patients treated with percutaneous coronary interventions (PCI). Three-dimensional coronary reconstruction was performed in 374 post-PCI patients at baseline and 6 to 10 months follow-up as part of the PREDICTION Study. Each vessel was divided into 1.5-mm-long segments, and we calculated the local ESS within each stented segment at baseline. At follow-up, we assessed ISH and the occurrence of a clinically indicated repeat PCI for in-stent restenosis. In 246 total stents (54 overlapping), 100 (40.7%) were bare-metal stents (BMS), 104 (42.3%) sirolimus-eluting stents, and 42 (17.1%) paclitaxel-eluting stents. In BMS, low ESS post-PCI at baseline was independently associated with ISH (β=1.47 mm(2) per 1-Pa decrease; 95% CI, 0.38-2.56; P<0.01). ISH was minimal in drug-eluting stents. During follow-up, repeat PCI in BMS was performed in 21 stents (8.5%). There was no significant association between post-PCI ESS and in-stent restenosis requiring PCI.. Low ESS after BMS implantation is associated with subsequent ISH. ISH is strongly inhibited by drug-eluting stents. Post-PCI ESS is not associated with in-stent restenosis requiring repeat PCI. ESS is an important determinant of ISH in BMS, but ISH of large magnitude to require PCI for in-stent restenosis is likely attributed to factors other than ESS within the stent.

Topics: Aged; Coronary Restenosis; Drug-Eluting Stents; Early Diagnosis; Female; Follow-Up Studies; Hemodynamics; Humans; Hyperplasia; Immunosuppressive Agents; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Sirolimus; Stents; Stress, Mechanical; Treatment Outcome

This study evaluated the safety and efficacy of the RESOLUTE(TM)zotarolimus-eluting stent (R-ZES; Medtronic, Inc, Santa Rosa, CA, USA) in Japanese patients for the treatment of de novo native coronary lesions.. Both RESOLUTE Japan (R-Japan) and RESOLUTE Japan Small Vessel Study (R-Japan SVS) were prospective, multicenter, single-arm observational studies. R-Japan enrolled 100 patients (reference vessel diameter, 2.5-3.5 mm) and R-Japan SVS enrolled 65 patients (at least 1 lesion suitable for 2.25-mm stent) treated with R-ZES. In R-Japan, in-stent late lumen loss (LLL; the primary endpoint) at 8 months was 0.12 ± 0.22 mm and volume obstruction on intravascular ultrasound was 2.33 ± 3.51%. At 4 years, there were no cases of clinically driven target lesion revascularization (TLR); the target lesion failure (TLF; composite of cardiac death, target vessel myocardial infarction, and clinically driven TLR) was 5.6% (5/90). In R-Japan SVS, in-stent LLL at 9 months was 0.27 ± 0.33 mm, TLF (primary endpoint) was 4.6% (3/65), without incidence of TLR. At 3 years, TLF was 7.9% (5/63) and clinically driven TLR, 3.2% (2/63).. R-Japan and R-Japan SVS demonstrate substantial suppression of neointimal hyperplasia, low LLL, and excellent and sustained long-term clinical outcome with R-ZES in Japanese patients.

Topics: Combined Modality Therapy; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Heart Diseases; Humans; Incidence; Japan; Myocardial Infarction; Myocardial Revascularization; Neointima; Platelet Aggregation Inhibitors; Postoperative Complications; Prospective Studies; Risk Factors; Sirolimus; Treatment Outcome; Ultrasonography, Interventional

Topics: Absorbable Implants; Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Coronary Stenosis; Drug-Eluting Stents; Female; Humans; Middle Aged; Neointima; Percutaneous Coronary Intervention; Prosthesis Design; Prosthesis Failure; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

The most common causes of in-stent restenosis (ISR) are intimal hyperplasia and stent under expansion. The purpose of this study was to use intravascular ultrasound (IVUS) to compare the ISR mechanisms of bare metal stents (BMS), first-generation drug-eluting stents (DES), and second-generation DES. There were 298 ISR lesions including 52 BMS, 73 sirolimus-eluting stents, 52 paclitaxel-eluting stents, 16 zotarolimus-eluting stents, and 105 everolimus-eluting stent. Mean patient age was 66.6 ± 1.1 years, 74.2% were men, and 48.3% had diabetes mellitus. BMS restenosis presented later (70.0 ± 66.7 months) with more intimal hyperplasia compared with DES (BMS 58.6 ± 15.5%, first-generation DES 52.6 ± 20.9%, second-generation DES 48.2 ± 22.2%, p = 0.02). Although reference lumen areas were similar in BMS and first- and second-generation DES, restenotic DES were longer (BMS 21.8 ± 13.5 mm, first-generation DES 29.4 ± 16.1 mm, second-generation DES 32.1 ± 18.7 mm, p = 0.003), and stent areas were smaller (BMS 7.2 ± 2.4 mm(2), first-generation DES 6.1 ± 2.1 mm(2), second-generation DES 5.7 ± 2.0 mm(2), p <0.001). Stent fracture was seen only in DES (first-generation DES 7 [5.0%], second-generation DES 8 [7.4%], p = 0.13). In conclusion, restenotic first- and second-generation DES were characterized by less neointimal hyperplasia, smaller stent areas, longer stent lengths, and more stent fractures than restenotic BMS.

Topics: Aged; Coronary Restenosis; Drug-Eluting Stents; Everolimus; Female; Humans; Immunosuppressive Agents; Male; Metals; Middle Aged; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Prosthesis Design; Retrospective Studies; Risk Factors; Sirolimus; Stents; Time Factors; Treatment Outcome; Ultrasonography, Interventional

Several studies have reported re-endothelialization and endothelial function after drug-eluting stent (DES) implantation; however, the relationship between re-endothelialization and endothelial function after DES implantation has not been investigated yet.. A total of 14 patients underwent evaluation of re-endothelialization by optical coherence tomography (OCT) and endothelial function by incremental Ach infusion at 9 months after DES implantation (ZES: N = 7, PES: N = 7). The neointimal thickness (NIT) inside each strut, strut coverage, and malapposition at every 1 mm cross-section were evaluated by OCT and the endothelial function was estimated by measuring the coronary vaso-reactivity in response to acetylcholine (Ach) infusion into coronary arteries.. Zotarolims eluting stent (ZES), compared with paclitaxcel eluting stent (PES), showed more homogeneous neointimal coverage of stent struts and low rate of malapposition. Vasoconstriction in response to Ach in the peri-stent region was also less pronounced in ZES than PES. In particular, vasoconstriction was more often observed in cases with inhomogeneous neointimal coverage of stent struts in the PES group.. Our findings suggest that endothelial function seems to be better preserved with ZES than PES, and homogeneous neointimal coverage of stent struts seem to be associated with the preserved endothelial function.

Topics: Acetylcholine; Aged; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Endothelial Cells; Female; Humans; Infusions, Intra-Arterial; Male; Middle Aged; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Prosthesis Design; Re-Epithelialization; Retrospective Studies; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Vasoconstriction; Vasoconstrictor Agents

Neointimal proliferation of bifurcation lesions after implantation of drug-eluting stents (DES) has not been well evaluated. Thus, we compared neointimal proliferation of bifurcation lesions among four DES using optical coherence tomography (OCT).. 8-month follow-up OCT was performed in 68 bifurcation lesions treated by 15 sirolimus-eluting stents (SES) and 17 paclitaxel-eluting stents (PES) as first-generation DES, and by 17 zotarolimus-eluting stents (ZES) and 19 everolimus-eluting stents (EES) as second-generation DES. Cross-sectional images of the bifurcation lesion using OCT were analyzed every 450 µm. All images were divided into three areas: inner wall of the bifurcation (IB), outer wall of the bifurcation (OB), and ostium of the side branch (SB). We compared the incidence of uncovered struts (IUS) among three areas and the averaged neointimal thickness (NIH) between IB and OB in each stent and also compared these OCT parameters among all DES.. There were no significant differences of IUS between IB and OB in second-generation DES, while in first-generation DES, IUS of IB and OB showed significant differences. The IUS of SES in both areas was significantly higher than in the other DES (all P < 0.001). PES had a significantly higher IUS in SB than the others (all P < 0.001). NIH of OB was significantly higher than that of IB in PES, ZES, and EES, but in SES the NIH was similar in the two areas.. OCT revealed different neointimal growth patterns among SES, PES, ZES, and EES in bifurcation lesions.

Topics: Aged; Angioplasty, Balloon, Coronary; Coronary Stenosis; Cross-Sectional Studies; Drug-Eluting Stents; Everolimus; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neointima; Paclitaxel; Prosthesis Failure; Retrospective Studies; Risk Assessment; Severity of Illness Index; Sirolimus; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

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

Arterial repair in the early phase following implantation of a zotarolimus-eluting stent (ZES) remains unknown.. Following implantation of 49 Endeavor ZES in 33 patients, follow-up angioscopy was performed in 13 patients (26 ZES) in the early phase (EP; 123±24 days) and in 20 patients (23 ZES) in the middle phase (MP; 247±17 days). Neointimal coverage (NIC) was graded as follows: grade 0, stent struts exposed; grade 1, struts bulging into the lumen, although covered; grade 2, struts were embedded by the neointima but were seen translucently; grade 3, struts fully embedded and invisible. NIC was defined as heterogeneous for NIC grade variation≥1. The presence of thrombus and yellow plaque was also investigated. Although NIC heterogeneity tended to be more frequent in EP than in MP (50% vs. 22%, P=0.070), and yellow plaque significantly more frequent (58% vs. 13%, P=0.0025), the majority of stents were dominant NIC grade 3 at both follow-up periods (73% in EP vs. 78% in MP, P=0.75). There was no significant difference in thrombus (23% in EP vs. 4% in MP, P=0.10) between the follow-ups.. Sufficient arterial repair may have occurred by 4 months after ZES implantation. 

Topics: Aged; Aged, 80 and over; Angioscopy; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

The presence of uncovered struts overlying side branch is considered to be a potential risk of stent thrombosis. The accuracy in detection of neointimal strut coverage at branch point by optical coherence tomography (OCT) has not been validated in comparison with histology.. A total of 5 stents (3 drug-eluting stents and 2 bare-metal stents) were implanted in the bifurcation segment of normal coronary arteries in 4 domestic swine (weight, 25-40 kg). The animals underwent follow-up OCT at 30 days after stent implantation and were then sacrificed for histologic evaluation. The neointimal coverage of the non-apposed struts over the side branch was assessed by light microscopy. Every millimeter of the stent was specified by the OCT frame rate, and comparisons between OCT and pathologic findings were performed through precise histological-OCT frame matching.. OCT images at the side branch corresponded well with histological cross-sections. The tissues covering struts as assessed by OCT contained smooth muscle cells with proteoglycan-collagen matrix, but platelets are attached above the neointima in one of them on histologic examination, suggesting that most of the struts were well healed, with normal neointimal coverage.. This study demonstrated the accuracy of OCT for the detection of neointimal coverage of non-apposed struts over the side branch.

Topics: Animals; Coronary Vessels; Drug-Eluting Stents; Incidence; Metals; Models, Animal; Muscle, Smooth, Vascular; Neointima; Risk Factors; Sirolimus; Stents; Sus scrofa; Tomography, Optical Coherence

To obtain imaging evidence by 2-week optical coherence tomography (OCT) on the completion of neointimal coverage (NIC; the percentage of stent strut coverage and thickness of the formed neointima) completion after implantation of the Endeavor zotarolimus-eluting stent (E-ZES).. Despite the fact that NIC is a cardinal process in the pathomechanism of late stent thrombosis, little imaging information is available on morphological changes thereof on a short-time interval basis.. 27 Japanese patients with stable angina pectoris and de novo native coronary artery lesions were enrolled, and 27 lesions (30 implantations) were examined. OCT was performed at weeks 2, 4, 6, 8, and 10 after E-ZES implantation. NIC was examined using cross-sectional OCT images obtained at the 1.0-mm intervals.. In total, 621 cross-sectional OCT images, which depicted 7,747 stent struts, were analyzed. The mean percentages of stent strut coverage at weeks 2, 4, 6, 8, and 10 after E-ZES implantation were 12.3, 70.4, 67.9, 86.0, and 99.2%, respectively; a marked increase was found between weeks 2 and 4. The mean thicknesses of the formed neointima were 40.2, 52.1, 48.1, 86.5, and 146.2 μm at respective weeks, with the high-signal and thick neointima (146 µm) at week 10. An intracoronary thrombus was detected in only one stent at week 4.. The full circumferential coverage of the vessel wall by the high-signal neointima was found at as early as week 10 after E-ZES implantation, imparting a surrogate index for vascular healing by NIC.

Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Coronary Artery Disease; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Japan; Male; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Wound Healing

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

Previous optical coherence tomography (OCT) studies in patients with drug-eluting stents (DESs)-related very late stent thrombosis (VLST) were scarce. Therefore, we investigated OCT findings of VLST after implantation of DESs. Using OCT, we analyzed the status of stent struts and neointimal characteristics in 18 patients who developed VLST after DES implantation. These results were compared to those in 57 patients with neointimal hyperplasia causing >40% diameter stenosis. Lipid-laden neointima was defined as a region with marked signal attenuation and a diffuse border. Four (22.2%) of 18 patients with VLST had ruptured and lipid-laden neointima inside DESs without uncovered or malapposed stent struts. In the remaining 14 patients who developed VLST without neointimal rupture, uncovered and malapposed struts were observed in nine and seven patients, respectively, and lipid-laden neointima in four patients. Lipid-laden neointima was more frequently observed in four patients with neointimal rupture than in 14 patients without neointimal rupture (100% vs. 28.6%, respectively, P = 0.023). Of 57 patients with neointimal hyperplasia, eight (14.0%) had lipid-laden neointima. Time to OCT study after DES implantation was significantly longer in the eight patients with lipid-laden neointima than in 49 patients without lipid-laden neointima (45.5 ± 17.7 months vs. 11.7 ± 7.2 months, respectively, P < 0.001). Lipid-laden neointima was detected in some patients with neointimal hyperplasia > 1 year after DES implantation. In addition to uncovered or malapposed struts, rupture of lipid-laden neointima inside DESs was identified in some patients with DES-related VLST.

Topics: Adult; Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Hyperplasia; Lipid Metabolism; Male; Middle Aged; Neointima; Paclitaxel; Predictive Value of Tests; Prosthesis Design; Republic of Korea; Risk Assessment; Risk Factors; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

The Resolute zotarolimus-eluting stent (ZES-R) has a thinner stent strut with biocompatible polymer than first generation drug-eluting stents. However, minimal optical coherence tomography (OCT) data exists about vascular responses after ZES-R implantation. This study investigated OCT findings in ZES-R implantation and compared them to those in sirolimus-eluting stent (SES) implantation. A total of 123 lesions (43 ZES-R and 80 SES) in 111 patients were evaluated with OCT at 9 months after stent implantation. Strut apposition, neointimal hyperplasia (NIH) thickness, and stent coverage on each stent strut were evaluated. Mean NIH thickness was significantly greater in ZES-R-treated lesions than in SES-treated lesions (166 ± 73 μm vs. 96 ± 63 μm, respectively, P < 0.001). The percentage of uncovered strut was significantly lower in ZES-R-treated lesions than in SES-treated lesions (4.4 ± 4.8% vs. 10.3 ± 13.2%, respectively, P = 0.05). The percentage of malapposed struts was also significantly lower in ZES-R-treated than in SES-treated lesions (0.1 ± 0.4% vs. 1.5 ± 4.2%, respectively, P = 0.002). Intracoronary thrombus was less frequently detected in ZES-R-treated lesions (4.7% vs. 30.0%, respectively, P = 0.001). ZES-R showed a lower incidence of uncovered or malapposed stent struts and intracoronary thrombus than SES at 9-month follow-up OCT examination. Compared with SES, ZES-R may elicit more favorable vascular responses at the expense of an increased neointimal proliferation.

Topics: Aged; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Linear Models; Male; Middle Aged; Multivariate Analysis; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prosthesis Design; Registries; Retrospective Studies; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

Topics: Cardiovascular Agents; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Female; Humans; Male; Neointima; Percutaneous Coronary Intervention; Sirolimus; Tomography, Optical Coherence

The differences in the vascular response to stent implantation or in the incidence of late acquired stent malapposition among different types of drug-eluting stents are not well known in patients with acute myocardial infarction (MI).. The pattern of vascular remodeling and degree of neointimal proliferation were different depending on the different types of drug-eluting stents.. This study used intravascular ultrasound (IVUS) to investigate vascular remodeling in patients treated with implantation of sirolimus-eluting stents (SESs) vs zotarolimus-eluting stents (ZESs) following acute MI. The study population consisted of 100 patients with acute MI who were treated either with SES (n = 41) or ZES (n = 59) and underwent both poststenting and 9-month follow-up IVUS examination. Serial vascular changes surrounding stented segments were compared between SES- and ZES-treated lesions.. Percentage of neointimal volume obstruction at follow-up was significantly smaller in SES-treated compared to ZES-treated lesions (2.8 ± 7.1% vs 18.1 ± 15.7%, respectively; P < 0.001). However, positive vascular remodeling, which was defined as greater than 10% increase in external elastic membrane volume index (31.7% vs 10.2%, respectively, P = 0.007), and late acquired stent malapposition (12.0% vs 0%, respectively, P = 0.006 ) occurred more frequently in SES-treated than in ZES-treated lesions.. The pattern of vascular remodeling, including positive remodeling, late acquired stent malapposition, and degree of neointimal proliferation might be different depending on the different types of drug-eluting stents in patients with acute MI.

Topics: Angioplasty, Balloon, Coronary; Coronary Angiography; Coronary Vessels; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Male; Myocardial Infarction; Neointima; Sirolimus; Treatment Outcome; Ultrasonography, Interventional

Non stent based delivery of antiproliferative agents using drug coated balloon catheters may offer additional flexibility and efficacy in a broad range of applications. The lipophilic antiproliferative drug zotarolimus makes it a potential candidate for balloon delivery. The aim of the present study was to evaluate the safety and efficacy of a prototype zotarolimus coated balloon (ZCB) catheter in comparison to a zotarolimus eluting stent (ZES) in the porcine coronary overstretch model.. Eighty-four stents (diameters 3.0 and 3.5 mm; length 15 mm) were implanted in LAD and Cx of 42 domestic pigs: control (TriMaxx, Abbott, polymer coated stent without drug, implanted with uncoated PCI catheter, n = 56); ZES (ZoMaxx, Abbott, stent coated with zotarolimus in polymer, implanted with uncoated PCI catheter, n = 14); ZCB (TriMaxx, Abbott, polymer coated stent without drug, implanted with zotarolimus coated PCI catheter, n = 14). Drug content of the vessel wall (n = 9) was measured about 10-30 min post intervention with ZCB in additional pigs.. Immediately after ZCB treatment 101 ± 31 μg of zotarolimus was detected in the coronary arteries. After 28 days ZES led to a reduction of neointimal area from 4.32 ± 1.45 to 3.32 ± 1.11 mm2 (P = 0.019 vs. control). The effect of neointimal inhibition was more pronounced with the novel ZCB (2.79 ± 1.43 mm², P = 0.001 vs. control). Inflammation score was significantly reduced in vessels treated with the ZCB (0.75 ± 0.86 compared to control (1.45 ± 0.94, P = 0.013) and ZES (1.65 ± 0.90, P = 0.012).. Zotarolimus coated balloons and stents were found to effectively reduce neointimal proliferation in the porcine coronary model. Inflammation scores were significantly reduced after treatment with the coated balloon. Zotarolimus balloon coating might be a novel option in preventing and treating restenosis.

Topics: Angioplasty, Balloon, Coronary; Animals; Coronary Restenosis; Coronary Vessels; Disease Models, Animal; Drug-Eluting Stents; Hyperplasia; Neointima; Sirolimus; Swine

We aimed to assess the influence of different sirolimus analogues released from a uniform stent platform on re-endothelialisation and vascular healing responses.. Bare metal stents (BMS) were coated with a fluoropolymer containing everolimus (EES), sirolimus (SES) or zotarolimus (ZES) to generate drug-eluting stents (DES) with identical stent backbones, drug loads and release kinetics. DES constructs and control BMS were implanted into the iliac arteries of rabbits and were analysed at 14 days by scanning electron microscopy (SEM) and confocal microscopy for en face evaluation of endothelialisation (n=6 for each stent), or at 28 days to determine histomorphometric characteristics (n=11 for each stent). SEM analysis revealed low degrees of strut re-endothelialisation within the DES without differences among groups, while the BMS control showed almost complete endothelialisation. Percent stenosis was significantly reduced in all DES compared to BMS. Strut-based fibrin analysis revealed significantly greater deposition in the DES compared to BMS, with EES showing maximum fibrin deposition among the DES groups.. Sirolimus and its derivatives have similar effects on endothelial regrowth and neointimal thickening. The observation of greatest fibrin deposition in the experimental EES group indicates that everolimus may affect vascular healing differently.

Topics: Angioplasty, Balloon; Animals; Biomarkers; Cardiovascular Agents; Drug-Eluting Stents; Endothelial Cells; Everolimus; Fibrin; Iliac Artery; Immunohistochemistry; Male; Metals; Microscopy, Confocal; Microscopy, Electron, Scanning; Models, Animal; Neointima; Platelet Endothelial Cell Adhesion Molecule-1; Prosthesis Design; Rabbits; Sirolimus; Time Factors; Wound Healing

Serial changes in strut coverage of drug-eluting stents (DESs), which are placed across side-branch vessels, remain unclear.. The changes in strut coverage of DESs crossing side-branch vessels (size ≥2.0 mm) were serially evaluated by optical coherence tomography (OCT) in 30 patients at 9 months and 2 years after the index DES implantation. DESs were paclitaxel-eluting stents (PESs), sirolimus-eluting stents (SESs), and zotarolimus-eluting stents (ZESs), each in 10 patients. Measured neointimal hyperplasia (NIH) thickness of 0 μm on OCT was defined as an uncovered strut.. The percentage of uncovered side-branch struts significantly decreased from 55.7 ± 39.9% to 36.6 ± 32.0% (P<.0001) on serial follow-up: PES, 93.4 ± 10.5% to 67.6 ± 24.2%, P=.018; SES, 47.5 ± 34.4% to 29.6 ± 24.1%, P=.036; and ZES, 26.2 ± 34.8% to 12.4 ± 19.0%, P=.028. Among covered side-branch struts, the overall percentage of struts with NIH thickness more than 30 μm significantly increased from 36.3 ± 37.4% to 51.0 ± 36.0% (P<.0001). However, compared to other DES types, a significant increase in relatively thin NIH (0 to 30 μm) was observed in PESs (1.6 ± 3.4% to 17.4 ± 16.0%; P=.018).. Serial follow-up OCT examination showed a significant decrease in the percentage of uncovered side-branch struts, and the coverage pattern differed with DES type.

Topics: Aged; Coronary Restenosis; Coronary Vessels; Drug-Eluting Stents; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Retrospective Studies; Sirolimus; Time Factors; Tomography, Optical Coherence

The study evaluated serial quantitative and qualitative changes in vascular responses to drug-eluting stents (DES) using optical coherence tomography (OCT).. Serial changes in stent strut coverage and neointima characteristics in DES-treated lesions have not been sufficiently investigated using OCT.. Serial OCT was performed in 72 patients with 76 DES-treated lesions at 9 months and 2 years after DES implantation (sirolimus-eluting stent, n = 23; paclitaxel-eluting stent, n = 20; zotarolimus-eluting stent, n = 25; everolimus-eluting stent, n = 8). Serial changes in quantitative parameters (neointimal thickness, stent strut coverage, and apposition at each strut) and qualitative characteristics of the neointima were evaluated.. Mean neointimal thickness significantly increased from 164 μm to 214 μm between 9 months and 2 years (p < 0.001), and the percentage of uncovered stent struts significantly decreased (from 4.4% to 2.3%, p < 0.001). Completely covered lesions were more frequently observed at 2 years (44.7% vs. 59.2%, p = 0.07). However, the percentage of malapposed struts (0.6% vs. 0.9%, p = 0.24) and incidence of intracoronary thrombi (10.5% vs. 9.2%, p > 0.99) were similar. On qualitative evaluation of neointimal morphology, lipid-laden neointima (27.6% vs. 14.5%, p = 0.009) and thin-cap neoatheroma (13.2% vs. 3.9%, p = 0.07) were more frequently detected at 2-year follow-up compared with 9 months. In matched cross-sectional evaluation, the change of neointimal morphology from homogeneous to heterogeneous or lipid-laden pattern was observed in 23 (30.3%) of 76 lesions. There was a significant increase in percent neointimal hyperplasia cross-sectional area in those lesions.. This OCT study suggested that neointimal coverage improved from 9 months to 2 years without significant changes in the incidence of malapposed struts and intracoronary thrombus. Additionally, in-stent neoatherosclerosis including transformation to lipid-laden neointima might progress during extended follow-up periods after DES implantation.

Topics: Aged; Cardiovascular Agents; Coronary Thrombosis; Coronary Vessels; Drug-Eluting Stents; Everolimus; Female; Humans; Male; Middle Aged; Neointima; Paclitaxel; Percutaneous Coronary Intervention; Predictive Value of Tests; Registries; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

Zotarolimus-eluting stents (ZES) have a higher rate of neointimal coverage than the first-generation drug-eluting stents on optical coherence tomography (OCT).. To determine whether neointimal coverage of stent struts detected by OCT can be used as a surrogate for endothelial function after ZES implantation.. Cross-sectional observational study.. Three months after ZES implantation.. OCT was performed in 20 patients with a ZES at 3 months after stent implantation to evaluate strut coverage. Endothelium-dependent coronary vasomotion was estimated by infusing incremental doses of acetylcholine into the coronary ostium. The vascular response was measured in the 10 mm segments proximal and distal to the stent.. Of 20 ZES, 15 (75%) were covered completely with neointima, but the remaining 5 ZES had exposed struts. The high-dose acetylcholine infusion produced significant vasoconstriction in the proximal (-9.8±10.1%) and the distal stent segment (-29.7±22.7%). However, the degree of vasoconstriction to acetylcholine varied between individuals (from -0.6% to -77%). Although no relationship was observed between coronary vasomotor response (percentage change in diameter after acetylcholine administration) and average neointimal thickness, the number of cross-sections with uncovered struts showed an inverse correlation with coronary vasomotor response in proximal and distal stent segments (r=-0.57, p=0.007 and r=-0.83, p<0.001, respectively).. The existence of exposed struts was associated with abnormal vasoconstriction to acetylcholine at 3 months after ZES implantation. The findings suggest that complete neointimal coverage of stent struts assessed by OCT could be used as a surrogate for vasomotion impairment at 3 months after ZES implantation.

Topics: Acetylcholine; Aged; Aged, 80 and over; Angina Pectoris; Coronary Vessels; Drug-Eluting Stents; Endothelium, Vascular; Female; Humans; Immunosuppressive Agents; Male; Neointima; Prospective Studies; Sirolimus; Tomography, Optical Coherence; Vasoconstrictor Agents; Vasodilator Agents; Vasomotor System; Wound Healing

Topics: Coronary Artery Disease; Diabetes Complications; Drug-Eluting Stents; Female; Humans; Male; Neointima; Radiography; Sirolimus; Ultrasonography

Drug-coated balloons are rapidly emerging as a therapeutic alternative for the interventional treatment of peripheral vascular disease. The purpose of this study was to test the hypothesis that an angioplasty balloon coated with the mTOR inhibitor zotarolimus (ZCB) would inhibit neointimal hyperplasia in a novel injury-based superficial femoral artery model in the familial hypercholesterolemic swine.. A total of 44 familial hypercholesterolemic swine were included (12 designated to study tissue pharmacokinetics and 32 to study safety and efficacy). Fogarty balloon denudation was performed in all superficial femoral artery segments, followed by balloon angioplasty. In the pharmacokinetic study, a total of 24 ZCBs (300 μg/cm(2)) were used. Zotarolimus was detected in arterial tissue at 5 minutes (162 ng/mg of tissue), 24 hours (5.9 ng/mg of tissue), and 28 days (0.007 ng/mg of tissue) after ZCB inflation. In the safety and efficacy study, superficial femoral artery segments were randomized to either high-dose (600 μg/cm(2), n=16), low-dose (300 μg/cm(2), n=16), or paired uncoated balloons (high-dose ZCB control, n=16; low-dose ZCB control, n=16). At 28 days, the percentage of angiographic stenosis was similar among all tested groups. Histological analysis demonstrated a reduction in neointimal formation in both ZCB groups compared with controls (high-dose ZCB 44% reduction, P=0.007; low-dose ZCB 22% reduction, P=0.08). There was no evidence of delayed arterial healing or vascular toxicity in any of the ZCB groups.. The single delivery of zotarolimus via coated balloon is feasible, and therapeutic levels are maintained up to 28 days. The ZCB technology appears to be effective in the reduction of neointimal proliferation in the superficial femoral artery of the familial hypercholesterolemic swine.

Topics: Angioplasty, Balloon; Animals; Catheterization; Clinical Protocols; Femoral Artery; Humans; Hyperlipoproteinemia Type II; Infusion Pumps, Implantable; Models, Animal; Neointima; Postoperative Complications; Radiography; Sirolimus; Swine; TOR Serine-Threonine Kinases