The authors have declared that no competing interests exist.
Conceived and designed the experiments: GG BT GE. Performed the experiments: GG AS. Analyzed the data: GG AS. Wrote the paper: GG ES CP. Creitical review of the manuscript and final approvation: BT GE.
Carotid endarterectomy (CEA) or stenting (CAS) are associated with a relatively low rate of clinical events, but diffusion-weighted imaging (DWI) is increasingly being used to compare the incidence of new ischemic lesions. Therefore, we conducted an updated meta-analysis on the occurrence of post-procedural new DWI lesions after CAS versus CEA.
MEDLINE, Cochrane, ISI Web of Science and SCOPUS databases were searched and 20 studies (2 randomized and 18 non-randomized) with a total of 2104 procedures (CAS = 989; CEA = 1115) were included. The incidence of new DWI cerebral lesions was significantly greater after CAS than CEA (40.3% vs 12.2%; 20 studies; 2104 patients; odds ratio [OR] 5.17; 95% confidence interval [CI], 3.31-8.06; p<0.00001). Also peri-procedural stroke (17 studies; 1833 patients; OR 2.01; 95% CI, 1.14-3.55; p=0.02) and stroke or TIA (17 studies; 1833 patients; OR 2.40; 95% CI, 1.42-4.08; p=0.001) were significantly increased after CAS. This latter clinical advantage in the CEA group over CAS was tempered when CEA procedures were performed with shunting in all instead of selective shunting or when CAS was performed with only closed cell stents instead of both closed and open cell stents, however, no significant differences between subgroups emerged.
CAS is associated with an increased incidence of post-procedural brain DWI lesions. This greater amount of ischemic burden may also reflect a higher rate of cerebral events after CAS. However, whether recent technical advances mainly for CAS could potentially reduce these ischemic events still remains to be evaluated.
Carotid artery revascularization in patients with carotid artery disease has the aim of preventing stroke. Carotid endarterectomy (CEA) is the standard treatment for severe asymptomatic and symptomatic carotid stenoses, but in the last years carotid artery stenting (CAS) has increasingly emerged as minimally invasive alternative to surgery [
The aim of this meta-analysis is to provide updated evidence on the incidence of new brain lesions after CAS compared with CEA as detected by DWI.
The study was designed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) requirements (
Studies included in the meta-analysis.
Studies were included if both criteria were respected: 1) presence of comparison between CAS versus CEA; 2) presence of post-operative incidence of cerebral lesions detected by DWI-MRI in both groups. Exclusion criteria were: 1) duplicate publication; 2) the outcome of interest was not clearly reported or could not be derived from the published results.
Two reviewers independently screened the articles for eligibility. The reviewers compared the selected studies and any discrepancy was resolved by consensus. The number of events of new brain lesions at DWI-MRI, stroke and stroke or transient ischemic attack (TIA), number of participants and the main clinical and procedural characteristics were extracted from each study.
The primary endpoint was the incidence of new brain lesions after CEA or CAS. Secondary endpoints of interest were stroke and stroke or TIA.
The number of events and participants were abstracted. Estimates of effect were calculated with random-effects model and confirmed by a fixed-effects model and expressed as odds ratio (OR) and risk difference (RD). Statistical significance was set at p < 0.05 (2-tailed). Heterogeneity was assessed by a Q-statistic and I2 test. Significant heterogeneity was considered present for p values< 0.10 or an I2> 50%. Meta-regressions were performed to test the influence of baseline characteristics (age, male sex, hypertension, diabetes, dyslipidemia, smoke, coronary artery disease, symptoms and year of publication) as potential effect modifiers (significance at p < 0.05). Publication bias was assessed using funnel plots, Egger’s test and trim and fill method. All data analyses were performed using Reviewer Manager (RevMan) Version 5.2 and Prometa Software Version 2 [
Of 7200 articles identified by the initial search, 64 were retrieved for more detailed evaluation. Twenty studies directly comparing CAE and CEA and providing the number of new brain lesions at DWI were finally included in the analysis (
N |
CAS | CEA | RCT | Age | Men | Hypertension | Diabetes | Dyslipidemia | Smoke | CAD | Symptoms | EPD | Stent type | CEA procedure | ||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Flach et al[ |
2004 | 44 | 21 | 23 | No | 69 | 80% | - | - | - | - | - | 100% | Yes | Both | Selective shunting |
Garcia-Sanchez et al[ |
2004 | 20 | 10 | 10 | No | 66 | 95% | 70% | 40% | 65% | 80% | 15% | 100% | No | Closed cell | Shunting in all |
Poppert et al[ |
2004 | 129 | 41 | 88 | No | 69 | 68% | 87% | 33% | 58% | 38% | 35% | 47% | No | Closed cell | Shunting in all |
Roh et al[ |
2005 | 48 | 22 | 26 | No | 63 | 96% | - | - | - | - | - | 77% | No | Closed cell | Shunting in all |
Lihara et al[ |
2006 | 231 | 92 | 139 | No | 69 | 91% | 74% | 37% | 14% | 48% | 35% | 54% | Yes (all) | Both | Selective shunting |
Faraglia et al[ |
2007 | 75 | 35 | 40 | No | 70 | 72% | 83% | 23% | 33% | 78% | 27% | 25% | Yes (all) | Both | Selective shunting |
Lacroix et al[ |
2007 | 121 | 61 | 60 | No | 72 | - | - | - | - | - | - | 51% | Yes (all) | Closed cell | Shunting in all |
Tedesco et al[ |
2007 | 47 | 27 | 20 | No | 68 | 100% | 85% | 40% | 81% | 78% | 60% | 62% | Yes (all) | Open cell | Selective shunting |
Posacioglu et al[ |
2008 | 115 | 56 | 59 | No | 66 | 71% | 88% | 26% | 36% | 52% | 52% | 53% | Yes (all) | Closed cell | No shunting |
Skjlland et al[ |
2009 | 58 | 28 | 30 | No | 66 | 81% | - | - | - | 43% | - | 53% | Yes (all) | - | Shunting in all |
Zhou et al[ |
2009 | 168 | 68 | 100 | No | - | - | - | - | - | - | - | - | Yes (all) | Both | Shunting in all |
Bonati (ICSS-MRI) et al[ |
2010 | 231 | 124 | 107 | Yes | 60 | 70% | 69% | 21% | 64% | 76% | 22% | 100% | Yes (45%) | - | - |
Capoccia et al[ |
2010 | 43 | 23 | 20 | No | 71 | 63% | 86% | 49% | 43% | 52% | 36% | 0% | Yes (all) | Closed cell | Selective shunting |
Mitsuoka et al[ |
2011 | 45 | 20 | 25 | No | - | - | - | - | - | - | - | 87% | Yes (all) | Both | - |
Wasser et al[ |
2011 | 49 | 21 | 28 | No | 67 | 79% | 88% | 37% | 77% | 58% | 20% | 53% | Yes (38%) | - | Selective shunting |
Yamada et al[ |
2011 | 81 | 56 | 25 | No | 72 | 89% | 82% | 40% | 54% | - | 39% | 62% | Yes (all) | Both | Shunting in all |
Akutsu et al[ |
2012 | 104 | 41 | 63 | No | 72 | 91% | 74% | 34% | 76% | 61% | 26% | 54% | Yes (all) | Both | Selective shunting |
Felli et al[ |
2012 | 300 | 150 | 150 | No | - | - | - | - | - | - | - | 50% | Yes (all) | Both | - |
Cho et al[ |
2014 | 45 | 16 | 29 | No | 70 | 77% | 84% | 27% | 16% | 38% | - | - | - | - | - |
Kuliha et al[ |
2015 | 150 | 77 | 73 | Yes | 66 | 70% | 87% | 43% | 70% | 26% | 38% | 58% | Yes (96%) | Closed cell | Selective shunting |
*This number indicates the total number of CAS and CEA procedures performed in each study and for which the DWI is available.
**The reported characteristics refer to the overall population included in the original study and not to the 58 included in the meta-analysis because of DWI availability.
Abbreviations: CAD = coronary artery disease; CAS = carotid artery stenting; CEA = carotid endarterectomy; EPD = embolic protection device; ICSS-MRI = international carotid stenting study-magnetic resonance imaging; RCT = randomized clinical trial
The incidence of new DWI lesions was significantly increased with CAS compared with CEA (40.3% [399 of 989] versus 12.2% [136 of 1115]; 20 studies; 2104 patients; OR 5.17; 95% CI, 3.31–8.06; p<0.00001; Table B in
Random effects odds ratio and 95% confidence interval for the primary endpoint of new ischemic lesions at DWI after CAS and CEA.
Post-procedural death was reported only in two patients of the CAS group and in none of the CEA group (Table B in
Stroke was significantly higher after CAS then CEA (17 studies; 1833 patients; OR 2.01; 95% CI, 1.14–3.55; p = 0.02;
Random effects odds ratio and 95% confidence interval for the post-procedural incidence of stroke after CAS and CEA.
None of the baseline characteristics analyzed (age, male sex, hypertension, diabetes, dyslipidemia, smoke, coronary artery disease, symptoms and year of publication;
The overall effect size (OR) of new DWI lesion, stroke and stroke or TIA was confirmed when meta-analyses were repeated removing 1 study at the time (Table D in
The funnel plots and Egger’s test (p = 0.15, p = 0.77 and p = 0.93 for new DWI lesion, stroke and stroke or TIA respectively) did not show any significant publication bias, in all the analyses performed. Trim and fill method confirmed the absence of significant publication bias for new DWI lesion (7 studies trimmed, OR 3.54 2.26–5.56; p<0.0001), stroke (0 studies trimmed, OR 1.9 1.1–3.28, p = 0.02) and stroke or TIA (1 study trimmed, OR 2.22 1.33–3.73, p = 0.001).
The present updated meta-analysis focused on new cerebral ischemic lesions detected by DW-MRI showing that they occur more frequently after CAS than CEA (40.3% versus 12.2%). Moreover, an increased post-procedural rate of ischemic cerebrovascular events (stroke or TIA) was observed in the studies included in this meta-analysis.
A previous meta-analysis including only 6 studies showed that, despite new DWI lesions were significantly increased in CAS versus CEA, the incidence of stroke or death was non-significantly increased [
The results here described should be interpreted on the basis of the following considerations.
First, several studies included in this analysis are dated and the CAS procedures have increasingly ameliorated during these years [
Second, it is important to mention that the present study was not designed to generally compare CEA and CAS for all outcomes, therefore all the complications of CEA (such as myocardial infarction, cranial nerve injury, etc) have not been considered.
Third, the impact of these new DWI lesions remains to be defined, indeed, the post-procedural TIA or stroke events are very small compared to the incidence of new DWI lesions, and often also observed in patients without DWI lesions [
Fourth, the number, the volume and the localization (ipsilateral, contralateral or bilateral) of new lesions seem to be greater after CAS and seem to have an important role on the long-term outcomes [
Fifth, it cannot be excluded that differences in the baseline characteristics of patients undergoing CAS or CEA could have affected the results described because the present study comprehensively analyzes the unadjusted incidence of new brain lesions and the majority of studies included are non-randomized. Therefore, whether the increased number of new lesions after CAS was because more patients who had high cardiovascular risk profiles were assigned to stenting is unclear. However, the analysis from the only 2 randomized trials is consistent with the overall result showing a significant increased number of new microembolizations after CAS (OR 3.94; p<0.00001;
Although some data question the equivalence of CAS and CEA, no doubts exist about CAS advantages (minimal invasiveness, absence of general anesthesia and surgical incision, absence of some complications as cranial nerve injury and wound problems, etc.) and its very important value for specific clinical settings (i.e. high risk or inoperable patients, restenosis after CEA, previous neck surgery or radiation therapy, anatomical high bifurcation or extended lesions) [
Despite the limitations of the present study, mainly related to differences in study design [
CAS is associated with an increased incidence of new post-procedural DWI lesions compared with CEA (40.3% vs 12.2%; OR 5.17; 95% CI, 3.31–8.06; p<0.00001). This greater amount of ischemic burden may also reflect a higher rate of cerebral events after CAS. However, whether recent technical advances mainly in the field of CAS could potentially reduce these adverse ischemic events still remains to be evaluated.
Supplementary information including: PRISMA Checklist
(DOCX)