Keywords carotid artery - ischemic - stenosis - stroke - cardiovascular diseases
Introduction
Worldwide, cardiovascular diseases (CVDs) are considered among the leading causes
of mortality. Compared with Europeans, Indians are affected a decade earlier in their
most productive midlife years. Nearly 52% of deaths in India before the age of 70
years are due to CVD, whereas 23% of deaths happen in Western countries.[1 ] Increased prevalence of CVD and its related risk factors had led to this epidemiological
transition in India. In 2016, 54.5 million was the estimated prevalence of CVDs. Presently,
more than 80% of deaths in India are because of CVDs with ischemic heart disease and
stroke.[2 ]
Stroke is a major global public health problem and is a common among various CVDs.
Global Burden of Diseases considers stroke as the second leading cause of death and
major cause of disability worldwide.[3 ] Almost 20% of strokes across the globe are due to atherosclerotic stenosis of the
extracranial carotid artery. The diagnosis and treatment of carotid artery disease
have improved significantly over the past two decades with the emergence of medical
treatment and carotid revascularization procedures. Both carotid artery endarterectomy
(CEA) and carotid artery angioplasty with stenting (CAAS) are recommended for symptomatic
patients with 50% or more stenosis or asymptomatic patients with 70% or more stenosis.[4 ]
For the past three decades, carotid artery stenting (CAS), an alternative to CEA,
has been used for carotid artery stenosis revascularization. Interventionalists are
experiencing increased technical developments in arterial stents and neuroprotection
for CAS deployment. Comparative studies have reported varied patient outcomes, health
status, major and minor complications, and health-related quality of life regarding
the effectiveness of the CAS and CEA.[5 ]
Evidence shows that postprocedural plaque protrusion (PP) through the stent struts,
which occurs in 30 to 100% of conventional carotid stents depending on the plaque
type and imaging technique used, is not benign.[6 ] One fundamental difference between the open surgical and endovascular methods of
carotid revascularization is that by removing the plaque, CEA eliminates the postprocedural
problems of the plaque. In contrast, conventional CAS does not remove plaque but seeks
to stabilize the potentially embolic lesion by covering it with a layer of the metallic
stent and subsequent stable fibrous tissue layer (healing).[7 ]
One of the major causes of ischemic complications after stent deployment in patients
with unstable plaques is PP through stent struts. Open-cell stent devices have a higher
risk of periprocedural stroke compared with closed-cell devices.[8 ] PP can be reduced by using recently developed new-generation double-layer, thin-strut
nitinol stents with a mesh covering that traps and exclude thrombus and plaque debris.[9 ] The superiority of micromesh stents compared with conventional stents for CAS has
been reported by clinical studies with good short- to medium-term follow-up results.
In Japan, a clinical trial using the micromesh stent has been performed that reduced
postprocedure ischemic complications.[10 ]
Literature related to mechanical properties of single-layer and double-layer stents,
stent design, and their deployment causing procedural ipsilateral stroke risk after
treatment is unclear. A better understanding of different stents deployment in facilitating
clinical choice and further enhancing the productivity of life is needed in developing
countries like India. Therefore, we aimed to compare the clinical outcome and efficacy
of single-layer and dual-layer mesh stent for CAS among carotid stenosis patients.
Aims and Objectives
The aim of this article was to compare the clinical outcome and efficacy of single-layer
versus dual-layer mesh stent for CAS among carotid stenosis patients.
Materials and Methods
Study Design
A prospective observational study was conducted among 41 patients undergoing CAS for
carotid stenosis in the department of interventional radiology in a tertiary care
setting. The study was conducted for a period of 2 years, from November 2019 to November
2021.
Sample Size
In our pilot study results with 10 cases in each group we found that the minimum clinical
important difference in proportion of reclusion rate between single-layer and double-layer
stent groups was 37%. Hence considering 80% power of the study and 5% α error 19 cases
in each group was the our sample size. Based on availability of dual-layer group,
three more cases were included and hence the sample size included in study was 41
participants. The formula used for sample size calculation was.[11 ]
N : Sample Size
π
1 , π
0 : Proportion
U : One-sided percentage point of the normal distribution corresponding to 100%—the
power
power is = 80%, u =0.84
V : Percentage point of the normal distribution corresponding to the (two-sided) significance
level, e.g., if significance level = 5%, v = 1.96
Single-layer stent group (N = 19)
Dual-layer stent group (N = 22)
Inclusion Criteria
➢ Symptomatic patients showing ≥50% stenosis of the internal carotid artery (ICA).
➢ Asymptomatic patients showing ≥80% stenosis of the ICA.
➢ Patients with more than 5 years life expectancy.
Exclusion Criteria
➢ Simultaneous contralateral stenosis or occlusion of the ICA.
➢ Uncorrectable bleeding diathesis.
➢ Allergy to antiplatelet medication and metals in-stent (nickel, titanium, cobalt,
chromium).
➢ Recent intracranial hemorrhage.
➢ Intracranial aneurysm.
➢ Patients with acute stroke.
Data Collection
All procedures were performed under conscious sedation. A biplane angiography system
(Allura Xper, Phillips, the Netherlands) was used for the endovascular procedures.
All patients received DAPT with aspirin and clopidogrel at least 5 days prior to intervention
and a loading dose of oral ticagrelor 90 mg on the day of the procedure. Using Seldinger's
technique, retrograde common femoral arterial access was obtained, and diagnostic
carotid and a cerebral angiogram were performed. The diagnostic catheter was exchanged
for 6F Neuro Max guiding catheter (Penumbra Inc.), which was placed in mid-common
carotid artery (CCA). An exchange length guidewire was navigated through the narrowed
segments of distal CCA and carotid bulb into the petrous ICA. Whenever possible embolic
protection device was navigated by over the wire technique and deployed 3 cm distal
to the carotid bulb in distal cervical ICA. Prestenting angioplasty was performed
in cases where the stent placement had difficulty in directly advancing over the lesion.
Then, the carotid stent system was tracked over the bare wire of the embolic protection
device and deployed from the proximal cervical ICA up to the proximal CCA to completely
cover the plaque. If necessary, poststenting angioplasty was done.
Patients were kept under DAPT with aspirin (75 mg once daily) and ticagrelor (90 mg
twice daily) for the 6-month postinterventional period. They received a lipid-lowering
medication, and cerebrovascular risk factors such as hypertension and diabetes were
controlled and medically treated.
Stents used in single-layer stent group were X Act, Wall, and Acculink stents.
C Guard stent is used in all patients of dual-layer stent group.
Imaging
Preprocedure all patients underwent computed tomographic neck and cerebral angiography
for the exact assessment of the carotid stenosis according to the North American symptomatic
carotid endarterectomy trail (NASCET) criteria.
Operational Definitions
Patients with amaurosis fugax, hemispheric transient ischemic attack (TIA), or ipsilateral
ischemic stroke without major disability (National Institutes of Health Stroke Scale]
score <15, modified Rankin Scale [mRS] score >3) were considered symptomatic if these
events occurred in the 6 months before intervention. The mRS is used for assessing
general daily life functionality and independence (with ≤ 2 defined as independence).
Patients were classified as high risk if they met at least 1 of the below criteria:
Clinically (age >80 years, Canadian Cardiovascular Society class III or IV angina
or unstable angina, congestive heart failure [New York Heart Association functional
class III or IV]),
Left ventricular ejection fraction less than 30%,
Severe stenosis of the common coronary artery of the left or 2 or more epicardial
coronary arteries,
Need for cardiac surgery in less than 30 days,
Recent myocardial infarction and severe chronic lung disease,
Anatomic abnormalities (high cervical lesions, sub clavicular lesions, previous radical
neck surgery or radiotherapy treatment, restenosis after CEA, obstruction of the carotid
contra-lateral, tracheostomy, and paralysis of the larynx and the contralateral nerve).[12 ]
Study Variables
Procedural efficacy and complication were considered as the primary outcome variable.
Mortality rate and favorable clinical outcome—defined as mRS score less than or equal
to 2 within 30 days—were secondary outcome variables.
Statistical Analysis
All quantitative variables were presented as mean and standard deviation and categorical
variables as frequency and proportions. Categorical outcomes were compared between
study groups using the chi-squared test. p -Value less than 0.05 was considered statistically significant. SPSS version 22 was
used for statistical analysis.[13 ]
Results
A total of 41 subjects were included in the final analysis with a follow-up of 30
days.
Mean age of study population in dual-layer stents group was 63.86 ± 11.08 years and
it was 61.47 ± 8.26 years in single-layer stent group. Prestent angioplasty was performed
in eight (42.11%) participants of in single-layer group and only four (18.18%) participants
in dual-layer stent group where poststenting angioplasty was done in almost equal
participants in both groups (94.74% in single layer and 95.45% in double layer). There
was no statistically significant difference between two groups in other baseline parameters
like age, stenosis, side of stenosis, prestenting angioplasty and poststenting angioplasty
(p -value >0.05)([Table 1 ]).
Out of 22 participants with dual-layer stent, only 1 participant experienced five
episodes of TIA in last one (4.55%) month with free floating thrombus. Both clinical
and associated complaints were more in dual-layer group compared with single layer
([Table 2 ]).
Table 1
Comparison of baseline parameter between study group (n = 41)
Parameter
Study group
p -Value
Single-layer stents
(n = 19)
Dual-layer stents
(n = 22)
Age (in years)
61.47 ± 8.26
63.86 ± 11.08
0.445[a ]
Stenosis
0.8 (0.8,0.9)
0.8 (0.7,0.9)
0.733[b ]
Side of stenosis
Left
14 (73.68%)
14 (63.64%)
0.491[c ]
Right
5 (26.32%)
8 (36.36%)
Used stent
Acculink
1 (5.26%)
0 (0%)
[
d
]
C Guard
0 (0%)
22 (100%)
Wall
9 (47.37%)
0 (0%)
X Act
9 (47.37%)
0 (0%)
Filter
Emboshield
4 (21.05%)
0 (0%)
[
d
]
Filter Wire EZ
7 (36.84%)
2 (9.09%)
Spider FX
7 (36.84%)
5 (22.73%)
No
1 (5.26%)
15 (68.18%)
Prestenting angioplasty
8 (42.11%)
4 (18.18%)
0.093[
c
]
Poststenting angioplasty
18 (94.74%)
21 (95.45%)
1.000[
e
]
Abbreviations: FW, Filter Wire.
a Independent sample t -test.
b Mann–Whitney U test.
c Chi-squared test.
d No statistical test was applied due to 0 subjects in the cells.
e Fisher's exact test.
Table 2
Comparison of clinical complaints between study group (n = 41)
Clinical complaints
Study group[a ]
Single-layer stents (n = 19)
Dual-layer stents (n = 22)
Five episodes of transient ischemic attack in last 1 month with free floating thrombus
0 (0%)
1 (4.55%)
Acute left watershed infarcts
1 (5.26%)
1 (4.55%)
Right limb weakness
0 (0%)
1 (4.55%)
Blurring of vision
1 (5.26%)
2 (9.09%)
CVA with giddiness and slurring of speech
0 (0%)
2 (9.09%)
Left upper limb weakness
0 (0%)
1 (4.55%)
Multiple episodes of giddiness
1 (5.26%)
3 (13.64%)
Right stroke with carotid stenosis
2 (10.53%)
0 (0%)
Slurring of speech and imbalance
4 (21.05%)
0 (0%)
Syncopal attack
1 (5.26%)
0 (0%)
TIA
5 (26.32%)
6 (27.27%)
Treated for acute stroke—came after 3 weeks for carotid stenting
0 (0%)
1 (4.55%)
Unsteady gait with impaired vision
2 (10.53%)
0 (0%)
Weakness in upper and lower limbs
2 (10.53%)
4 (18.18%)
Associated findings/complaints (
n
= 6)
Associated stroke
0 (0%)
1 (20%)
Cerebral hyperperfusion syndrome
0 (0%)
1 (20%)
Free floating thrombus in distal CCA extending into ICA
0 (0%)
1 (20%)
Left intracranial stenting also done for petrous and lacerum segments by Xience and
Biomine stents
0 (0%)
1 (20%)
Recanalization by drug-eluting balloon (Lutonix)
For neointimal hyperplasia
1 (100%)
0 (0%)
Abbreviations: CCA, common carotid artery; CVA, cerebrovascular accident; ICA, internal
carotid artery; TIA, transient ischemic attack.
a No statistical test was applied due to 0 subjects in the cells.
In single- and dual-layer stents group, all 100% were with good wall apposition. One
(5.26%) participant in single-layer group had reclusion/restenosis at 30 days. In
single-layer stents group, majority (57.89%; 11 out of 19) showed MRS score of 0 and
31.58% reported MRS score as 1. In dual-layer stents group, majority (63.64%; 14 out
of 22) showed MRS score 0 and 22.73% (5 out of 19) showed score 1 ([Table 3 ]).
Table 3
Comparison of clinical outcomes between study group (n = 41)
Parameter
Study group[a ]
Single-layer stents (n = 19)
Dual-layer stents (n = 22)
Symptomatic Ischemic events
0 (0%)
0 (0%)
Reclusion rate at 30 days
1 (5.26%)
0 (0%)
Good wall apposition
19(100%)
22(100%)
Follow-up MRS score at 30 days
0
11 (57.89%)
14 (63.64%)
1
6 (31.58%)
5 (22.73%)
2
2 (10.53%)
2 (9.09%)
6
0 (0%)
1 (4.55%)
Periprocedural complications
0 (0%)
0 (0%)
Abbreviation: MRS, modified Rankin Scale.
a No statistical test was applied due to 0 subjects in the cells.
Discussion
According to the author's knowledge, this is the first study to compare clinical outcome
and efficacy of single-layer and dual-layer mesh stent for carotid artery stenting
among carotid stenosis patients in Indian scenario. In accordance with our study,
sample size of 41 patients, restenosis in single-layer stenting group, 5.26%, is in
agreement with the results published by Sýkora et al, as 3.4% population of single-layer
stenting had restenosis. However, the same study concluded the restenosis rates are
higher in dual-layer stenting group than in single-layer stenting group.[14 ] The same is contradicted by a meta-analysis published recently by Stabile et al,
which concluded that dual-layer mesh-covered carotid stent systems (the Roadsaver/Casper
or CGuard) can be safely used for CAS and their use minimizes the incremental risk
related to symptomatic status and other risk factors.[15 ] A comparison study conducted by Kahlberg et al reported almost similar results in
both the groups in terms of postprocedural adverse events, namely, TIA/stroke/mortality
with 3% in dual-layer stenting group and 1% in single-layer stenting group.[16 ] This result is in same line with our study results of similar percentage population
in both the groups presented postprocedural adverse events (26.32% in single-layer
stenting group and 27.27% in dual-layer stenting group presented TIA). Lal et al found
several stents used, lesion characteristics (length, ulceration), and procedural related
risk factors of CAS playing a major role in CAS outcomes.[17 ]
However, there is contrast in the opinions that dual-layer stent had a higher rate
of occlusion/restenosis in comparison to single-layer stents[18 ] and dual-layer stents has a lower incidence of embolic events/ restenosis.[19 ] To confirm either of the statement, further studies on large group of population
or larger sample size are required.[20 ] Even the current study has a limitation of smaller sample size.
Findings from this study indicate dual-layer micromesh stent designs minimize embolism
of particle release during stent deployment. For experienced operators attempting
to minimize embolic events with currently available stents, the use of these double-layer
stents is an appropriate strategy to exclude particle extravasation through stent
struts. However, awareness about this approach should be reported and should be cited
as an explanation by any of the interventionists using it.
Limitations
The major limitation is the single-center study with smaller sample size and hence
the results cannot be generalized to overall population. Nonrandomized design and
the potential of selection bias. It was not possible to build multivariable models
to confirm the independent effect of single- and double-layer stents. This study is
not powered for any clinical outcome comparisons, and thus the respective findings
must be treated as hypothesis-generating. Postprocedural antiplatelet medication and
missing follow-up imaging are another limitation. Criteria used by individual practitioners
to choose single-layer and double-layer were unknown. Information on vessel diameter
was not recorded. Other comorbidities associated were not evaluated that could affect
the findings of study. Patients were followed for a period of 1 month only. Despite
the limitations, the study provided real-world cohort data of patients undergoing
CAS. Future multicentric longitudinal studies are recommended to validate the findings
of present study. In asymptomatic carotid stenosis patients, large-scale evidence
for the efficacy of carotid stent systems is highly desirable,
Conclusion
The results of the above study conclude that the both the stents are equally effective.
Even more, both the stents had similar clinical complications and were equally effective
in preventing periprocedural complications. Technical steps should be taken care during
stent placement by avoiding movement of delivery system. This technical proficiency
depends on the stent operator, who also modifies and reduces procedure-related risk
factor during CAS.
