Benefits and pitfalls of carotid stents with dual-layer design - a systematic review

Overview

Aim: Carotid artery stenting is considered an important minimally invasive treatment modality in stenotic carotid artery disease. First-generation carotid stents have been associated with a higher rate of neurologic complications than carotid endarterectomy. To minimize atherosclerotic plaque prolapses and subsequent embolization, a second generation of micromesh-covered stents has been developed. The aim of this systematic review is to describe the main advantages and possible limitations of carotid stents with dual-layer design. Methods: The articles were selected in accordance with the PRISMA guidelines. The databases Scopus, PubMed and Web of Science were searched, 247 publications were selected for analysis, and 128 duplicates were removed. Based on the exclusion criteria, 81 publications were omitted. The reference lists of the 38 remaining articles were reviewed and six additional relevant sources were found. A total of 44 publications were included in the review. Results: Studies show that the use of dual-layer stents reduces the incidence of periprocedural cerebral embolism and the incidence of ipsilateral stroke at 30 days and 12 months both in asymptomatic and symptomatic patients. However, second generation stents show fundamental differences in stent construction and also in their clinical outcomes. Conclusion: The dual-layer stent technology may improve short- and long-term clinical results of carotid artery stenting. Although randomized trials comparing second-generation stents with surgical treatment are lacking, currently published results may significantly influence decision-making in primary and secondary stroke prevention.

Keywords:

dual-layer stent – carotid artery stenting – carotid artery stenosis

This is an unauthorised machine translation into English made using the DeepL Translate Pro translator. The editors do not guarantee that the content of the article corresponds fully to the original language version.

 

Introduction

Carotid artery stenting (carotid artery stenting; CAS) has become an important minimally invasive treatment option for carotid artery stenosis alongside carotid endarterectomy (CEA) as part of primary and secondary prevention of stroke. However, according to a meta-analysis of large randomized trials, CAS is associated with a higher incidence of ipsilateral stroke than CEA [1]. A significant proportion of these events (30-60%) occur in the postprocedural period and in many cases are attributed to prolapse of the atherosclerotic plaque through the stent mesh with subsequent   embolization [2].

Minimizing plaque rupture has become one of the major challenges in the endovascular treatment of carotid stenosis. In order to reduce the incidence of neurological events in CAS, a new type of micro-mesh covered stents, also referred to as second-generation stents, has been developed. This design allows effective overlap of the plaque and thus forms a mechanical barrier reducing the embologenic potential of the plaque [2,3].

Several studies [4-10], including two randomized trials [11,12], show that double-layer stents can improve CAS outcomes by minimizing the incidence of peri- and postprocedural stroke.

The aim of this article is to systematically review the outcomes of CAS with double layer stents, the incidence of peri- and postprocedural stroke, the incidence of restenosis, and the results of the use of second-generation stents in the emergent treatment of carotid stenosis in the treatment of stroke with tandem lesions. We also aimed to compare the outcomes of different types of double-layer stents.

 

Methods

Publications were searched in Scopus, PubMed and Web of Science databases using the terms "carotid artery" AND "stent" in combination with the terms "double layer" OR "double mesh" OR "dual mesh" OR "dual layer". Inclusion criteria for inclusion in the analysis were: peer-reviewed publications, human studies, English/Czech/Slovak language. Exclusion criteria were: non-relevant publications, studies with less than 15 patients, case studies and commentaries. A total of 247 publications were found based on the initial search. After removing 128 duplicates, 119 articles were selected for further analysis. Based on the exclusion criteria, 81 publications were removed.

After reviewi;ng the reference lists of the remaining 38 studies, a further 6 relevant sources were traced. A total of 44 publications meeting the PRISMA recommendation criteria [13] were included in the review, including five meta-analyses and one systematic review. A flowchart of the selection of publications is shown in Fig. 1.

 

Types of stents

Currently, three types of double-layer carotid stents are available. They differ in the material and design of the micro-mesh as well as its positioning relative to the stent.

    Roadsaver®  Carotid artery stent system (Terumo, Tokyo, Japan) and Casper Rx^TM (Microvention, Tustin, CA, USA). These are the same device with two different names. The self-expandable closed-cell stent has a nitinol micro-mesh placed on the inside of the stent with a pore diameter of 375-500 μm (Figure 2). Up to 50% of the stent length is open, the stent can be withdrawn into the deployment system and repositioning can be performed if necessary. The outer diameter of the deployment system is 5F [14].

    CGuard^TM (InspireMD Inc., Boston, MA, USA). The nitinol self-expandable open-cell stent construct is covered on the outside with a patented MicroNet mesh of 20 μm thick polyethylene terephthalate fiber with 150-180 μm pore size (Figure 3). The outer diameter of the deployment system is 6F [14].

    GORE® Carotid Stent (W.L. Gore & Associates, Inc., Flagstaff, AZ, USA). The self-expandable open-cell nitinovolume stent is externally covered with a perforated polytetrafluoroethylene/Teflon membrane with a pore size of 500 μm. A CBAS® Heparin Surface heparin film is bonded to the stent surface to form a persistent antithrombogenic surface. The deployment system is 5F or 6F [15].

 

Peri- and postprocedural stroke

The main limitation of CAS with first-generation stents is the higher incidence of peri- and postprocedural stroke compared with CEA [16,17]. A recent randomized trial showed a significant reduction in the incidence of new lesions on diffusion-weighted MR images, a marker of periprocedural embolization, with micro-mesh covered stents compared with first-generation stents [12]. Another randomized trial demonstrated by transcranial Doppler the lowest incidence of myco-embolic signals when using the Roadsaver stent and proximal balloon  embolization [11].

In 2022, several meta-analyses have been published showing encouraging results for double-layer stents, but larger prospective studies comparing conventional and double-layer stents have not yet been published. According to a meta-analysis by Pini et al [14] including 14 studies and 1955 patients, the 30-day incidence of stroke is 1.4%. Asymptomatic patients had an incidence of STROKE of 1.5%, a significant shift compared to the recent randomized Second Asymptomatic Carotid Surgery Trial (ACST-2), where the incidence of STROKE was 3.6% [18].

Very good results were also achieved in symptomatic patients with a 30-day incidence of stroke of 1.9% [14]. In symptomatic patients, a significantly higher incidence of stroke has been previously published, up to 7% in the randomized International Carotid Stenting Study (ICSS) [19].

There is accumulating data that differences in the design of double-layer stents affect the clinical outcomes of CAS. Comparison of individual double-layer stents revealed significant differences between them. According to data from a meta-analysis, the 30-day incidence of stroke with the Casper/ Roadsaver stent is 0.5% and 0.54% with the CGuard stent. However, it is 2.89% with the Gore stent. The 12-month incidence of ipsilateral STROKE with the Gore stent is 3.1%, which is also significantly higher than the 0.26% with the Casper/ Roadsaver stent and 0.38% with the CGuard stent. Compared with first-generation stents, the Casper/ Roadsaver and CGuard stents reduce both 30-day and 12-month STROKE incidence. No significant differences were demonstrated with the Gore stent compared to conventional stents [2]. A review of the literature reporting the periprocedural incidence of STROKE with double-layer carotid stents is summarized in Table 1.

More detailed data are awaited from the ongoing ROADSAVER study conducted on 1967 patients. Preliminary results suggest that the 30-day incidence of stroke is low with (2%) and without (1.3%) periprocedural emboloprotection [35].

 

Restenosis

Individual double-layer stents also differ in the incidence of restenosis. According to the data from the meta-analysis, the annual incidence of in-stent restenosis in first-generation stents is 3.97% and does not differ significantly from the 4.83% incidence of in-stent restenosis in the Gore stent. While restenoses are significantly less frequent with the CGuard stent (0.34%), they are observed significantly more frequently with the Casper/ Rodsaver stent (7.16%) [2]. An increased incidence of restenosis in this type of stent has also been described by other authors [27].

A significantly higher annual incidence of Casper stent restenosis (8.2%) compared to first-generation stents (1.7%) was also observed in our patients. At a median follow-up of 24 months, restenosis rates increased to 13.3% with Casper [36]. A review of the literature reporting the incidence of restenosis and the need for reintervention in second-generation carotid stents is summarized in Table 2.

According to the 2017 European Society for Vascular Surgery (ESVS) recommendations, reintervention is indicated only in symptomatic restenosis [41], therefore the clinical impact of predominantly asymptomatic restenosis remains unclear.

After covering the arteria carotis externa (ACE) with a double-layer stent, the 30-day incidence of its occlusion is described as 0-1.9% [23,30,32]. In a large study with 726 patients, ACE patency was 98.8% at 1-year follow-up [40].

 

Ultrasound checks

The Casper stent should be evaluated with caution during ultrasound examination because this stent appears to cause an increase in peak systolic velocity (PSV) even in the absence of other signs of restenosis. Mutzenbach et al describe that 22.2% of these stents showed increased PSV at 100-199 , with normal B-mode and color Doppler imaging [39]. The effect on PSV was also observed in our patients treated with this stent. An increase in PSV to 130-299 was found in 12% of cases during follow-up [36].

To assess the severity of Casper stent restenosis, values of 200 cm/s for moderate and 300 for severe in-stent restenosis have been proposed [39].

Due to the double-layered structure of the Casper stent with more metallic material, consistent periprocedural antiplatelet therapy is important and platelet function testing is also advisable. Slightly longer dual antiplatelet therapy after the procedure is also recommended [27].

 

Stenting in acute STROKE

Although a 30-day occlusion rate of 0.8% has been described for double-layer stents in elective procedures [14], which is comparable to the 0.6% incidence of acute thrombosis with standard carotid stents [42], a higher incidence of early occlusion has been described for double-layer metallic micro-mesh stents used acutely to treat carotid stenosis as part of emergent treatment for sudden stroke [43,44].

Köcher et al describe a significantly higher incidence of early closure of double layer stents (26.6%) compared to conventional stents. However, no significant difference in patient functional status at three months was demonstrated [45].

Although a multicentre study did not confirm a higher incidence of occlusions or an impact on the neurological status of the patient [46], the authors recommend stricter adherence to antiplatelet therapy and longer angiographic follow-up after implantation as prevention of thrombus formation and occlusion when using this type of stent in the treatment of tandem occlusions. The higher thrombogenicity of double-layer stents in patients without prior dual antiplatelet therapy is thought to be due to the greater amount of metallic material. Another factor that may contribute to more frequent in-stent thrombosis is the delayed restoration of blood flow in patients with tandem intracranial occlusion, especially if the extracranial lesion is stented first. A review of the literature reporting the incidence of early closure of double-layer stents in the treatment of acute stroke is summarized in Table 3. Early use of antiplatelet therapy, including GP IIb/IIIa receptor inhibitors, appears to be warranted in the prevention of early stent closure [51,53-55]. Initial data on the use of the CGuard stent in acute CAS describe a low incidence of both in-stent thrombosis and stent occlusion [52].

 

Conclusion

The carotid stent, together with antiplatelet therapy, plays a major defensive role against postprocedural embolic complications from the newly remodeled atherosclerotic plaque. The use of double-layer carotid stents appears to be associated with better short- and long-term clinical outcomes of CAS, reducing the incidence of periprocedural cerebral embolization, 30-day and 12-month incidence of ipsilateral stroke in both asymptomatic and symptomatic patients.

Future randomized trials comparing second-generation stents with current surgical outcomes and with hybrid techniques of transcarotid arterial revascularization are needed. There is also a need to evaluate the long-term outcomes of the use of double-layer stents. However, the results already published today may already significantly influence decision making in clinical practice in primary and secondary prevention of stroke with carotid stenting.

 

Grant support

This work was supported by Operational Program Integrated Infrastructure for the project: TENSION - complementary project, IMTS: 313011W875, co-financed by the European Regional Development Fund.

 

Conflict of interest

The authors declare that they have no potential conflict of interest.

 

Tables

Table 1: Literature review reporting peri- and postprocedural incidence of stroke in carotid artery stenting with double-layer carotid stents.

	Number of patients	Stent	CMP within 30 days	Stent occlusion	Age	Men
Bosiers et al 2016 [20]	100	Roadsaver/Casper	1 %	0 %	73	70 %
Casana et al 2017 [21]	82	CGuard	1,2 %	1,2 %	74	75 %
Mutzenbach et al 2018 [22]	138	Roadsaver/Casper	0 %	0 %	71	76 %
Nerla et al 2018 [23]	150	Roadsaver/Casper	0 %	0 %	74	75 %
Speziale et al 2018 [24]	200	CGuard	2,5 %	0 %	73	66 %
Gray et al 2019 [15]	264	GORE Carotid Stent	1,1 %		73	64 %
Ruffino et al 2019 [25]	50	Roadsaver and CGuard	0 %	0 %	74	66 %
Wissgott et al 2019 [26]	30	CGuard	0 %	0 %	72	87 %
Imamura et al 2020 [27]	140	Roadsaver/Casper	1,4 %	0 %	73	88 %
Machnik et al 2020 [28]	298	Roadsaver/Casper	3 %	0,7 %	71	71 %
Mazurek et al 2020 [29]	106	CGuard	0,9 %	0 %	69	70 %
Montorsi et al 2020 [11]	54	Roadsaver/Casper	0,9 %	0 %	71	80 %
Sirignano et al 2020 [30]	733	CGuard	0,5 %	0 %	73	70 %
Kahlberg et al 2021 [31]	100	Roadsaver/Casper	1 %	0 %	73	72 %
Karpenko et al 2021 [12]	50	CGuard	0 %	0 %	65	76 %
Tigkiropoulos et al 2021 [32]	103	CGuard	0 %	0 %	69	87 %
Haas et al 2022 [33]	116	Roadsaver/Casper	0 %	0 %	73	61 %
Petkoska et al 2022 [34]	105	Roadsaver/Casper	0 %	0 %	68	70 %

 

 

Table 2. Review of the literature reporting the incidence of restenosis and the need for reinterventions in carotid artery stenting with double-layer carotid stents.

	Tracking time (months)	Number of patients	Restaurant	Reintervention	Stent
Bosiers et al 2018 [37]	12	100	7,5 %	2,1 %	Roadsaver/Casper
Capoccia et al 2018 [38]	12	200	1 %	1 %	CGuard
Nerla et al 2018 [23]	12	150	5 %	3 %	Roadsaver/Casper
Gray et al 2019 [15]	12	244	1,2 %	4,1 %	GORE Carotid Stent
Imamura et al 2020 [27]	12	140	8,5 %	2,4 %	Roadsaver/Casper
Machnik et al 2020 [28]	48 max.	298	2,3 %	2,3 %	Roadsaver/Casper
Mazurek et al 2020 [29]	12	106	0,9 %	0,9 %	CGuard
Mutzenbach et al 2020 [39]	12	108	1,9 %	0,9 %	Roadsaver/Casper
Sirignano et al 2021 [40]	12	726	0,82 %	0,28 %	CGuard
Kahlberg et al 2021 [31]	22,3 ± 13,9	100	5 %	1 %	Roadsaver/Casper
Sykora et al 2022 [36]	24 median	83	13,3 %	6 %	Roadsaver/Casper

 

 

Table 3. Literature review reporting the incidence of early stent closure in carotid artery stenting in the treatment of acute stroke with double-layer carotid stents.

	Number of patients	Stent	Early cap	Non-occlusive in-stent thrombosis	Neurological deterioration
Yilmaz et al 2017 [43]	20	Casper	45 %	50 %	0 %
Bartolini et al 2019 [47]	21	Casper	0 %	52,4 %
De Vries et al 2019 [44]	27	Roadsaver and CGuard	18,5 %		11 %
Köcher et al 2019 [45]	15	Casper	26,6 %
Lamanna et al 2019 [48]	19	Casper	10,5 %		5,3 %
Pfaff et al 2019 [46]	160	Casper	7,5 %	20,8 %
Ozpeynirci et al 2020 [49]	28	Casper	3,4 %
Foo et al 2021 [50]	94	Casper	6,4 %		5,3 %
Runck et al 2021 [51]	66	Casper	7,6 %	16,7 %
Klail et al 2022 [52]	33	CGuard	3 %	9 %	3 %