Author + information
- aDivision of Cardiology; Klinikum Neuperlach, Städtisches Klinikum München, Munich, Germany
- bDivision of Cardiology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
- ↵∗Address for correspondence:
Dr. Harald Mudra, Division of Cardiology, Klinikum Neuperlach, Städtisches Klinikum München, Munich, Germany.
For many years, there has been an intensive debate regarding the optimal revascularization technique in patients with carotid artery stenosis, due to conflicting results in the large randomized trials assessing carotid artery stenting (CAS) against carotid endarterectomy (CEA). Unfortunately, the European studies EVA-3S (Endarterectomy Versus Angioplasty in Patients With Severe Symptomatic Carotid Stenosis) (1), SPACE (Stent-Protected Angioplasty Versus Carotid Endarterectomy) (2), and ICSS (International Carotid Stenting Study) (3) have several limitations such as lack of operator experience, inconsistent use of embolic protection devices, and underuse of dual antithrombotic therapy after CAS. The American studies CREST (Carotid Revascularization Endarterectomy Versus Stenting Trial) (4) and ACT-1 (Asymptomatic Carotid Trial) (5), however, used run-in phases for study qualification, mandatory embolic protection, and strict endpoint adjudication. Both studies could demonstrate comparable results with respect to the primary composite endpoint (all-cause death, major or minor stroke, and myocardial infarction) and no significant differences also in major stroke. But even these trials revealed periprocedural minor strokes, albeit lower, but still about 2-fold higher in percutaneously treated patients.
Besides patient selection, stent design is one of the key factors to improve procedural results of CAS because part of the issue of acute and subacute strokes after interventional treatment is the risk of cerebral particle embolization possibly originating from the carotid plaque, which is still in place and only covered by the stent (6). Closed-cell stents may provide more adequate plaque coverage due to a smaller free-cell area (1.1 to 4.4 mm2) and were shown to be associated with smaller particle embolization and reduced risk for stroke after CAS compared with open-cell stents (free-cell area 6.0 to 11.5 mm2) (7). However, they are characterized by poorer flexibility resulting in a higher risk of malapposition as indicated by optical coherence tomography analysis (8). Further reduction in free-cell area with maintenance of stent flexibility can be achieved by mesh-covered stents. Therefore, clinical outcome data of this novel technical feature are of great interest.
In this issue of JACC: Cardiovascular Interventions, 2 trials assessing the presently available mesh-covered carotid stents are presented. The first report by Schneider et al. (9) shows the results of the SCAFFOLD (GORE® Carotid Stent Clinical Study for the Treatment of Carotid Artery Stenosis in Patients at Increased Risk for Adverse Events From Carotid Endarterectomy) trial, a prospective, multicenter, single-arm clinical study evaluating the first-in-man multicentric use of the GORE Carotid Stent (W.L. Gore & Associates, Flagstaff, Arizona) with a 500-μm2 pore size micro-mesh on the exterior of the stent frame. A total of 312 patients were enrolled at 30 sites in the United States. Due to violation of in- and exclusion criteria in 47 patients, 265 patients were analyzed in a so-called per-protocol (PP) analysis and the total cohort of 312 patients in an intention-to-treat (ITT) analysis. Symptomatic carotid stenosis was present in 15%, and the population was characterized by high comorbidity. Anatomic high-risk criteria for CEA (surgically inaccessible lesions, radical head/neck surgery or radiotherapy, spinal immobility of the neck, or restenosis after prior CEA) were present in 43% of the patients. An embolic protection device (distal filter) was used in 94.6% of the cases. The primary endpoint of 30-day death, stroke, or myocardial infarction was 4.8% in the ITT analysis and 3.0% in the PP analysis. The strength of the analysis is the real-world character of the study population including those with high comorbidity (e.g., older patients and more diabetes mellitus than in the randomized trials) and high risk for surgical treatment. Furthermore, the markedly higher stroke rate in the ITT analysis (2.9% compared with 1.1% in the PP analysis) including anatomic high-risk features for CAS such as tortuous vessel anatomy and severe lesion calcification underlines that patient selection is of great importance to achieve high procedural safety. The study shows that consequent use of a protection device, appropriate patient selection, and implantation of novel mesh-covered stents can reduce the 30-day stroke rate down to 1.1%, which is lower than both the CAS and CEA groups in the large randomized trials despite higher patient comorbidity. However, the long-term outcome of the GORE carotid stent has yet to be analyzed.
In the second analysis, Stabile et al. (10) performed a PubMed/Embase search of the published reports on mesh-covered stents in carotid artery treatment. The authors chose 4 trials of >100 patients each for a patient-level meta-analysis. They assessed the 2 dual-layered mesh-covered stent models Roadsaver™ (Terumo Corp, Tokyo, Japan) and CGuard™ (InspireMD, Boston, Massachusetts). The pore size of an inner mesh is about 400 μm2 in the Roadsaver and about 180 μm2 for an outer mesh in the CGuard, respectively. A total of 556 patients were available for analysis with Roadsaver and CGuard stent implantation in similar proportions. The patient characteristics were similar to the SCAFFOLD trial with a slightly higher rate of symptomatic stenosis in 17.3% of the patients. Despite a lower rate of embolic protection device use (92.4%), the 30-day composite of stroke or death occurred in only 1.4% of the patients. Only 1 patient experienced a minor stroke after hospital discharge. Unfortunately, the rate of myocardial infarctions was not reported. Neurological assessment by an independent individual was described in all 4 trials. However, an independent clinical event committee is missing, and correct interpretation and reporting of neurological events is absolutely crucial in trials assessing carotid procedures.
Up to now, there is no evidence for a higher rate of stent thrombosis with mesh-covered stents, but a note of caution remains with respect to a potential higher restenosis rate. Due to their small pore sizes, treatment of unstable plaques in high-risk lesions is a potential target for this stent type, widening the indication for carotid stenting. Ultimately, large randomized trials with longer follow-up comparing mesh-covered stents with CEA and/or conventional stents are urgently needed. If such trials can confirm the results of the current studies, this novel stent technology will really represent a new milestone in CAS.
↵∗ Editorials published in JACC: Cardiovascular Interventions reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Interventions or the American College of Cardiology.
Both authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- 2018 American College of Cardiology Foundation
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