2003, Cremonesi et al. published a series of 442 consecutive patients treated with carotid stent implantation with embolic protection. Stroke or death within the first month after the procedure occurred in 1.1% of these patients (Cremonesi et al. 2003).
Biasi et al. reported on the use of the echogenicity index, known as the gray scale median, as an indicator of the risk of stroke during carotid stent implantation. The authors concluded that low echogenicity in the carotid plaque, measured as a gray scale median ≤ 25, increased the risk of peri-interventional stroke (Biasi et al. 2004). The German Association for Angiology and Radiology has developed a prospective registry for carotid stent implantations. The results for the first 48 months, from a total of 38 participating centers, were published in 2004. Carotid stent implantation was carried out in 3267 patients. The procedure was successful in 98% of the interventions. The peri-interventional mortality was 0.6%, the major stroke rate was 1.2%, and the minor stroke rate was 1.3% (Theiss et al. 2004).
In 2005, Bosiers et al. published the ELOCAS Registry, compiled retrospectively and prospectively from the results of four “highvolume centers.” A total of 2172 consecutive patients were treated, and 99.7% of the procedures were technically successful. The stroke/death rate was 4.1% after 1 year, 10.1% after 3 years, and 15.5% after 5 years (Bosiers et al. 2005).
The CaRESS study was a nonrandomized multicenter study including 143 patients treated with carotid stent implantation and 254 patients who underwent carotid endarterectomy. No significant differences were observed with regard to the stroke/death rates either after 30 days (2.1% stent, 3.6% surgery) or after 1 year (10.0% stent, 13.6% surgery) (CaRESS 2005).
The ARCHeR study was published by Gray et al. in 2006 and consisted of three sequential multicenter studies. In ARCHeR 1, only the use of the Acculink (Guidant) carotid stent was evaluated; in the two subsequent studies (ARCHeR 2 and 3), adjuvant use of the Accunet embolic protection system (Guidant) was also tested. A total of 581 patients with high surgical risk from 48 centers were included between 2000 and 2003. The combined stroke/death/myocardial infarction rate was 8.3% after 30 days. The ipsilateral stroke rate after the first month and up to 1 year was 1.8%. The repeat stenosis rate was 2.2% within the first year (Gray et al. 2006).
The CAPTURE Registry (Carotid Acculink/Accunet Post-Approval Trial to Uncover Unanticipated or Rare Events) was published in 2007. A total of 3500 patients with high surgical risk and a stenosis grade > 50% (symptomatic) or > 80% (asymptomatic) were included. The stroke/death/myocardial infarction rate was 6.3% after 30 days. The major stroke/death rate after 30 days was 2.9%.
Embolism protection systems have been evaluated in several large, unrandomized multicenter studies. These include the European DESERVE study (Diffusion-Weighted MRI-Based Evaluation of the Effectiveness of the Mo.Ma System), which demonstrated that the Mo.Ma system, using diffusion-weighted magnetic resonance imaging (DW-MRI) during carotid stent implantation, is effective for protection against embolism. The cranial MRI examination was carried out before the procedure and 3–12 hours after carotid stent implantation in order to identify new ischemic lesions. In a total of 127 patients treated, new cerebral lesions were identified on DWMRI in 38 (29.9%). However, clinically relevant stroke was only present in three patients (2.4%) (Rubino et al., paper presented at EuroPCR 2011).
In the EMPIRE Study, the Gore Flow Reversal System was evaluated in 29 centers with a total of 245 patients. The primary end point was the rate of myocardial infarction/stroke/death after 30 days. Thirty-two percent of the patients were treated for symptomatic carotid stenosis. Intolerance for balloon occlusion was noted in a total of six patients in the study (2.4%). The primary end point occurred in 3.7% of the patients (Clair et al 2011).
In the EMBOLDEN Study, the Gore Embolic Filter was evaluated in a total of 250 patients in 35 centers in 2009–2010. Fifteen percent of the patients included in the study were suffering from symptomatic carotid stenosis. After 30 days, 10 patients (4.0%) reached the primary end point, defined as myocardial infarction, stroke, and/or death (Gray et al., paper presented at the 23rd Annual International Symposium on Endovascular Therapy, 2011).
Randomized studies on carotid stent implantation
The Carotid and Vertebral Transluminal Angioplasty Study (CAVA-TAS I) was the first large-scale study in which carotid angioplasty (largely without stenting and embolic protection) was compared with carotid endarterectomy. The early stroke/death rate was 10% in both the carotid angioplasty and carotid endarterectomy groups. In the SAPPHIRE Study, carotid stent implantation using embolic protection was compared with carotid endarterectomy both in a randomized study and in a registry. The 30-day stroke/death rate was 4.5% in the group with randomized carotid stent implantations and 6.6% in the group of randomized patients who underwent surgical treatment. The registry also included patients who did not meet the inclusion criteria for the randomized study. The 30-day stroke/death rate in the registry among patients who underwent interventional treatment was 6.9%.
The EVA-3S study compared carotid stent implantation with carotid endarterectomy in patients with symptomatic stenoses ≥ 60%. The participation criteria for interventionalists were set very low; a participating interventionalist only had to have implanted 12 carotid stents beforehand. The stroke/death rate after 30 days was lower in the group of patients treated with embolic protection than in the group without embolic protection (18 of 227, 7.9% versus 5 of 20, 25%; P = 0.03). Randomization to the group with stent implantation without embolic protection was therefore prematurely stopped. The stroke/death rate after 30 days in the group with stent implantations with embolic protection was significantly higher (9.6%) in comparison with endarterectomy (3.9%). The relative risk was 2.5.
The SPACE (Stent-Protected Percutaneous Angioplasty of the Carotid versus Endarterectomy) study included patients with symptomatic stenoses ≥ 70% on duplex ultrasonography or ≥ 50% according to the NASCET criteria. The use of embolic protection systems was optional in this study. Many interventional centers had difficulties in meeting the participation criteria—at least 25 carotid stent implantations had to have been carried out previously. The 30-day ipsilateral stroke rate was 6.84% in the group of patients treated with carotid stent implantation, and in the surgical group, the rate was 6.34%. Although using embolic protection systems had already become a standard part of the procedure in most centers, 73% of the interventions in this study were carried out without embolic protection. Complications such as myocardial infarction, contralateral stroke, and cranial nerve lesions, which are almost exclusively complications of endarterectomy, were not evaluated. The study was designed as a non-inferiority study with a non-inferiority margin of < 2.5% which was based on a calculated complication rate of 5%. The one-sided P value for non-inferiority was 0.09. The study was terminated prematurely after inclusion of 1200 patients due to low patient recruitment and lack of finance when an analysis determined that including more than 2500 patients would have been necessary to reach a statistical power of at least 80%. According to the investigating physicians in the study, the study results were not capable of definitively demonstrating the non-inferiority of carotid stent implantation in comparison with carotid endarterectomy since the trial was not completed.
Overall, the results of the large randomized studies indicate that the differences between surgery and intervention were usually very small.
The Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST) study started recruiting patients in 2000. Preliminary data from the introductory
