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Journal of Endovascular Therapy
1 –9
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DOI: 10.1177/1526602815598753
www.jevt.org
Meta-analysis
Introduction
Atherosclerotic stenosis of the carotid artery constitutes a
major cause of ischemic stroke in the western world.1
Carotid endarterectomy (CEA) had been used as a proce-
dure for stroke prevention for many decades. The beneficial
role of CEA in preventing strokes, mostly for symptomatic
and to a lesser extent for asymptomatic patients, has been
highlighted in all current guidelines.2 In the era of less inva-
sive procedures, carotid artery stenting (CAS) has emerged
as an evolving alternative technique that may even be used
as the first-line treatment in high-risk patients.3
Randomized controlled trials comparing CEA and CAS
have produced diverging results.2 The safety and efficacy
of CAS have been debated, since some randomized trials
reported high complication rates within the CAS arm.3,4
On the contrary, several experienced centers continue to
report low rates of neurologic complications from large
CAS registries.5–7 These discrepancies between studies
may be the result of the operators’ learning curve, but it
also may be device-related.8
Carotid artery stenting can be performed with a number
of stents of different structural cell design (Table 1).
Different carotid stent designs create different vessel wall
scaffolding, and as a result their plaque stabilization
598753JETXXX10.1177/1526602815598753Journal of Endovascular TherapyKouvelos et al
research-article2015
1Department of Surgery, Vascular Surgery Unit, Medical School,
University of Ioannina, Greece
2First Department of Surgery, Vascular Surgery Unit, Medical School,
University of Athens, Greece
3Liverpool Vascular and Endovascular Service, Royal Liverpool University
Hospital, Liverpool, UK
4Third Department of Surgery, Vascular Surgery Unit, University of
Athens, Greece
Corresponding Author:
Miltiadis I. Matsagkas, Department of Surgery, Vascular Surgery Unit,
Medical School, University of Ioannina, Ioannina University Campus, S.
Niarchos Avenue, 45110 Ioannina, Greece.
Email: mimats@cc.uoi.gr
Meta-analysis of the Effect of Stent Design
on 30-Day Outcome After Carotid Artery
Stenting
George N. Kouvelos, MD, PhD1, Nikolaos Patelis, MD2,
George A. Antoniou, MD, PhD, FEBVS3, Andreas Lazaris, MD, PhD, FEBVS4,
and Miltiadis I. Matsagkas, MD, PhD, FEBVS1
Abstract
Purpose: To review the contemporary literature and analyze whether stent cell design plays a role in 30-day outcomes
after carotid artery stenting (CAS). Methods: A systematic review of the literature was undertaken that identified 9
studies comparing the effect of different cell design on 30-day outcome in patients undergoing CAS. Random-effects
models were applied to calculate pooled outcome data for mortality and cerebrovascular morbidity. Results are reported
as the odds ratio (OR) and 95% confidence interval (CI). Results: The 9 studies included 8018 patients who underwent
8028 CAS procedures (4018 open-cell stents, 4010 closed-cell stents). Six studies were retrospective in design, one was
a registry, and only two studies prospectively compared the effect of different cell designs. Nearly half of the patients
(3452, 43.1%) were symptomatic, with no significant difference between the closed- and open-cell stent groups (p=0.93).
During the first month after the procedure, there were no significant differences in mortality (OR 0.69, 95% CI 0.39 to
1.24, p=0.21), transient ischemic attacks (OR 0.95, 95% CI 0.69 to 1.30, p=0.74), or strokes (OR 1.17, 95% CI 0.83 to
1.66, p=0.37). Conclusion: This meta-analysis showed that 30-day cerebrovascular complications after CAS were not
significantly different for the open-cell group in comparison to the closed-cell group. Future prospective clinical trials
comparing different free cell areas and other stent design properties are still needed to further investigate whether stent
design plays a significant role in the results of carotid stenting.
Keywords
carotid artery stenting, closed cell, complications, open cell, mortality, stent design, stroke, transient ischemic attack
2 Journal of Endovascular Therapy
properties vary, mainly in relation to the size of the free cell
area between the struts of stents. Stents with small cell sizes
have a dense, metallic mesh, which in theory may provide
more effective plaque and wall coverage and reduce the risk
for embolization of particles compared to stents with larger
cell sizes. In one study, patients in the closed-cell arm
exhibited a substantially lower risk for neurologic adverse
events, supporting the hypothesis that stents with a small
free cell area and dense, metallic meshes improve the safety
of CAS.9 Closed-cell stents, however, are less flexible and
conformable to carotid anatomy and neck movement and
thus are perhaps not the best choice for specific groups of
patients.
In the absence of any clear evidence relating carotid
stent design and neurologic adverse events and mortality,
this study sought to review the literature concerning the
results of CAS using open- and closed-cell stents and evalu-
ate the 30-day mortality, stroke, and transient ischemic
attack (TIA) rates of each stent design.
Methods
Eligibility Criteria
The objectives, methodology of the systematic review and
analysis, and the inclusion criteria for study enrollment were
documented in a protocol that followed the PRISMA
(Preferred Reporting Items for Systematic reviews and Meta-
Analyses) guidelines. Studies comparing the effect of differ-
ent stent design on outcome of patients after CAS were
considered eligible; only comparative studies (open cell vs
closed cell) were included in the final analysis. Two reviewers
(G.N.K. and N.P.) performed eligibility assessment indepen-
dently in an unblended, standardized manner. Disagreements
between reviewers were arbitrated by discussion.
Search
An electronic search was conducted of the English-language
medical literature from 1991 to October 2014 using the
PubMed and EMBASE databases to find all studies com-
paring the effect of stent design on outcome of patients
undergoing CAS for carotid stenosis. Search terms included
“carotid,” “stenting,” “open cell,” “closed cell,” and “stent
design.” Related articles suggested by the PubMed search
engine and reviews on this subject were searched for addi-
tional relevant articles. Further articles were also identified
from the references cited in the initially identified reports.
The initial search identified 10 studies that compared the
effects of stent cell design on CAS outcome9–18; one study18
was excluded because the cohort was also included in a
later report.
Data Extraction
Two authors (G.N.K. and N.P.) independently extracted
data from the eligible full-text articles. Disagreements
between reviewers were resolved by consensus. The vari-
ables extracted from each article included: stent type, stent
models, patient age, gender, percent stenosis, symptom sta-
tus, use of an embolic protection device (EPD), use of pre/
post dilation, death, and cerebrovascular complications
(TIA and stroke).
Data Synthesis and Analysis
Binary outcome measures (occurrence of stroke, TIA, and
death) were calculated and reported as the odds ratio (OR)
and 95% confidence interval (CI). A fixed-effects model
was applied to calculate the pooled treatment effect. A
random-effects model was used in the event that significant
heterogeneity among the studies was identified. A forest
plot for each treatment effect was created. Inter-study het-
erogeneity was assessed visually using the forest plots.
Furthermore, heterogeneity was assessed using the Cochran
Q test (chi-square) and by measuring inconsistency (I) of
the effects of stent type; I2 values <50% was considered to
indicate low heterogeneity, 50% to 75% as moderate het-
erogeneity, and >75% as significant heterogeneity. A funnel
was constructed using the included studies to visually assess
any publication bias. Analyses were performed using the
Review Manager 5.2 (Cochrane Information Management
System; available at: http://ims.cochrane.org/revman)
Results
Study and Procedure Characteristics
The 9 studies that met the inclusion criteria included 8018
patients (mean age was 69.8±2.9 years; 5524 men) who
underwent 8028 CAS procedures using 4018 open-cell and
4010 closed-cell stents (Table 2).9–17 Six studies were retro-
spective, one was a registry, and only 2 studies prospec-
tively compared the effect of different cell designs. The size
Table 1. Types of Stents Used for Carotid Artery Stenting.
Design Stent Free Cell Area, mm2
Closed cell Wallstent 1.08
Xact 2.74
NexStent 4.07
Adapt 4.4
Open cell Precise 5.89
Exponent 6.51
Protégé 10.71
Acculink 11.48
Hybrid Cristallo 3.24–15.17
Kouvelos et al 3
of the patient cohort in each study ranged from 40 to 3179,
and the period during which these studies were published
was from 2007 to 2013. Nearly half of the patients (3452,
43.1%) were symptomatic, with no significant difference
between the open-cell (44.4%) and closed-cell (41.7%)
groups (p=0.93).
The procedure characteristics are summarized in Table 3.
An EPD was used in the vast majority of the procedures
(90.7%), with no significant differences between the 2
groups (p>0.05). Data on the exact stent model were avail-
able in half of the study’s cohort (4022, 50.3%; 1418 open-
cell stents and 2604 closed-cell stents). In the open-cell
group, the most frequently deployed stent was the Acculink
(Guidant, Santa Clara, CA, USA; 540 stents, 38.1%) fol-
lowed by Protégé (Medtronic/Covidien, Minneapolis, MN,
USA; 381 stents, 26.9%), and Precise (Cordis, Miami, FL,
USA; 369 stents, 26.4%). In the closed-cell group, the
majority of the stents used were Wallstents (Boston
Scientific, Marlborough, MA, USA; 2252 stents, 88.3%).
Data on pre- and postdilation frequency were clearly
reported in 5 studies. No significant differences were noted
between the two groups either in prestent (p=0.75) or post-
stent dilation frequencies (p=0.99).
The relation of symptoms with 30-day cerebrovascular
outcome and stent design was investigated in 4 studies
(Table 4). Only 2 of these studies gave detailed data for
30-day outcome; the other 2 indicated only that there were
no statistically significant differences in cerebrovascular
events between symptomatic and asymptomatic patients
receiving open-cell or closed-cell stents. In the study by
Bosiers et al,9 the differences in postprocedure event rates
were highly pronounced among symptomatic patients
(p<0.0001).
Perioperative Outcomes
Data on 30-day mortality were extracted from all studies
(Table 5). No significant differences were found between the
groups (OR 0.69, 95% CI 0.39 to 1.24, p=0.21; Figure 1).
No significant heterogeneity among the studies existed
(I2=0%). Visual evaluation of the funnel plot suggested that
the possibility of publication bias was low (Figure 2).
All 9 studies concerning 8028 procedures reported the
occurrence of cerebrovascular events (stroke plus TIA) dur-
ing the 30 days after the procedure (Table 5). No significant
differences in TIA were noted between the different stent cell
designs (OR 0.95, 95% CI 0.69 to 1.30, p=0.74; Figure 3).
Moderate heterogeneity among the studies was indicated
(I2=66%), and no asymmetry in the funnel plot was found to
indicate any significant publication bias (Figure 2).
The incidence of stroke was similar in the open-cell (87,
2.2%) vs closed-cell (61, 1.5%) groups (OR 1.17, 95% CI
0.83 to 1.66, p=0.37; Figure 4). Heterogeneity among stud-
ies was insignificant (I2=16%), and the probability of pub-
lication bias was low (Figure 2). Similarly, when analysis
was performed for all cerebrovascular events occurring
Table 2. Study and Patient Characteristics According to Stent Cell Design.
First
Author,
Year
Study
Type n
Stent Cell Type Age, yaMenbStenosis, %aSymptomsb
Open Closed Open Closed Open Closed Open Closed Open Closed
Bosiers,
2007
R 3179 937 2242 72.8±1 70.7±1.5 NR NR NR NR 383
(41)
934
(42)
Schillinger,
2008
R 1684 825 859 71
(64–78)
72
(64–77)
524
(63)
599
(70)
85
(80–90)
85
(80–90)
381
(46)
293
(34)
Maleux,
2009
R 123 60 72 74.9±5.1 74.3±6.9 44
(73)
52
(72)
NR NR 19
(32)
35
(49)
Timaran,
2011
P 40 20 20 67
(60–75)
65
(59–71)
20
(100)
20
(100)
NR NR 9
(45)
8
(40)
Jim, 2011 Reg 2322 1775 547 NR NR NR NR NR NR 796
(45)
265
(48)
Grunwald,
2011
R 120 84 36 68.9±1 66.5±1.4 NR NR 88 86 25
(30)
7
(19)
Tadros,
2012
R 173 125 48 70.0±8.6 73.4±10.2 70
(56)
31
(65)
87.2±8 90.6±7.8 48
(38)
15
(52)
Sahin, 2013 R 282 144 138 66.6±9.2 66.6±8.3 102
(71)
110
(80)
83.6±11.6 86.8±10.8 86
(60)
72
(52)
Park, 2013 P 96 48 48 69.1±7.5 68.8±7.7 43
(90)
36
(75)
40% >70% 41% >70% 36
(75)
40
(83)
Abbreviations: NR, not reported; P, prospective; R, retrospective; Reg, registry.
aData are presented as the means ± standard deviation or median (range).
bData are given as the counts (percentage).
4 Journal of Endovascular Therapy
within 30 days of treatment, including both strokes and
TIAs, no significant differences between open- and closed-
cell stent design were demonstrated when a fixed effects
model was applied (OR 1.05, 95% CI 0.83 to 1.33, p=0.69;
Figure 5). The between-study heterogeneity was moderate
(I2=65%), whereas the funnel plot did not indicate signifi-
cant publication bias (Figure 2). The combined incidence
of cerebrovascular events and death was also similar
between the two groups (OR 1, 95% CI 0.8 to 1.25, p=0.98;
Figure 6), while no significant publication bias was
depicted from the funnel plot (Figure 2).
Discussion
Carotid stents have sequentially aligned annular rings inter-
connected by bridges.17 The number and arrangement of
these bridge connectors differentiate open-cell from closed-
cell designs.19 Closed-cell stents are characterized by
smaller free cell areas between struts, thus leaving smaller
gaps uncovered.11 These stents are rigid and may be prone
to kinking, while more flexible open-cell stents conform
better to tortuous anatomy. Theoretically, closed-cell stents
are characterized by an improved ability to scaffold plaque,
Table 3. Procedure Characteristics According to Stent Cell Design.
First Author,
Year n
EPD UsageaStent TypeaPre/Post Stent Dilationa
Open Closed Open Closed Open Closed
Bosiers, 2007 3179 921 (98) 2128 (95) Precise: 293 (31)
Protégé: 201 (21)
Acculink: 409 (44)
Exponent: 34 (4)
Wallstent: 2107
(94)
Xact: 105 (5)
NexStent: 30 (1)
NR NR
Schillinger, 2008 1684 730 (89) 744 (84) NR NR 432 (52) / 814 (99) 674 (79) / 854 (99)
Maleux, 2009 123 46/60 10/72 Acculink: 37 (62)
Precise: 18 (30)
Exponent: 5 (8)
Wallstent: 72 (100) NR NR
Timaran, 2011 40 20 (100) 20 (100) Acculink: 20 (100) Xact: 20 (100) 18 (90) / 20 (100) 16 (80) / 20 (100)
Jim, 2011 2322 NR NR NR NR NR NR
Grunwald, 2011 120 0 (0) 0 (0) Zilver: 84 (70) Wallstent: 36 (30) NR / 84 (100) NR / 36 (100)
Tadros, 2012 173 125 (100) 48 (100) Precise: 15 (8)
Protégé: 36 (21)
Acculink: 74 (43)
Wallstent: 37 (21)
Xact: 8 (5)
NexStent: 3 (2)
NR NR
Sahin, 2013 282 144 (100) 138 (100) All Protégé All Xact 16 (11) / 128 (89) 28 (20) / 127 (92)
Park, 2013 96 43 (90) 48 (100) All Precise All Wallstent 41 (85) / 48 (100) 43 (90) / 48 (100)
Abbreviations: EPD, embolic protection device; NR, not reported.
aData are given as the counts (percentage).
Table 4. Outcome of the Study Population According to Treatment Indication.
Open CellaClosed Cella
First Author, Year Symptomatic Asymptomatic Symptomatic Asymptomatic
Bosiers, 2007 21 (5.5) events 12 (2.3) events 27 (2.9) events 30 (2.3) events
Schillinger, 2008 No difference stated, but no detailed data given
Maleux, 2009 No difference stated, but no detailed data given
Timaran, 2011 NR NR NR NR
Jim, 2011 Stroke: 29 (3.6) 16 (1.6) 5 (1.9) 4 (1.4)
TIA: 19 (2.4) 9 (0.9) 6 (2.3) 4 (1.4)
Mort: 10 (1.3) 15 (1.5) 6 (2.3) 4 (1.4)
Grunwald, 2011 NR NR NR NR
Tadros, 2012 NR NR NR NR
Sahin, 2013 NR NR NR NR
Park, 2013 NR NR NR NR
Abbreviations: NR, not reported; TIA, transient ischemic attack; Mort: mortality
aData are given as the counts (percentage of the subgroup in the column).
Kouvelos et al 5
thus reducing embolization in patients of high embolic
risk.9,16 However, the scaffolding benefits of a closed-cell
design have a cost in flexion and conformability, just as the
flexion benefits of an open-cell design have a cost in scaf-
folding uniformity.
In most CAS procedures, either open-cell or closed-cell
stents may be used.20 The reports of the effect of stent
design on cerebrovascular outcome have been controver-
sial, and the theoretic advantage of plaque stabilization by
the closed-cell stents has not been clinically established.
While stent design may (albeit subtly) impact rates of TIA
or stroke, it is unlikely that it can impact mortality, though
some strokes may result in death. In 2006, Hart et al18 sug-
gested for the first time that carotid stents with a closed-cell
design seem to be superior to those with open-cell design
regarding 30-day stroke and death rate. In a consequent
multicenter, retrospective, observational study, the same
authors expanded their initial series to include 3179 CAS
procedures.9 The postprocedure event rates varied from
1.2% to 5.9% for free cell areas of 2.5 and 6.5 mm2, respec-
tively (p<0.05). To the contrary, these results were not con-
firmed in a later study of 1700 patients.15 In this study,15
open-cell carotid stent design was not associated with an
increased risk for combined neurologic complications com-
pared with closed-cell stent (open-cell 6.1% vs closed-cell
4.1%, p=0.077), though the statistical insignificance was
marginal.15 This disagreement between these 2 large studies
may reflect differences in treatment strategies and patient
selection between different centers and countries. In the
present review encompassing nearly 8000 patients, the rates
of stroke, death, and TIA during the first 30 days after the
procedure were not different in patients receiving either
open- or closed-cell carotid stents. Therefore, our results do
not support the superiority of a specific stent cell design
with respect to cerebrovascular complications and mortality
risk.
Cerebral embolization has been used as a surrogate
endpoint to compare different effects of CEA and CAS. A
Table 5. Outcomes of the Study Population by Stent Cell Design.
Mortality at 30 DaysaTIAaStrokea
First Author, Year Open Closed p Open Closed p Open Closed p
Bosiers, 2007 2 (0.2) 5 (0.2) NR 25 (2.7) 24 (1.1) NR 11 (1.2) 22 (1) NR
Schillinger, 2008 0 (0) 1 (0.01) NR 14 (1.7) 35 (4.1) NR 21 (2.4) 26 (3) NR
Maleux, 2009 0 (0) 1 (1.4) NR 2 (3.3) 2 (2.8) NR 4 (6.7) 1 (1.4) NR
Timaran, 2011 0 (0) 0 (0) NR 1 (5) 0 (0) NR 1 (5) 0 (0) NR
Jim, 2011 25 (1.4) 10 (1.8) 0.54 32 (1.8) 13 (2) 0.7 45 (2.5) 9 (1.6) 0.25
Grunwald, 2011 1 (1.2) 0 (0) NR 3 (3.6) 1 (2.8) NR 1 (1.2) 0 (0) NR
Tadros, 2012 1 (0.8) 0 (0) 0.54 0 (0) 0 (0) NR 0 (0) 2 (4.2) 0.16
Sahin, 2013 0 (0) 2 (1.4) 0.14 5 (3.5) 5 (3.6) 0.94 4 (2.8) 0 (0) 0.04
Park, 2013 0 (0) 1 (2.1) 1 0 (0) 2 (4.3) 0.49 0 (0) 1 (2.1) 1
Abbreviations: NR, not reported; TIA, transient ischemic attack.
aData are given as the counts (percentage of the cell type).
Figure 1. Differences in 30-day mortality rate between the open-cell and closed-cell groups.
6 Journal of Endovascular Therapy
substudy of the International Carotid Stenting Study
looked at 124 CAS and 107 CEA patients and reported
about three times more patients in the stenting group than
in the endarterectomy group having ischemic lesions on
diffusion-weighted (DW) imaging.21 The effect of stent
design on cerebral embolization after CAS has not been
sufficiently studied so far. In theory, an open-cell structure
would increase the risk of plaque material extruding
through the stent interstices. Still, in a prospective ran-
domized study of 40 patients, Timaran et al17 found that
cerebral embolization, as depicted in DW magnetic
resonance imaging, occurs with similar frequency after
CAS with open- and closed-cell stents. On the contrary,
Park et al13 found that open-cell stents are associated with
more frequent formation of new lesions on DW imaging
after the procedure compared to closed-cell stents.
Furthermore, Grunwald et al10 reported that open-cell
stents were related to a lower number and area of silent
cerebral ischemic lesions in nearly 200 patients after
unprotected CAS. However, clinical outcome, measured
by incidence of adverse events and clinical neurologic
assessment, in all these studies was not significantly
Figure 2. Funnel plots for (A) 30-day mortality, (B) transient ischemic attack, (C) stroke, and (D) cerebrovascular events.
Figure 3. Differences in transient ischemic attack rate between the open-cell and closed-cell groups.
Kouvelos et al 7
different between patients with different stent designs,
implying that these clinically silent embolic lesions do not
affect cerebrovascular outcome.
Overall neurologic complication rates varied between
studies, ranging from 0% to 6.7%. This may reflect differ-
ences in patient selection and treatment strategies between
Figure 4. Differences in stroke rate between the open-cell and closed-cell groups.
Figure 5. Differences in cerebrovascular events (stroke plus transient ischemic attack) between the open-cell and closed-cell groups.
Figure 6. Differences in all events (death, stroke, transient ischemic attack) between the open-cell and closed-cell groups.
8 Journal of Endovascular Therapy
centers and countries. Certain parameters, such as postdila-
tion frequency, oversizing rates, technical difficulties, and
accurate timing of the events in relation to different phases
of the procedure, have not been adequately reported and
accounted in the majority of studies, probably due to their
retrospective nature. Embolic debris can potentially be gen-
erated at multiple stages, including during wire and catheter
passage, EPD and stent deployment, and pre- or postdila-
tion. Future studies should focus on investigating other pro-
cedure parameters besides device characteristics that may
affect outcome after CAS.
The present study supports the view that closed-cell
stents do not improve the safety of CAS by providing
increased wall coverage and optimal plaque stabilization.
However, the large differences in free cell area, even in
stents of the same group, should be acknowledged. For
example, there is a large difference in free cell area between
Wallstent (1.08 mm2) and NexStent (4.07 mm2) of the
closed-cell group, as well as between Precise (5.69 mm2)
and Acculink (11.48 mm2) of the open-cell group. These
differences were taken into account in only one study. By
directly comparing Wallstent (the smallest free cell area) to
the Acculink stent system (the largest free cell area),
Shillinger et al15 found that the observed differences became
even smaller than in the entire patient sample. Other stent-
related factors may be relevant determinants of cerebrovas-
cular outcome and certainly need further investigation.
The vast majority of the patients in this review under-
went CAS under an EPD, which could have influenced the
role of stent design in distal embolization during the proce-
dure. CAS without an EPD has already been investi-
gated.22,23 In subgroup analyses, the complication rates for
protected vs unprotected groups in SPACE 1 showed 8.3%
vs 6.5%.24 Several reports pointed out that EPDs do not
completely eliminate the risk of cerebral embolization.25
Notably, distal vasospasm and slow flow are described with
incidences of up to 3.6% and 7.2%, respectively.26 Lesion-
related CAS with closed-cell design stents without an EPD
has also been proven effective, especially when individual
anatomical variance was considered.27 The association of
stent design with clinical outcome and radiological findings
after unprotected CAS has been investigated in only one
retrospective study of 194 patients treated between 2000
and 2006.10 However, currently, an EPD constitutes an inte-
gral part of the CAS procedure. Therefore, the design of a
study without embolic protection to investigate the exact
effect of cell area on distal embolization is impossible due
to ethical and regulatory considerations.
The relationship of symptomatic carotid artery lesions
and stent design has been investigated in only 4 studies,
producing diverging results. Detailed data were available in
only two of these studies, so no reliable analysis could be
performed. Jim et al11 found that symptomatic patients had
a higher stroke rate in-hospital for both the open- and
closed-cell patients, with no differences when comparing
the 2 stent designs. This finding has also been confirmed in
other 2 studies.12,15 On the contrary, in the Belgium-Italian
(BIC) Registry, the difference between designs was primar-
ily seen in symptomatic patients.9 This finding has been
partially supported in a prospective study by Park et al,13
who found that new lesions on postoperative DW images
were noted more frequently in the open-cell–stented symp-
tomatic patients, without, however, having any effect on
clinical outcome when comparing the two groups.
Nevertheless, none of these studies was randomized, and
stent selection according to physician preference may have
certainly influenced their results.
The present meta-analysis associates data across studies
to estimate treatment effects of stent design on cerebrovas-
cular outcome after CAS with more precision than is pos-
sible in a single study. Unfortunately, very few studies
report on the adjusted risk ratio for specific outcomes, thus
pooling adjusted risk estimates, although more appropriate,
was not possible. The main limitation of this review is that
only 2 of 9 studies were prospective. The results are based
mostly on synthesis of outcomes of observational retrospec-
tive studies with varied methodological quality and no
detailed 30-day data. However, based on the results of the
present meta-analysis, any randomized trial investigating
the differences of cell design would be underpowered unless
it is designed to include thousands of patients. Selection
bias for specific stents in specific anatomic and clinical set-
tings is evident, since the open-cell design is known to be
more flexible and therefore more likely to be used in kinked
morphologies, while closed-cell stents are more rigid and
thus better suited for straight lesions. Moreover, in most
studies, different devices are grouped within each category
of open- or closed-cell stents; therefore, risks for device-
specific complications have not been adequately studied.
Conclusion
There is continuous refinement in CAS techniques based on
selection of different endovascular devices for varying ana-
tomic and plaque characteristics. Selection of the stent
design should be incorporated into CAS treatment plan-
ning. This meta-analysis showed that 30-day cerebrovascu-
lar complications after CAS are not significantly different
for the open-cell stents in comparison to the closed-cell
stents. Future prospective clinical trials comparing different
free cell areas and other stent design properties are still
needed to further investigate whether stent design consti-
tutes a way to improve the results of CAS.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this
article.
Kouvelos et al 9
Funding
The author(s) received no financial support for the research,
authorship, and/or publication of this article.
References
1. Rosamond W, Flegal K, Friday G, et al. Heart disease and
stroke statistics—2007 update: a report from the American
Heart Association Statistics Committee and Stroke Statistics
Subcommittee. Circulation. 2007;115:69–71.
2. Paraskevas KI, Mikhailidis DP, Veith FJ. Comparison of the
five 2011 guidelines for the treatment of carotid stenosis. J
Vasc Surg. 2012;55:1504–1508.
3. Ringleb PA, Allenberg J, Bruckmann H, et al. 30 day results
from the SPACE trial of stent-protected angioplasty versus
carotid endarterectomy in symptomatic patients: a randomised
non-inferiority trial. Lancet. 2006;368:1239–1247.
4. EVA-3S Investigators. Endarterectomy versus stenting in
patients with symptomatic severe carotid stenosis. N Engl J
Med. 2006;355:1660–1671.
5. Boltuch J, Sabeti S, Amighi J, et al. Procedure-related com-
plications and neurological adverse events after protected
vs. unprotected carotid stenting. J Endovasc Ther. 2005;12:
538–547.
6. Biggs NG, Rangarajan S, McClure DN. Has carotid artery
stenting found its place? A 10-year regional centre per-
spective [published online January 24, 2014]. ANZ J Surg.
doi:10.1111/ans.12517.
7. Cremonesi A, Gieowarsingh S, Spagnolo B, et al. Safety,
efficacy and long-term durability of endovascular therapy for
carotid artery disease: the tailored-Carotid Artery Stenting
Experience of a single high-volume centre (tailored-CASE
Registry). EuroIntervention. 2009;5:589–598.
8. Ahmadi R, Willfort A, Lang W, et al. Carotid artery stenting:
effect of learning curve and intermediate-term morphological
outcome. J Endovasc Ther. 2001;8:539–546.
9. Bosiers M, de Donato G, Deloose K, et al. Does free cell area
influence the outcome in carotid artery stenting? Eur J Vasc
Endovasc Surg. 2007;33:135–141.
10. Grunwald IQ, Reith W, Karp K, et al. Comparison of stent free
cell area and cerebral lesions after unprotected carotid artery
stent placement. Eur J Vasc Endovasc Surg. 2012;43:10–14.
11. Jim J, Rubin BG, Landis GS, et al; SVS Outcomes Committee.
Society for Vascular Surgery Vascular Registry evaluation of
stent cell design on carotid artery stenting outcomes. J Vasc
Surg. 2011;54:71–79.
12. Maleux G, Marrannes J, Heye S, et al. Outcome of carotid
artery stenting at 2 years follow-up: comparison of nitinol
open cell versus stainless steel closed cell stent design. J
Cardiovasc Surg (Torino). 2009;50:669–675.
13. Park KY, Kim DI, Kim BM, et al. Incidence of embolism
associated with carotid artery stenting: open-cell versus
closed-cell stents. J Neurosurg. 2013;119:642–647.
14. Sahin M, Açar G, Ozkan B, et al. Comparison of short-term
outcomes after carotid artery stenting according to differ-
ent stent designs. Postepy Kardiol Interwencyjnej. 2013;9:
121–125.
15. Schillinger M, Gschwendtner M, Reimers B, et al. Does
carotid stent cell design matter? Stroke. 2008;39:905–909.
16. Tadros RO, Spyris CT, Vouyouka AG, et al. Comparing the
embolic potential of open and closed cell stents during carotid
angioplasty and stenting. J Vasc Surg. 2012;56:89–95.
17. Timaran CH, Rosero EB, Higuera A, et al. Randomized clini-
cal trial of open-cell vs closed-cell stents for carotid stenting
and effects of stent design on cerebral embolization. J Vasc
Surg. 2011;54:1310–1316.
18. Hart JP, Peeters P, Verbist J, et al. Do device characteris-
tics impact outcome in carotid artery stenting? J Vasc Surg.
2006;44:725–730.
19. Siewiorek GM, Finol EA, Wholey MH. Clinical significance
and technical assessment of stent cell geometry in carotid
artery stenting. J Endovasc Ther. 2009;16:178–188.
20. Müller-Hülsbeck S, Preuss H, Elhöft H. CAS: which stent for
which lesion. J Cardiovasc Surg (Torino). 2009;50:767–772.
21. Bonati LH, Jongen LM, Haller S, et al; ICSS-MRI Study
Group. New ischaemic brain lesions on MRI after stenting or
endarterectomy for symptomatic carotid stenosis: a substudy
of the International Carotid Stenting Study (ICSS). Lancet
Neurol. 2010;9:353–362.
22. Müller-Hülsbeck S. Commentary: Experimental, ex vivo, and
bench testing to evaluate embolic/distal protection devices:
useful or wasteful? J Endovasc Ther. 2012;19:261–262.
23. Müller-Hülsbeck S, Schäfer PJ, Hümme TH, et al. Embolic
protection devices for peripheral application: wasteful or use-
ful? J Endovasc Ther. 2009;16:163–169.
24. Tietke M, Jansen O. Cerebral protection vs no cerebral protec-
tion: timing of stroke with CAS. J Cardiovasc Surg (Torino).
2009;50:751–760.
25. Müller-Hülsbeck S, Grimm J, Liess C, et al. Comparison
and modification of two cerebral protection devices used
for carotid angioplasty: in vitro experiment. Radiology.
2002;225:289–294.
26. Reimers B, Corvaja N, Moshiri S, et al. Cerebral protection
with filter devices during carotid artery stenting. Circulation.
2001;104:12–15.
27. Hopf-Jensen S, Marques L, Preiß M, et al. Lesion-related
carotid angioplasty and stenting with closed-cell design with-
out embolic protection devices in high-risk elderly patients—
can this concept work out? A single center experience
focusing on stent design. Int J Angiol. 2014;23:263–270.
