Influence of stenting with open-cell stents vs close-cell stents on the outcomes of patients with bilateral carotid stenosis : Journal of the Chinese Medical Association

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Influence of stenting with open-cell stents vs close-cell stents on the outcomes of patients with bilateral carotid stenosis

Lee, Han-Juia,b; Chang, Feng-Chia,b,*; Luo, Chao-Baoa,b; Guo, Wan-Yuoa,b

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Journal of the Chinese Medical Association 82(1):p 66-71, January 2019. | DOI: 10.1097/JCMA.0000000000000006.
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The efficacy of carotid artery stenting (CAS) is comparable to that of carotid endarterectomy (CEA) for preventing ischemic stroke in patients with severe carotid stenosis, especially elderly patients with severe carotid stenosis; those with comorbidities such as congestive heart failure, unstable angina, and contralateral carotid occlusion; and recipients of prior radiation therapy of the neck.1 Since performance of the first percutaneous carotid angioplasty in 1980,2 several carotid stents varying in configuration and design have become commercially available. These stents provided scaffolding to prop open the artery and prevent it from being occluded by further embolization, though plaque continued to occupy the space between the vessel wall and the stent. Open-cell stent (OCS) and closed-cell stent (CCS) designs defined by the free cell area between stent lattices have been compared using the rates of transient ischemic attack, stroke, or death at 30 days after the procedures and rate of embolic events detected on diffusion-weighted images as measures of efficacy.3–7 However, the results of these trials have not been conclusive.

The rate of in-stent restenosis (ISR) after CAS (reportedly, 3–33%) warrants long-term follow up. Age, prior CEA, irradiation, insufficient stent deployment, and systemic diseases such as dyslipidemia and diabetes mellitus are known risk factors for ISR.8 In two retrospective studies comparing the ISR during a 2-year follow-up of stenting with either OCS or CCS in patients with various clinical risk factors, one revealed no difference in stent patency; the other showed higher ISR and more embolic events after OCS placement than after CCS placement.6,9 These studies evaluated differences due to stent design between the two groups but not the clinical risk factors of each patient.

We hypothesized that differences in genetic makeup and tissue reaction to the different metallic stent designs between individual patients may influence the long-term outcomes of stent deployment.10 The possible influence of these inter-individual differences on the evaluation of OCS and CCS therapy outcomes have not been described before. We designed this retrospective study to compare OCS therapy outcomes with CCS therapy outcomes in a group of bilateral carotid stenosis patients who accepted CAS with OCS in one artery and CCS in the contralateral artery. We aimed to exclude the influence of inter-individual differences from this analysis.


2.1. Patient selection

This single-center, non-randomized, retrospective study was approved by the institutional review board of our hospital and did not require informed consents from the patients.

From 2000 to 2016, stent deployment was carried out simultaneously or in stages in 380 patients with severe bilateral carotid stenosis at our institute by experienced operators (all of whom had more than 10 years of experience). The indications for CAS included symptomatic atherosclerotic stenosis of 60% to 99% and asymptomatic atherosclerotic stenosis of 70% to 99% as determined by the North American Symptomatic Carotid Endarterectomy Trial (NASCET).11 Of the 380 patients, 55 accepted CAS with OCS on one side and CCS on the other. Three patients were excluded because of loss to follow-up. Totally 52 patients were included in this study.

2.2. CAS Procedure

All of the patients received dual anti-platelet therapy 3 days before the procedure. The dual antiplatelet therapy lasted 1–2 months post-procedurally and was followed by aspirin indefinitely.

During the procedure, an angiogram of the supra-aortic arteries and bilateral common carotid arteries (Figs. 1A–D) was followed by placement of a distal embolic protection device (FilterWire EX/EZ, Boston Scientific, Natick, MA, USA) in the distal cervical ICA. We used an OCS (either the Precise® [Cordis, Fremont, CA, USA], Acculink® [Abbott Vascular, Santa Clara, CA, USA], or Protégé® [ev3, Endovascular, Inc., Plymouth, MA, USA]) and a CCS (the Carotid Wallstent® [Boston Scientific]). The selection of the stents was based on the vascular anatomy and lesion morphology.12 Successful revascularization was defined as stenting with less than 30% residual stenosis. After the procedure, the patient was sent to the intensive care unit for observation of at least 24 hours. All technical complications were recorded.

Fig. 1:
An 81-year-old male patient with bilateral symptomatic carotid stenosis of about 90% (left side, long arrow in A; right side, long arrow in B). He underwent a two-stage CAS with deployment of CCS on the left side (C, short arrows) and OCS on the right side (D, short arrows). Serial images of the OCS implantation site at the 3-year (E, MRA) and 4-year follow-up (F, CTA) revealed in-stent restenosis of about 30% with neointimal hyperplasia (E-F, dashed arrow). No ISR was found in the contralateral artery (the site of CCS deployment) at the 3-year (G, MRA), and 4-year follow-up (H, CTA, arrow).

2.3. Clinical evaluation and imaging follow-up

The demographic data and clinical data including cerebrovascular risk factors, clinical comorbidities of coronary artery disease, presence or absence of peripheral arterial occlusive disease, and previous history of radiation therapy of the head and neck cancer were obtained from the medical records of 52 patients (48 males and 4 females). The peri-procedural events (including any cerebral ischemic insult, acute myocardial infarct, or death within 30 days of CAS), any recurrent cerebral ischemic symptoms (including stroke attacks), and death during the long-term follow-up were recorded.

Two neuroradiologists evaluated the images by consensus, including digital subtraction angiography before and after CAS, and diffusion-weighted MR exam within 72 hours of CAS to screen for ischemic spots. Stent patency was established by duplex ultrasound,12 and CTA or MRA was conducted to follow up the residual or recurrent plaque morphology and thrombus burden in spite of interference by metallic artifacts especially of the Cobalt-based alloy stent (Wallstent®)13 (Figs. 1E–H). Catheter angiography remained the gold standard for ISR detection and was reserved for pre-procedural evaluation.

2.4. Statistical analysis

The data are expressed as absolute values, percentages, median, and mean values. The categorical data were compared by the McNemar’s test and Kappa statistics. A p value less than 0.05 was considered significant. SAS (Cary, NC, USA) was used for all calculations.


3.1. Demographics

The demographic characteristics and cerebrovascular risk factors are shown in Table 1. Fifteen patients had a history of cervical radiation therapy (XRT) for head and neck cancers.

Table 1:
Demographic features of the 52 patients with bilateral carotid stenosis who received angioplasty and stenting with open-cell and closed-cell stents

3.2. CAS procedures

Four patients accepted bilateral CAS in a single procedure and 48 patients accepted bilateral CAS in stages: OCS placement preceded CCS placement in 15 patients and succeeded CCS placement in 32 patients, with the interval between the two procedures being 0–99 months, median 4 months.

OCS were deployed in the right and left carotid arteries in 22 (42%) and 30 (58%) patients, respectively, while CCS were deployed in the contralateral carotid artery (p = .27). Symptomatic stenosis was treated by OCS placement in 22 patients and by CCS placement in 29 patients. The follow-up periods were similar after OCS and CCS placement (1–162, median 30 months, vs 2–150, median 38 months, p = .89). The extent of carotid stenosis at the OCS and CCS deployment sites was 79±11 (60–99)% and 81±11 (60–99)%, respectively (p = .81). No tandem lesions were noted. Successful revascularization was achieved in all patients of both groups except for one patient who was left with 40% residual stenosis after CCS placement due to the high risk of hyperperfusion syndrome. Nevertheless, the artery at the lesion site showed less than 30% residual stenosis in the long-term follow up examination.

3.3. Peri-procedural outcomes

The outcomes of all patients and patients with and without XRT are summarized in Tables 2-1, 2-2, and 2–3. None of the patients had symptomatic stroke or acute myocardial infarction or died within the 30-day period after the procedure in both groups. The rate of ischemic spot development on early post-procedural diffusion-weighted imaging (ISDWI) seemed to be higher in the OCS group, but the inter-group difference was not significant (p = .10).

Table 2-1:
Outcome of the 52 patients with bilateral carotid stenosis who received angioplasty and stenting with open-cell and closed-cell stents
Table 2-2:
Outcome of bilateral carotid stenosis in the 15 patients with history of cervical radiation therapy (xrt) who received angioplasty and stenting with open-cell and closed-cell stents
Table 2-3:
Outcome of bilateral carotid stenosis in the 37 patients without history of cervical radiation therapy (xrt) who received angioplasty and stenting with open-cell and closed-cell stents

3.4. Long-term outcomes

Two major cerebrovascular events were found at the sites of OCS placement during follow-up. One was in a 62-year-old male patient who had 95% symptomatic stenosis in the right proximal ICA (which was stented with OCS) and 95% symptomatic stenosis in the left proximal ICA (which was stented with CCS). About 70% ISR was noted on the right OCS side and less than 30% ISR was found on the left CCS side at the five-year follow-up. He had recurrent embolic infarcts and a major stroke on the right OCS side at nine years after the procedure. The other patient was a 64-year-old male patient who had a history of irradiation for nasopharyngeal carcinoma. He had 75% symptomatic stenosis in the left carotid artery and accepted CAS with OCS, and he had about 30% ISR of the OCS at the seven-month follow up. He suffered from ipsilateral major stroke with infarct in the territory of the ipsilateral middle cerebral artery at the post-procedural ninth-month. There were no differences in ISR between the OCS- and CCS-stented arteries in all patients as well as between the XRT and non-XRT groups (p = .71, .39, .80, respectively). In summation for both OCS and CCS, the overall ISR was more than 50% in 20 (19%) CAS patients and less than 50% in 16 (15%) CAS patients. Although 10 (19%) patients died of non-neurovascular causes, none died of neurovascular disease.


In many trials and one meta-analysis, the risk of peri-procedural stroke and death was higher during CAS than during CEA.14,15 Recent technical improvements in CAS have reduced CAS-associated risk so that now it is comparable with CEA-associated risk.16 The design of the stent itself (not the cerebral embolic protection devices) plays an important role in the outcomes of CAS.3 The risk of embolic events after CAS may be related to clinically silent ischemic lesions on diffusion-weighted MR images. While being conformable and tractable, ideal carotid stents must have sufficient radial force to prevent stent collapse, and be durable enough to prevent fracture. The open cell stent (OCS) with large free cell area can navigate more tortuous and serpentine vessels and will resist shortening unnecessarily due to its high flexibility. On the other hand, the more tightly woven closed cell stent (CCS) with smaller free cell area is stiffer and provides better scaffold support in plaque-burdened areas of the artery. The outcomes of stent deployment are influenced by three stent design factors: radial force, size of free-surface area, and scaffold support.17,18

Theoretically, the smaller free cell area of the CCS should

produce better outcomes with respect to post-procedural embolic events and ISR. CCS placement was associated with improved outcomes in symptomatic patients in two large retrospective studies.4,19 The use of large-free-cell-area stents in combination with embolic protection devices has been proposed to reduce the clinical impact of the large embolic particles, escaping these stents, on periprocedural outcomes.5 Our results revealed a tendency toward higher ISDWI rate in the OCS group with no significant difference. These results may be related to a trend toward higher risk of embolic events in the OCS group, or to a type 2 statistical error given the small sample size. The use of distal cerebral protection devices in our study as well as previous studies6 may account for the absence of between-group differences in post-procedural events. One study comparing patients with a history of cervical radiation therapy (XRT) (vs patients with no history) reported no increased morbidity in the former despite the larger size of the embolic particles captured by their protection devices.20 In our study of XRT patients, the rates of embolic events and ISDWI were similar between the CCS and OCS groups. However, the ISDWI rate tended to be higher in the OCS group. A randomized prospective study with a larger sample size is needed for comparing CAS with CCS and OCS, especially in XRT patients.

Four major factors affect the role that in-stent restenosis (ISR) plays in long-term safety and efficacy in CAS. These include the lesion, stent design and materials, the patient, and genetic factors.21,22 The three phases of ISR are early endothelial injury, granulation tissue formation, and tissue remodeling. The smooth muscle cells are key elements of neointimal formation and progression to restenosis.10,23,24 The rate of ISR was reported to be higher after CAS than after CEA in previous studies,25,26 and similar in CAS with OCS vs CCS despite differences in clinical risk factors.6 Our study found similar ISR rates regardless of stent design in the same patients (i.e., under uniform conditions of pathophysiologic shear and genetic background). However, major recurrent stroke events occurred in 2 out of 52 patients with 104 treated carotid re-stenoses after CAS; both occurred on the OCS side, with one implant associated with severe ISR five years later. These findings suggest that patients with severe carotid stenosis who accept CAS with OCS deserve close and long-term post-procedural follow-up. Nevertheless, we concluded that both OCS and CCS are reliable designs for CAS in patients with severe carotid stenosis.

The extent of post-radiation carotid stenosis depends on the area of the previously irradiated region, which may possibly involve long segments of the internal and common carotid arteries. The exact pathogenesis is still unclear, but endothelium dysfunction, extensive fibrosis of the arterial wall, intimal proliferation, injury and occlusion of the vasa vasorum as well as accelerated atherosclerosis may all contribute to carotid stenosis.27 Moreover, increased rate of ISR in CAS patients after XRT has been widely reported. A large meta-analysis of 533 patients with carotid stenosis after XRT compared CEA with CAS and revealed higher rate of ISR > 50% (ranging from 12% to 42%) and occlusion after CAS, although in most cases, ISR remained benign and asymptomatic.28 The stent margin restenosis in our cases may be related to CCS shortening and inadequate OCS length (maximum, 4 cm). We suggest determining the length of carotid stenosis in the previously irradiated field before deciding the number of stents to implant. We also suggest close follow-up of these irradiated patients for early detection of instent and stent margin restenosis.

Limitations of our study were due to its design (i.e., a single-center, non-randomized, retrospective study), which is prone to bias from selecting stents according to vascular anatomy and lesion morphology. Stent selection on this basis might bias the outcome. Second, the study size, and therefore the number of events and outcomes, was too small to demonstrate a difference between the stent designs. Third, the intra-individual variability in the interval between placement of the two types of stents as well as the long study enrollment period resulted in variation in the design of the deployed stents. Fourth, the ISD- WI may have been caused by plaque emboli after stent deployment or by the angiographic procedure during CAS. Moreover, radiation dosage to the bilateral neck region varied depending on the previous tumor type and staging. One side may have received a larger irradiation dose, thus affecting the comparison of post-procedural events including bilateral carotid artery ISR. A larger, randomized prospective study is needed in the future.

In conclusion, CAS with both OCS and CCS had no significant effect on short-term outcomes and long-term outcomes in patients with severe carotid stenosis. The study does not support the superiority of a specific carotid stent cell design as assessed by the rates of periprocedural cerebral ischemic insult, long-term stent patency, and stroke recurrence. We suggest both OCS and CCS are feasible CAS options for treating patients with severe carotid stenosis.


This research was co-sponsored by Taipei Veterans General Hospital (grant number: V106C-197) and Ministry of Science and Technology (grant number: 105-2314-B-075-027-MY2). We also thank Dr. Z. Sean Juo for English editing of this manuscript.


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Atherosclerosis; Carotid stenosis; Carotid stent; Stroke

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