Serial Intravascular Ultrasound Analysis of Peri-Stent Remodeling and Proximal and Distal Edge Effects After Sirolimus-Eluting or Paclitaxel-Eluting Stent Implantation in Patients With Diabetes Mellitus

doi:10.1016/j.amjcard.2008.12.035

The American Journal of Cardiology

Volume 103, Issue 8, 15 April 2009, Pages 1083-1088

https://doi.org/10.1016/j.amjcard.2008.12.035 Get rights and content

Patients with diabetes have an increased risk of in-stent restenosis after coronary stent implantation. Serial intravascular ultrasound was used to study chronic arterial responses and edge effects after implantation of Cypher (Cordis, Johnson & Johnson, Miami Lakes, Florida) or Taxus (Boston Scientific, Maple Grove, Minnesota) stents in diabetic patients. Seventy-four diabetic patients were randomly assigned to Cypher or Taxus stent implantation. Intravascular ultrasound of 5-mm long segments immediately proximal and distal to the stent was performed after the procedure and at the 8-month follow-up. The increase in peri-stent external elastic membrane (EEM) volume was more pronounced in the Taxus group (292.4 ± 132.6 to 309.5 ± 146.8 mm³) than in the Cypher group (274.4 ± 137.2 to 275.4 ± 140.1 mm³; p = 0.005). Peri-stent plaque volume increased in the Taxus group (152.5 ± 73.7 to 166.1 ± 85.1 mm³), but was unchanged in the Cypher group (153.5 ± 75.5 to 151.5 ± 75.8 mm³; p = 0.002). In proximal and distal reference segments, mean lumen area decreased within the entire 5-mm edge segment (proximal and distal) because of plaque progression (distal, 5.5 ± 3.6 to 5.8 ± 3.7 mm²; p = 0.097; proximal, 8.1 ± 2.7 to 8.7 ± 2.9 mm²; p = 0.006) without remodeling (change in EEM) in the Taxus group. Conversely, there were no significant changes in reference-segment EEM or plaque areas in the Cypher group. In conclusion, in diabetic patients, Taxus stent implantation was associated with increased (1) peri-stent EEM volume and peri-stent plaque, and (2) stent edge plaque progression accompanied by lumen reduction without remodeling. These findings were not seen in Cypher stents.

Section snippets

Methods

The DiabeDES trial⁸ was a nonblinded, randomized, Danish, multicenter IVUS study. Patients were eligible for inclusion if they had diabetes mellitus and angiographically significant coronary stenoses in native coronary arteries (vessel diameter 2.25 to 4.0 mm). This was a substudy of The Danish Organization on Randomized Trials With Clinical Outcome (SORT OUT) II trial¹⁴ (Clinicaltrials.gov Identifier NCT00388934). All patients provided written informed consent, and the local institutional

Results

Of 130 patients enrolled in the DiabeDES trial,⁸ 74 had paired (after the procedure and follow-up) IVUS analyses (40 Cypher stents and 34 Taxus stents). The 2 groups were well balanced with respect to clinical and lesion characteristics (Table 1).

IVUS volumetric measurements for patients with complete post–stent implantation and 8-month follow-up studies are listed in Table 2. Postimplantation EEM, stent, and peri-stent plaque (EEM minus stent) volumes were similar in the Cypher and Taxus

Discussion

In the present study, vascular responses and intimal hyperplasia after coronary artery stent placement differed between Cypher and Taxus stents. Diabetic patients treated with Taxus stents had more intimal hyperplasia compared with diabetic patients treated with Cypher stents. Increases in peri-stent EEM volume and peri-stent plaque volume were seen in only diabetic patients treated with Taxus stents. In diabetic patients, Taxus stents were also associated with increased stent edge plaque

References (30)

A. Abizaid et al.
The influence of diabetes mellitus on acute and late clinical outcomes following coronary stent implantation
J Am Coll Cardiol
(1998)
G.S. Mintz et al.
American College of Cardiology Clinical Expert Consensus Document on Standards for Acquisition, Measurement and Reporting of Intravascular Ultrasound Studies (IVUS)A report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents
J Am Coll Cardiol
(2001)
G.S. Mintz et al.
Intravascular ultrasound in the drug-eluting stent era
J Am Coll Cardiol
(2006)
J.B. Hermiller et al.
Outcomes with the polymer-based paclitaxel-eluting TAXUS stent in patients with diabetes mellitus: the TAXUS-IV trial
J Am Coll Cardiol
(2005)
J. Aoki et al.
Chronic arterial responses to overlapping paclitaxel-eluting stents
J Am Coll Cardiol Interv
(2008)
N.J. Weissman et al.
Extent and distribution of in-stent intimal hyperplasia and edge effect in a non-radiation stent population
Am J Cardiol
(2001)
N.J. Weissman et al.
Polymer-based paclitaxel-eluting stents reduce in-stent neointimal tissue proliferation: a serial volumetric intravascular ultrasound analysis from the TAXUS-IV trial
J Am Coll Cardiol
(2005)
J. Ako et al.
Late incomplete stent apposition after sirolimus-eluting stent implantation: a serial intravascular ultrasound analysis
J Am Coll Cardiol
(2005)
P. Jimenez-Quevedo et al.
Vascular effects of sirolimus-eluting versus bare-metal stents in diabetic patients: three-dimensional ultrasound results of the Diabetes and Sirolimus-Eluting Stent (DIABETES) Trial
J Am Coll Cardiol
(2006)
A.S. Petronio et al.
Randomized comparison of sirolimus and paclitaxel drug-eluting stents for long lesions in the left anterior descending artery: an intravascular ultrasound study
J Am Coll Cardiol
(2007)

R. Kornowski et al.

Increased restenosis in diabetes mellitus after coronary interventions is due to exaggerated intimal hyperplasiaA serial intravascular ultrasound study

Circulation

(1997)

A. Dibra et al.

Paclitaxel-eluting or sirolimus-eluting stents to prevent restenosis in diabetic patients

N Engl J Med

(2005)

M. Sabate et al.

Randomized comparison of sirolimus-eluting stent versus standard stent for percutaneous coronary revascularization in diabetic patients: the Diabetes and Sirolimus-Eluting Stent (DIABETES) Trial

Circulation

(2005)

L.O. Jensen et al.

Neointimal hyperplasia after sirolimus-eluting and paclitaxel-eluting stent implantation in diabetic patients: the Randomized Diabetes and Drug-Eluting Stent (DiabeDES) Intravascular Ultrasound Trial

Eur Heart J

(2008)

K. Tanabe et al.

Chronic arterial responses to polymer-controlled paclitaxel-eluting stents: comparison with bare metal stents by serial intravascular ultrasound analyses: data from the randomized TAXUS-II trial

Circulation

(2004)

Cited by (14)

A randomized study to compare bioactive titanium stents and Everolimus-eluting stents in diabetic patients (TITANIC XV): 1-year results
2014, Revista Espanola de Cardiologia
Hasta un 25% de los pacientes sometidos a intervencionismo coronario percutáneo presentan alguna limitación para la utilización de los stents farmacoactivos. Nuestro objetivo es evaluar si el stent bioactivo de titanio y óxido nítrico podía ser una buena alternativa al stent de everolimus para pacientes diabéticos.
Se aleatorizó a 173 pacientes diabéticos con lesiones de riesgo de reestenosis intermedio (criterios de exclusión: diámetro < 2,5 mm o longitud > 28 mm en vasos < 3 mm, oclusión crónica): 83 pacientes en el grupo con titanio y 90 en el grupo con everolimus.
Las variables basales estaban bien equilibradas, el 28,3% eran insulinodependientes. Al año, las incidencias de eventos adversos cardiacos mayores (muerte, infarto de miocardio no fatal, ictus o nueva revascularización del vaso tratado) eran significativamente más frecuente en el grupo con titanio que en el grupo con everolimus (total, el 14,5 frente al 4,4%; p = 0,02; subgrupo no insulinodependiente, el 9,7 frente al 3,2%; p = 0,14; insulinodependiente, el 28,6 frente al 7,1%; p = 0,04) y de muerte, infarto de miocardio no fatal, ictus o cualquier revascularización, del 16,9% en el grupo con titanio y el 7,8% en el grupo con everolimus (p = 0,06). La revascularización de la lesión diana se produjo en el 8,4 frente al 3,3% (p = 0,15), y la del vaso tratado, el 13,3 frente al 3,3% (p = 0,01). El seguimiento angiográfico a 9 meses mostró una pérdida luminal tardía significativamente menor en el grupo con everolimus (en el segmento, 0,52 ± 0,58 frente a –0,05 ± 0,32 mm; en el stent, 0,76 ± 0,54 frente a 0,13 ± 0,31 mm; p < 0,0001).
El stent de everolimus fue superior al titanio en pacientes diabéticos incluso con lesiones de riesgo de eventos clínicos y angiográficos intermedio.
Up to 25% of patients who undergo a percutaneous coronary intervention show some limitation in the use of drug-eluting stents. The aim of this study was to evaluate if titanium-nitride-oxide–coated stents could be a good alternative to everolimus-eluting stents in diabetic patients.
A total of 173 diabetic patients with lesions at moderate risk of restenosis (exclusion criteria: diameter < 2.5 mm or length > 28 mm in vessels < 3 mm, chronic occlusion) were randomized to a titanium group (83 patients) or an everolimus group (90 patients).
Baseline characteristics were well balanced; 28.3% of patients were insulin dependent. At 1 year, the incidence of major adverse cardiac events (death, nonfatal myocardial infarction, stroke, or repeat target vessel revascularization) was significantly higher in the titanium group than in the everolimus group (total, 14.5% vs 4.4%; P = .02; noninsulin-dependent subgroup, 9.7% vs 3.2%; P = .14; insulin-dependent subgroup, 28.6% vs 7.1%; P = .04). The incidence of death, nonfatal myocardial infarction, stroke, or any revascularization was 16.9% in the titanium group and 7.8% in the everolimus group (P = .06). Target lesion and vessel revascularizations occurred in 8.4% compared with 3.3% (P = .15) and in 13.3% compared with 3.3% (P = .01) in the titanium and everolimus groups, respectively. Angiographic follow-up at 9 months showed significantly less late lumen loss in the everolimus group (in-segment, 0.52 [standard deviation, 0.58) mm vs –0.05 [0.32] mm; in-stent, 0.76 [0.54] mm vs 0.13 [0.31] mm; P < .0001).
The everolimus-eluting stent is superior to the titanium stent for clinical and angiographic end points in diabetic patients with lesions at moderate risk of restenosis.
Full English text available from: www.revespcardiol.org/en
Scaffold and edge vascular response following implantation of everolimus-eluting bioresorbable vascular scaffold: A 3-year serial optical coherence tomography study
2014, JACC: Cardiovascular Interventions
Citation Excerpt :
Trials with the Endeavor stent (Medtronic, Minneapolis, Minnesota) demonstrated a reduction in the luminal area at both the proximal and distal edges, mainly due to negative remodeling, plaque growth, and rapid elution of zotarolimus (24,25). However, serial IVUS examination in sirolimus- and everolimus-eluting stents revealed an enlargement of the luminal area at the distal edge (26–28). Our results are in agreement with those of previous reports on metal everolimus-eluting stents (28), with a significant increase in the distal-edge luminal area and a nonsignificant decrease in the proximal edge at 6-month follow-up.
This study sought to investigate the in-scaffold vascular response (SVR) and edge vascular response (EVR) after implantation of an everolimus-eluting bioresorbable scaffold (BRS) using serial optical coherence tomography (OCT) imaging.
Although studies using intravascular ultrasound have evaluated the EVR in metal stents and BRSs, there is a lack of OCT-based SVR and EVR assessment after BRS implantation.
In the ABSORB Cohort B (ABSORB Clinical Investigation, Cohort B) study, 23 patients (23 lesions) in Cohort B1 and 17 patients (18 lesions) in Cohort B2 underwent truly serial OCT examinations at 3 different time points (Cohort B1: post-procedure, 6 months, and 2 years; B2: post-procedure, 1 year, and 3 years) after implantation of an 18-mm scaffold. A frame-by-frame OCT analysis was performed at the 5-mm proximal, 5-mm distal edge, and 2-mm in-scaffold margins, whereas the middle 14-mm in-scaffold segment was analyzed at 1-mm intervals.
The in-scaffold mean luminal area significantly decreased from baseline to 6 months or 1 year (7.22 ± 1.24 mm² vs. 6.05 ± 1.38 mm² and 7.64 ± 1.19 mm² vs. 5.72 ± 0.89 mm², respectively; both p < 0.01), but remained unchanged from then onward. In Cohort B1, a significant increase in mean luminal area of the distal edge was observed (5.42 ± 1.81 mm² vs. 5.58 ± 1.53 mm²; p < 0.01), whereas the mean luminal area of the proximal edge remained unchanged at 6 months. In Cohort B2, the mean luminal areas of the proximal and distal edges were significantly smaller than post-procedure measurements at 3 years. The mean luminal area loss at both edges was significantly less than the mean luminal area loss of the in-scaffold segment at both 6-month and 2-year follow-up in Cohort B1 or at 1 year and 3 years in Cohort B2.
This OCT-based serial EVR and SVR evaluation of the Absorb Bioresorbable Vascular Scaffold (Abbott Vascular, Santa Clara, California) showed less luminal loss at the edges than luminal loss within the scaffold. The luminal reduction of both edges is not a nosologic entity, but an EVR in continuity with the SVR, extending from the in-scaffold margin to both edges. (ABSORB Clinical Investigation, Cohort B [ABSORB B]; NCT00856856)
Comparison of edge vascular response after sirolimus- and paclitaxel-eluting stent implantation
2013, International Journal of Cardiology
Citation Excerpt :
The TAXUS II study showed edge plaque progression in both the slow- and moderate-release groups, accompanied by lumen reduction at the proximal edge without remodeling [10]. Moreover, another study which compared proximal and distal edge effects after SES or PES implantation in patients with diabetes showed that PES implantation was associated with increased stent edge plaque progression accompanied by lumen reduction without remodeling [15]. In the present study, on the other hand, plaque progression with negative remodeling, which might not compensate the lumen reduction, was noted in both edge segments in the PES group, which resulted in increased edge restenosis.
To compare the edges vascular response, we analyzed the intravascular ultrasound (IVUS) parameters after implantation of the sirolimus-eluting stent (SES) or the paclitaxel-eluting stent (PES).
Two hundred-two angina patients (123 men; 61.5 ± 9.2 years of age, SES: n = 91, PES: n = 111) were enrolled. Both edge segments of the stent were analyzed. The change (Δ) of each parameter at follow-up was calculated.
The edge restenosis rate was higher in the PES group. However, the Δ Vessel, Δ Plaque and Δ Lumen volume at 5 mm edge segments were not different between the two groups except the Δ Plaque volume at the distal segment, higher in the PES than the SES group (6.6 ± 15.7 vs. 1.0 ± 13.1 mm³, P = .016). In the PES group, lumen area at the both 1 mm edge segments decreased because of plaque progression (proximal, 1.9 ± 1.5 to 2.2 ± 2.0 mm², P = .095; distal, 0.6 ± 1.1 to 1.0 ± 1.4 mm², P = .018) with negative remodeling (proximal, 9.9 ± 2.4 to 9.4 ± 2.6 mm², P = .004; distal, 7.6 ± 2.4 to 7.2 ± 2.4 mm², P = .052). Conversely, lumen area at these segments increased due to plaque regression (proximal, 3.2 ± 1.8 to 2.1 ± 1.6 mm², P = .000; distal, 1.5 ± 1.4 to 0.9 ± 1.3 mm², P = .000) even though there was negative remodeling in the SES group (proximal, 10.1 ± 2.4 to 9.6 ± 2.3 mm², P = .019; distal, 7.8 ± 2.3 to 7.5 ± 2.3 mm², P = .074). The Δ Plaque and Δ Lumen area at the both 1 mm edge segments were more prominent in the PES group.
Compared to SES, PES was associated with luminal reduction accompanied by plaque progression with negative remodeling at edge segments.
Edge vascular response after percutaneous coronary intervention
2013, JACC: Cardiovascular Interventions
Citation Excerpt :
Notably, the EEM remained unchanged at both stent edges. A lumen area increase of 0.4 ± 1.22 mm2 (p = 0.032) was observed only at the distal edge, which was due to a trend toward significant decrease of the plaque area from 5.8 to 5.6 mm2 (35). Diabetic patients have an aggressive form of atherosclerosis compared with non-diabetic persons with a higher risk of target lesion revascularization (TLR) due to angiographic restenosis.
The concept of edge vascular response (EVR) was first introduced with bare-metal stents and later with radioactive stents of various activity levels. Although radioactive stents reduced intra-stent neointimal hyperplasia and thereby the incidence of in-stent restenosis in a dose-dependent manner, tissue proliferation at the non-irradiated proximal and distal stent edges resulted in the failure of this invasive treatment. The advent of first- and second-generation drug-eluting stents (DES) reduced in-stent restenosis to approximately 5% to 10%, depending on the lesion subset and DES type. When in-segment restenosis (stent and 5-mm proximal and distal margins) occurred, it was most commonly focal and located at the proximal edge. In addition, stent thrombosis, the other main contributing factor for DES failure, seemed in part to be associated with residual plaque presence and underlying tissue composition at the landing zone of the implanted device, particularly if landed in a necrotic core rich milieu. More recently, the introduction of bioresorbable scaffolds for the treatment of coronary artery disease has prompted the re-evaluation of the EVR. This has recently been assessed up to 2-years after implantation of the Absorb bioresorbable vascular scaffold (Abbott Vascular, Santa Clara, California). In general, the EVR consists of a focal but significant proximal lumen loss that in a few instances necessitates target lesion revascularization of a flow-limiting edge stenosis. Herein, we provide an overview of the in vivo evaluation of the EVR with intravascular ultrasound, virtual histology intravascular ultrasound, and the more recently developed optical coherence tomography. Our objective is to highlight the clinical importance of the EVR as a predisposing and contributing factor to device failure with either bare-metal stents, DES, or bioresorbable scaffolds.
Meta-Analysis of Five Randomized Clinical Trials Comparing Sirolimus- Versus Paclitaxel-Eluting Stents in Patients With Diabetes Mellitus
2010, American Journal of Cardiology
Citation Excerpt :
Statistical analyses were performed using Stata version 9 (StataCorp LP, College Station, Texas). Of the 687 potentially relevant reports initially screened, a total of 8 trials (10 relevant reports) were initially identified.10–19 Two intravascular ultrasound studies10,11 were then excluded because no data were available on angiographic and clinical outcomes, and another trial12 was excluded because the SES and PES were simultaneously implanted in the same patient with diabetes with multiple coronary artery lesions, which precluded the ability to compare the clinical outcomes between the 2 different drug-eluting stents.
Recent data on drug-eluting stents have shown improved clinical outcomes in patients with diabetes mellitus. However, the relative efficacy and safety of sirolimus-eluting stents (SES) compared with paclitaxel-eluting stents (PES) remains controversial. Therefore, a meta-analysis of randomized trials was performed to compare SES with PES exclusively in patients with diabetes. The published research was scanned by formal searches of electronic databases (PubMed, EMBASE and the Cochrane Central Register of Controlled Trials) from January 2001 to April 2009. All randomized trials involving head-to-head comparison of SES versus PES in patients with diabetes were examined for analysis. A total of 5 randomized trials were included in the present meta-analysis, involving 1,173 patients (594 in the SES group, 579 in the PES group). SES were significantly more effective in the reduction of target lesion revascularization (5.1% vs 11.4%, odds ratio [OR] 0.41, 95% confidence interval [CI] 0.26 to 0.64, p <0.001) and angiographic binary (≥50%) restenosis (5.6% vs 16.4%, OR 0.30, 95% CI 0.19 to 0.48, p <0.001) compared to PES. In contrast, the differences between SES and PES were not statistically significant with respect to cardiac death (2.2% vs 2.9%, OR 0.71, 95% CI 0.34 to 1.47, p = 0.35), myocardial infarction (1.5% vs 2.6%, OR 0.58, 95% CI 0.26 to 1.31, p = 0.19), and stent thrombosis (0.6% vs 1.2%, OR 0.57, 95% CI 0.18 to 0.84, p = 0.35). In conclusion, SES are superior to PES in reducing the incidences of restenosis and target lesion revascularization in patients with diabetes, with nonsignificant differences in terms of cardiac death, myocardial infarction, and stent thrombosis.
Dye-Staining Angioscopy for Coronary Artery Disease
2015, Current Cardiovascular Imaging Reports

View all citing articles on Scopus

View full text

Coronary artery diseaseSerial Intravascular Ultrasound Analysis of Peri-Stent Remodeling and Proximal and Distal Edge Effects After Sirolimus-Eluting or Paclitaxel-Eluting Stent Implantation in Patients With Diabetes Mellitus

Section snippets

Methods

Results

Discussion

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol Interv

Am J Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Increased restenosis in diabetes mellitus after coronary interventions is due to exaggerated intimal hyperplasiaA serial intravascular ultrasound study

Circulation

Paclitaxel-eluting or sirolimus-eluting stents to prevent restenosis in diabetic patients

N Engl J Med

Randomized comparison of sirolimus-eluting stent versus standard stent for percutaneous coronary revascularization in diabetic patients: the Diabetes and Sirolimus-Eluting Stent (DIABETES) Trial

Circulation

Neointimal hyperplasia after sirolimus-eluting and paclitaxel-eluting stent implantation in diabetic patients: the Randomized Diabetes and Drug-Eluting Stent (DiabeDES) Intravascular Ultrasound Trial

Eur Heart J

Chronic arterial responses to polymer-controlled paclitaxel-eluting stents: comparison with bare metal stents by serial intravascular ultrasound analyses: data from the randomized TAXUS-II trial

Circulation

Coronary artery disease
Serial Intravascular Ultrasound Analysis of Peri-Stent Remodeling and Proximal and Distal Edge Effects After Sirolimus-Eluting or Paclitaxel-Eluting Stent Implantation in Patients With Diabetes Mellitus