Comments, Opinions, and Reviews

Transcripción

Comments, Opinions, and Reviews
Systematic Review of the Perioperative Risks of Stroke or
Death After Carotid Angioplasty and Stenting
Emmanuel Touzé, PhD; Ludovic Trinquart, MSc; Gilles Chatellier, PhD; Jean-Louis Mas, MD
Downloaded from http://stroke.ahajournals.org/ by guest on September 29, 2016
Background and Purpose—Carotid angioplasty and stenting (CAS) has not been shown to be as safe as carotid
endarterectomy (CEA) with regard to the risks of periprocedural complications, but beyond the perioperative period, the
risks are comparable, suggesting that CAS may be an acceptable option in selected patients. However, risk factors for
perioperative stroke and death have not been clearly established. We aimed to estimate the 30-day absolute risks of
stroke or death after CAS and investigate sources of heterogeneity.
Methods—We sought articles published between January 1990 and June 2008 by using MEDLINE, EMBASE, the
COCHRANE databases, hand-searching, abstract books from conferences, and official websites. Two reviewers
independently and in duplicate selected articles on the risks of CAS, irrespective of the type of treatment, study design,
setting, or language. The 2 reviewers abstracted data and assessed the quality of the studies.
Results—Two hundred six independent studies (with 54 713 patients) were included. The overall 30-day risk of stroke or
death was 4.7% (95% CI, 4.1 to 5.2) with substantial heterogeneity across studies. Symptomatic patients were about
twice as likely as those with asymptomatic stenoses to have complications. The 30-day risk of stroke or death was 7.6%
(3.6 to 9.1) in symptomatic and 3.3% (2.6 to 4.1) in asymptomatic patients. Risks increased with age, hypertension, and
history of coronary artery disease; were unrelated to sex and the presence of contralateral carotid occlusion; and were
lower in patients who had carotid restenosis after CEA and in those treated with the use of a cerebral protection device.
Risks have also decreased over time.
Conclusions—Risks of CAS vary substantially across studies. Risks are overall higher than those of CEA in symptomatic
patients. Some factors are likely to help select good candidates for CAS. (Stroke. 2009;40:e683-e693.)
Key Words: stroke 䡲 carotid disease 䡲 stenting 䡲 angioplasty 䡲 atherosclerosis 䡲 systematic review
E
xtracranial internal carotid artery stenosis accounts for
15% to 20% of ischemic strokes, depending on the
population studied.1 The efficacy of carotid endarterectomy
(CEA) to prevent stroke in patients with carotid stenosis is
well established, particularly in those who have symptomatic
stenosis.1–3 Carotid angioplasty and stenting (CAS), a potential alternative treatment to CEA, has been evaluated in a few
randomized trials and many nonrandomized studies and
involving many specialists, including neurologists, radiologists, cardiologists, vascular surgeons, and neurosurgeons,
most of whom have already implemented the technique in
their clinical practice.4 However, recent randomized trials and
meta-analyses failed to demonstrate that CAS is as safe as
CEA with regard to the risks of periprocedural complications,4 –12 and current guidelines recommend that CAS should
not be used in good surgical candidates.2,3,13 Nevertheless, the
clinical trials have also shown that beyond the perioperative
period, the risk of ipsilateral stroke is very low and comparable in CAS and CEA patients,10,14,15 suggesting that CAS
may be an acceptable option in selected patients who have a
low risk of periprocedural complications. However, there is
currently no means to select good candidates for CAS. Moreover, although CAS is widely used in some centers, it is
unknown whether the absolute risk of CAS observed in randomized trials can be generalized to everyday clinical practice.
The risks of complications after CEA and their relations
with different subgroups have been estimated in several
studies and meta-analyses,16 –20 but no similar data exist for
CAS. Some studies have shown that the risk of complications
after CAS is likely to be related to some patient characteristics and technical aspects. However, the number of complications observed in individual studies was usually small,
precluding any reliable conclusion. Moreover, many studies
have focused on patients with a perceived high surgical risk,
hypothesising that those patients should be good candidates
for CAS.4,21 However, it is possible that comorbidities associated with a greater perioperative risk with CEA also
increase the periprocedural risk with CAS.
Received July 8, 2009; final revision received August 25, 2009; accepted September 4, 2009.
From the Université Paris Descartes, INSERM U894 (E.T., J.-L.M.), Hôpital Sainte-Anne, Service de Neurologie, and INSERM CIE4 (L.T., G.C.),
Assistance Publique–Hôpitaux de Paris, Unité de recherche clinique, Hôpital Européen Georges Pompidou, Paris, France.
The first 2 authors contributed equally to the data collection, analysis, and writing of the article.
Correspondence to Emmanuel Touzé, MD, PhD, Université Paris Descartes, INSERM U894, Department of Neurology, Hôpital Sainte-Anne, 1 rue
Cabanis, 75014 Paris, France. E-mail [email protected]
© 2009 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org
DOI: 10.1161/STROKEAHA.109.562041
e683
e684
Stroke
December 2009
Table 1.
Search Strategy in MEDLINE and EMBASE
PubMed search strategy
(“Carotid stenosis”关Mesh兴 AND (“stents”关Mesh兴 OR “angioplasty”关Mesh兴
OR “angioplasty, balloon”关Mesh兴) AND (“treatment outcome”关Mesh兴 OR
“postoperative complications”关Mesh兴 OR “myocardial infarction”关Mesh兴
OR “stroke”关Mesh兴 OR “brain ischemia”关Mesh兴 OR “death”关Mesh兴 OR
“death, sudden, cardiac”关Mesh兴 OR “mortality”关Mesh兴)) OR (“carotid
stenosis” AND (“carotid angioplasty” OR “stent”*) AND (“stroke” OR
“myocardial infarction” OR “death” OR “mortality”) AND
关(“1990”关PDat兴:”2008/06”关PDat兴) AND (“humans”关Mesh兴)兴)
EMBASE search strategy
(“Carotid artery obstruction”/exp AND (“stent”/exp OR “angioplasty”/exp
OR “percutaneous transluminal angioplasty”/exp) AND (“treatment
outcome”/exp OR “postoperative complication”/exp OR “heart
infarction”/exp OR “cerebrovascular accident”/exp OR “stroke”/exp OR
“brain ischemia”/exp OR “death”/exp OR “sudden death”/exp) NOT
关“review”兴/lim AND 关“humans”兴/lim AND 关1990 –2008兴/py)
We therefore systematically reviewed studies reporting the
risk of stroke, death, and myocardial infarction (MI) after
CAS to estimate the absolute risks and investigate any
relation between observed risks and study design, population,
clinical factors, and technical aspects.
Methods
Before conducting the review, we developed a protocol containing
the background and objectives, along with an outline of the proposed
search methods and plans for collecting and analyzing data. The
manuscript was prepared in accordance with the MOOSE
guidelines.22
Selection Criteria and Search Strategy
Studies were eligible for review if: (1) they enrolled patients with
symptomatic and/or asymptomatic stenoses located in the region of
the carotid bifurcation; (2) patients were treated by angioplasty
irrespective of the type of treatment (balloon angioplasty without
stenting or stenting), arterial route, and the use of cerebral protection;
and (3) the number of events (stroke, MI, or death) could be
extracted. Studies that enrolled a specific population group only
(restenosis after CEA, postradiotherapy stenosis, fibromuscular dysplasia, carotid dissection, and patients treated in an emergency
context) were excluded.
We sought articles published between January 1990 and June 2008
on the risks of stroke, death, or MI after CAS, irrespective of the
study design, setting, or language. Electronic searches were performed using MEDLINE, and EMBASE with both medical subject
heading terms and text words (Table 1) and the COCHRANE
Library database (CENTRAL and DARE). We hand-searched the
reference lists of all included articles, any relevant review articles,
our personal files, and the contents pages of the 3 journals from
which most eligible articles were identified in the electronic search
(Journal of Vascular Surgery, Journal of Endovascular Therapy, and
Catheter Cardiovascular Interventions). To identify recent studies
not yet published as complete articles, we also searched books of
abstracts from recent conferences (Joint World Congress on Stroke
2006, American Heart Association International Stroke Conferences
2007 and 2008, the European Stroke Conferences 2007 and 2008, the
Cardiovascular and Interventional Radiological Society of Europe
meetings 2006 and 2007, the Transcatheter Cardiovascular Therapeutics meetings 2006 and 2007, the American College of Cardiology Scientific sessions 2007 and 2008, and the Society of Interventional Radiology meetings 2007 and 2008) and the clinical trial
registration (www.clinicaltrials.gov), the US Food and Drug Admin-
istration (www.fda.gov), and the European Medicines Agency (www.
emea.europa.eu) websites.
Selection of Studies and Data Collection
Two reviewers independently and in duplicate assessed the eligibility
of citations identified by the search strategy from titles and then from
abstracts. At each step, discrepancies were resolved by discussion.
Final selection was made after reviewing full-text articles that were
retrieved for all studies either that met the selection criteria or for
which there was uncertainty regarding selection as per the abstract.
In cases of multiple publications pertaining to the same population,
that which reported the largest number of patients was chosen for the
absolute risk analysis. Additional subgroup data of the SPACE trial
were obtained from the authors.8 The 2 reviewers extracted the data
by means of a standardized form (available from the authors). Study
quality was assessed according to an existing scheme23 that we
adapted to our context and that included the following list of criteria:
(1) design (randomized trial vs cohorts/registries), (2) setting (singlecenter vs multicenter study), (3) patient enrollment (prospective vs
retrospective and consecutive vs nonconsecutive), (4) description of
the population (adequate vs inadequate), and (5) outcome measurement (systematic assessment by a neurologist after the procedure,
yes vs no). The description of the population was deemed adequate
when the sampling frame, recruitment, inclusion and exclusion
criteria, and the baseline study sample characteristics were adequately described. Systematic assessment by a neurologist referred to
every patient being seen by a neurologist at 30 days (30-day
outcomes) or before discharge (periprocedural and in-hospital
events), whether the patient had an event or not.
Data Synthesis and Data Analysis
The primary outcomes were the 30-day risks of stroke; stroke or
death; and stroke, MI, or death. The secondary outcomes were
in-hospital and periprocedural (within 24 hours) risks. When the
timing of assessment of complications was unclear without systematic follow-up at 30 days, we considered events as periprocedural
complications. Combined estimates of risk were calculated separately for the different outcomes. Each individual proportion was
first transformed into a quantity with the Freeman-Tukey variancestabilizing transformation.24 A weighted mean of the transformed
proportions was computed by using a DerSimonian-Laird randomeffects model.25 The combined proportion was calculated as the
back-transform of this weighted mean.26
To explore sources of heterogeneity, we first performed subgroup
comparisons according to the following factors: clinical presentation
(symptomatic vs asymptomatic; stroke vs transient ischemic attack;
cerebral vs ocular event), age (⬎75 to 80 vs ⬍75 to 80 years), sex,
diabetes mellitus, coronary artery disease (CAD), peripheral arterial
disease (PAD), contralateral carotid occlusion, restenosis after CEA
versus de novo lesion, plaque structure (ulcerated vs smooth,
presence of calcification), timing for CAS (⬍14 days vs ⬎14 days
after cerebral ischemic event), side of the treated lesion, and cerebral
protection device use. Those comparisons were done within studies.
We calculated combined relative risks (RRs) for all studies by using
a fixed-effect meta-analysis, according to the Mantel-Haenszel
method, or by using a DerSimonian-Laird random-effects meta-analysis, where appropriate. Then we performed indirect comparisons of
pooled absolute risks according to clinical presentation and the study
quality items defined earlier and assessed potential changes of risk
over time from a meta-regression analysis. We used a logisticnormal model that specified the binomial distribution of the dependent variable (30-day risk of stroke or death) and a random effect to
account for shared variance within the study.27 The midcohort year,
defined as the midpoint of the inclusion period, was calculated for
each study if the inclusion period was available and considered as a
covariate. We assessed publications biases by means of a simple
visual analysis of funnel plots in the meta-analysis of absolute risks,
as there is no validated statistical test to detect asymmetry, and used
funnel plots and Egger’s test in the subgroup comparisons.28 In all
Touzé et al
Risks After Carotid Angioplasty and Stenting
e685
Figure 1. Flow chart for selection of studies.
analyses, inconsistency of findings across studies was assessed with
Cochran’s Q statistic and the I2 statistic with associated 95% CI, the
latter being the percentage of variability that is due to between-study
heterogeneity rather than sampling error (chance).29,30 According to
the Cochrane handbook, heterogeneity was classified as moderate
(I2ⱖ30%), substantial (I2ⱖ50%), or considerable (I2ⱖ75%).31 We
considered a 2-sided probability value ⬍0.05 as significant. Statistical analysis was performed with SAS version 9.1 and MIX
(http://mix-for-meta-analysis.info).
Results
Of the 1796 articles identified from our electronic search in
MEDLINE and EMBASE, 605 abstracts were screened and
457 articles were retrieved for assessment in full text (Figure 1).
We identified 53 additional articles or abstracts from other
sources. Among the 510 references analyzed in detail, 206
independent studies were eligible (133 for absolute risk only,
62 for absolute risk and subgroups, and 11 for subgroups
only). Because of multiple publications of some registries
with different subgroup analyses, the 206 independent studies
resulted in 234 reports (212 full articles, 19 abstracts, 2 US
Food and Drug Administration documents, and 1 web publication) that were finally relevant to our analysis. Summarized
characteristics of the included studies are given in Table 2,
and the list of references and the characteristics of individual
reports are available in supplemental Table I, available online
at http://stroke.ahajournals.org. Among the 206 independent
studies (54 713 patients), there were 10 randomized clinical
trials (RCTs) comparing CAS with CEA (1613 patients),5,7,8,21,32–37 3 RCTs comparing different strategies in
patients treated by CAS (144 patients),38 – 40 and 193 registries
(52 956 patients). There were 32 studies (2922 patients) in
which 95% or more of patients had symptomatic stenosis, 2
studies (136 patients) in which 95% or more of patients had
asymptomatic carotid stenosis, and 172 studies (51 655 patients) with both symptomatic and asymptomatic patients.
Roughly half (51%) of the studies started enrolling patients
before 2000.
As shown in Table 2, 83% of studies had a single-center
setting and 40% were stated as prospective. The description
of the population was adequate in 46%, and assessment of
outcomes was done by an independent neurologist in 40% of
studies published as a full article. Both a fully described
population and neurologic assessment of outcomes were
found in 49 (26%) of studies published as a full article.
Among the 172 studies that enrolled symptomatic and asymptomatic patients, 36 (21%) reported the risks of CAS stratified
according to clinical presentation. Among the 173 studies that
clearly reported the type of treatment performed, there were
161 (93%) studies in which ⬎90% of patients were treated
with stenting.
The main characteristics of RCTs and registries were very
similar with regard to age (median, 69 vs 70 years), proportion of men (median, 71% vs 71%), proportion of patients
with contralateral carotid occlusion (median, 10% vs 10%),
and proportion of patients with CAD (median, 57% vs 61%).
The proportion of symptomatic patients was higher in RCTs
than in registries (median, 81% vs 49%). Conversely, registries were more likely than RCTs to have enrolled patients
with restenosis after CEA (median, 15% vs 8%), to have
patients with diabetes (median, 32% vs 24%), and to have
treated patients with the use of cerebral protection devices
(median, 83% vs 42%).
Table 3 shows the pooled estimates of the absolute risks
according to the timing of the outcome assessment. The
30-day risk of stroke was 3.9% (95% CI, 3.4 to 4.4; 118
studies; 27 186 patients); that of stroke or death was 4.7%
(95% CI, 4.1 to 5.2; 113 studies; 25 237 patients); and that of
stroke, death, or MI was 5.3% (95% CI, 4.6 to 6.0; 63 studies;
17 291 patients). Respective in-hospital and periprocedural
risks were slightly lower. There was, however, substantial
heterogeneity across studies. Exclusion of the abstracts or
postmarketing studies that might have included patients also
published in individual studies did not change the estimates
(data not shown).
Regarding study quality, meta-regression analyses showed
that the 30-day risk of stroke or death was unrelated to study
setting (multicenter 4.8% vs single-center, 4.6%, P⫽0.77),
and consecutive enrollment (yes 4.6% vs no 4.8%, P⫽0.89).
However, the risk was higher when there was an adequate
description of the population (yes 5.2% vs no 4.0%, P⫽0.04),
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December 2009
Table 2. Quality, Population Characteristics, and Technical
Aspects of the Included Studies
No. of
Studies (%),
Total⫽206*
No. of
Patients (No.
of Procedures)
Study quality
Single center
RCT (other)†
34 898 (35 502)
No. of
studies
included
118
113
63
19 815 (20 684)
10 (5)
1613 (1613)
No. of
patients
27 186
25 237
17 291
28 149
26 145
17 858
3 (1)
144 (144)
52 956 (54 430)
No. of
procedures
Prospective
83 (40)
24 878 (25260)
Pooled risk
(95% CI)
Retrospective
42 (20)
8580 (8881)
Not clear
81 (40)
21 255 (22045)
Patient enrollment
Consecutive
Stroke, MI,
Death
36 (17)
193 (94)
Registry
Stroke, Death
170 (83)
Design
RCT (CEA vs CAS)
Stroke
30-day
events
Setting
Multicenter
Table 3. Pooled Estimates of the Absolute Risks of Stroke,
Death, or MI According to the Timing of the Outcome
Assessment After CAS
3.9% (3.4 to 4.4)
4.7% (4.1 to 5.2)
5.3% (4.6 to 6.0)
⬍0.0001
⬍0.0001
⬍0.0001
67% (60 to 73)
69% (62 to 74)
64% (52 to 72)
No. of
studies
included
53
48
19
P(het)
I2 (95% CI)
119 (58)
29 485 (30250)
87 (42)
25 228 (25936)
Sampling frame described
154 (75)
38 056 (39 354)
Inclusion criteria described
140 (68)
36 487 (37 429)
Baseline characteristics described
132 (64)
34832 (3552)
No. of
patients
11 694
7912
1723
Assessment by a neurologist
79 (39)
26 286 (26 835)
No. of
procedures
12 073
8243
1806
Definition of stroke outcome
given
87 (43)
37 499 (38 292)
At least 1 neurologist in the list
of authors
66 (32)
9075 (9410)
Not clear
Description of population
Outcome assessment
No. of
Studies With
Data Available
In-hospital
events
Pooled risk
(95% CI)
Median Value (IQR)
No. of patients
206
90 (41 to 204)
No. of procedures
206
94 (43 to 215)
Percent men
179
71 (65 to 80)
Mean age, y
180
70 (67 to 71)
Percent symptomatic
180
50 (33 to 78)
Percent diabetic patients
128
31 (24 to 38)
Percent patients with carotid
restenosis
95
14 (7 to 24)
Percent patients with
postradiation carotid stenosis
47
5 (2 to 9)
Percent patients with CAD
104
60 (40 to 71)
Percent patients with PAD
44
28 (20 to 37)
Percent patients with
contralateral carotid occlusion
79
10 (6 to 14)
No patient treated with cerebral
protection, n studies (%)
201
54 (27)
All patients treated with cerebral
protection, n studies (%)
201
71 (35)
Percent successful procedures,
median (IQR)
109
98 (97–100)
IQR indicates interquartile range.
*Also include abstracts.
†RCTs comparing different strategies in patients treated by CAS.
4.6% (3.5 to 5.9)
⬍0.0001
⬍0.0001
54% (36 to 67)
30% (0 to 60)
No. of
studies
included
53
40
13
No. of
patients
9003
3893
979
No. of
procedures
9413
4199
1006
0.11
Periprocedural
events*
Pooled risk
(95% CI)
P(het)
Technical aspects
4.1% (3.3 to 5.0)
56% (41 to 68)
P(het)
I2 (95% CI)
Population characteristics
3.9% (3.2 to 4.6)
I2 (95% CI)
3.5% (2.7 to 4.4)
3.7% (2.6 to 5.0)
⬍0.0001
⬍0.0001
71% (61 to 78)
66% (53 to 76)
4.0% (2.6 to 5.7)
0.23
21% (0 to 59)
P(het) indicates the P value associated with the ␹2 test for heterogeneity; I2,
percentage of the variability in effect estimates that is due to heterogeneity
rather than sampling error (chance). Combined estimates of risk were
calculated separately for the different outcomes. Each individual proportion was
first transformed into a quantity with the Freeman-Tukey variance-stabilizing
transformation.24 A weighted mean of the transformed proportions was
computed with a DerSimonian-Laird random-effects model.25 The combined
proportion was calculated as the back-transform of this weighted mean.
*Also includes events of uncertain timing.
in the case of prospective enrollment (yes 5.2% vs no 4.2%,
P⫽0.07), and when the assessment was done by a neurologist
(yes 5.4% vs no 4.1%, P⫽0.02). We did not find evidence for
publication bias in the visual analysis of the funnel plots of
the study sample size against the absolute risk of stroke or
Touzé et al
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Figure 2. Pooled RRs of stroke and stroke or death for different subgroups. P(het) indicates the probability value associated with
the Cochran ␹2 statistical test for heterogeneity; I2, percentage of the variability in effect estimates that is due to heterogeneity
rather than sampling error (chance); NA, not assessable; TIA, transient ischemic attack; CABG, coronary artery bypass graft; and
P(sig), P value for significance. We used a fixed-effect model to calculate the pooled estimates, except where P(het)⬍0.10 or
I2⬎30%, in which case a random-effects model was used. See supplemental Figures II and III for each individual meta-analysis.
Outcomes assessed at 30 days, at discharge, during the procedure, or when timing was unknown were pooled. The comparison
is yes vs no unless indicated otherwise. A, Pooled RR (95% CI) for stroke or death (see also supplemental Figure II). B, Pooled
RR (95% CI) for stroke (see also online-only Figure III).
death, as there were as many smaller studies with high and
low risks of complications (supplemental Figure I, available
online at http://stroke.ahajournals.org). Findings were similar
with stroke and with stroke, MI, and death (data not shown).
Figure 2 shows a summary of the pooled RRs of stroke and
stroke or death resulting from CAS for the different prespecified subgroup analyses separated in terms of clinical symp-
toms, patient characteristics (including vascular risk factors
and past medical history), stenosis features, and technical
factors. (Forest plots of the corresponding analyses are
available in supplemental Figures II and III.) Symptomatic
stenosis (RR⫽1.86; 95% CI, 1.61 to 2.14), cerebral event
versus ocular event (RR⫽2.28; 95% CI, 1.08 to 4.77), age
⬎75 to 80 years (RR⫽1.93; 95% CI, 1.66 to 2.24), CAD
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December 2009
Figure 3. Absolute 30-day risk of stroke
or death (%) after CAS in 91 studies
(18 538 patients) according to the midcohort year, together with a summary
random-effects meta-regression. The area
of each circle is inversely proportional to
the variance of the absolute risk.
(RR⫽1.41; 95% CI, 0.97 to 2.06), history of coronary artery
bypass graft (RR⫽2.21; 95% CI, 1.03 to 4.72), and PAD
(RR⫽2.04; 95% CI, 0.92 to 4.52) were associated with a
higher risk of stroke or death after CAS. There was also a
trend for a higher risk of complications in patients who had
calcified plaque. Conversely, the risk of stroke or death after
CAS was lower in patients treated for carotid disease due to
restenosis after CEA than in those treated for atherosclerotic
carotid stenosis (RR⫽0.45; 95% CI, 0.28 to 0.71). The use of
cerebral protection systems was associated with a lower risk
of stroke or death (RR⫽0.57; 95% CI, 0.43 to 0.76). The risk
of stroke or death was not related to sex, contralateral carotid
occlusion, diabetes mellitus, plaque ulceration, timing for
CAS, and side of the treated lesion. Similar results were
found for stroke outcome, except that hypertension was
significantly associated with a higher risk of complications
(RR⫽1.86; 95% CI, 1.30 to 2.68). In contrast to the substantial heterogeneity found in the pooled estimates of absolute
risks, there was either no or only moderate heterogeneity in
these combined estimates of the RRs. We did not find
evidence for publication biases in these analyses on the
funnel plots or with the Egger test (data not shown).
The pooled 30-day risk of stroke was 6.3% (95% CI, 4.8 to
8.0) in studies with a midcohort year before 1998, 5.0% (95%
CI, 4.1 to 5.9) in those with a midcohort year between 1998
and 2002, and 3.9% (95% CI, 3.0 to 4.9) in those with a
midcohort year after 2002. Meta-regression analysis with
midcohort year as the covariate showed a significant decrease
in the 30-day risk of stroke or death over time, corresponding
to a RR reduction of ⬇6% per year (91 studies, P⬍0.0001;
Figure 3). A similar result was found when publication year
was used instead of midcohort year (P⬍0.0001) or when
stroke was considered instead of stroke or death (data not
shown).
Figure 4 shows the pooled 30-day absolute risks of stroke
or death stratified according to clinical indication and further
stratified according to study design and whether outcomes
were assessed by a neurologist or not. In patients with
symptomatic stenosis, the overall absolute 30-day risk of
stroke or death was 7.6% (95% CI, 6.3 to 9.1; 42 studies;
4910 patients). That risk was higher in RCTs (10.8%; 95%
CI, 6.8 to 15.5) than in registries that enrolled symptomatic
patients only (7.3%; 95% CI, 5.3 to 9.6; P⫽0.16) and than in
subgroups of symptomatic patients enrolled in other registries
(7.0%; 95% CI, 5.2 to 9.0; P⫽0.04). The absolute 30-day risk
of stroke or death was nonsignificantly higher in studies
where there was an independent neurologic assessment
than in those where the method of assessment of outcomes
was not clearly performed by an independent neurologist.
For patients with asymptomatic stenosis, there was only 1
RCT in which the 30-day risk of stroke or death was not
clearly assessed,34 and 1 registry enrolled asymptomatic
patients only.41 The overall absolute risk of stroke or death
was 3.3% (95% CI, 2.6 to 4.1; 23 studies; 8504 patients).
As for symptomatic stenosis, risks were nonsignificantly
higher in studies where there was an independent neurologic
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Figure 4. Pooled 30-day risk of stroke or death after CAS stratified according to clinical indication and further stratified according to
study design and whether outcomes were assessed by a neurologist or not. The dotted line corresponds to the 30-day risk combined
across RCTs and all registry data. There was an independent neurologic assessment in all RCTs. Some RCTs could not be included in
this analysis because the 30-day stroke or death outcome was unavailable.
assessment. All of these findings were similar when we used
the presence of at least 1 neurologist in the list of authors as
a marker of quality instead of independent neurologic assessment (data not shown).
Discussion
First, we have shown that the overall 30-day risk of stroke or
death after CAS is ⬇5%, but it varies substantially across
studies. Those variations may result from differences in case
mix, design, quality of the study, and skill of the interventionists. Second, the risks of CAS depend on the clinical
indication, with symptomatic patients being about twice as
likely as those with asymptomatic stenosis to have complications and on patient characteristics that are also high
surgical risk factors, including age, hypertension, and history
of CAD (including coronary artery bypass graft). Conversely,
other established high surgical risk factors either did not seem
to influence the risk of complications due to CAS (female sex
and contralateral carotid occlusion) or were even associated
with a lower risk (carotid restenosis after CEA). Therefore,
our results strongly suggest that there are simple clinical
factors that are likely to help in selecting good candidates for
CAS in future clinical trials comparing that technique with
CEA and eventually in clinical practice. Finally, our results
suggest that risks have decreased over time, and the use of a
cerebral protection device is associated with a lower risk of
complications.
We identified 206 studies that reported risks of CAS on
54 713 patients. It should be noticed that RCT patients
accounted for only 3% of the overall population, underlining
how much the technique has been implemented in clinical
practice despite a low level of evidence. Because of substantial heterogeneity between studies, our pooled estimates of
absolute operative risks cannot be interpreted in a straightforward manner. However, the 95% CI obtained from a
random-effect meta-analysis well describes uncertainty in the
average risk. For instance, for all studies, the 30-day risk of
stroke or death was, with 95% confidence, at least equal to
4.1% and as high as 5.2%. Interestingly, a similar heterogeneity was found in previous systematic reviews for the risks
of CEA.16 –18
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There are several sources of heterogeneity across studies
that we were able to identify. It is well established that the
benefit of CEA strongly depends on the clinical indication,
with greater benefit observed in symptomatic compared with
asymptomatic patients, and that there is a higher risk of
perioperative complications in symptomatic patients.17,18,42,43
A previous systematic review showed that only ⬇25% of
studies on CEA stratified their results according to whether
the patients were asymptomatic or symptomatic.16 Similarly,
we found that only 21% of CAS studies reported risks
stratified according to clinical indication. We have shown
that, as for CEA, symptomatic patients are about twice as
likely as asymptomatic patients to have complications after
CAS. This result is based on subgroup analyses, ie, comparing symptomatic and asymptomatic patients within the same
studies, and we did not find heterogeneity across studies. For
symptomatic patients, we found that the 30-day risk of stroke
or death of CAS was 7.6%, with the lower limit of the 95%
CI being 6.3%, which is higher than the 30-day risk resulting
from CEA found in a previous systematic review (5.1%; 95%
CI 4.6 to 5.6).16 That level of risk is also higher than the risk
threshold established by the ad hoc committees of the
American Heart Association Stroke Council guidelines, recommending that the combined risk of stroke and death
resulting from CEA should be no more than 5% for patients
with transient ischemic attack and 7% for those with stroke.2,3
Although questionable, this comparison of pooled absolute
risks is in full agreement with the meta-analysis of RCTs
comparing CAS with CEA in symptomatic patients and
showing that CAS is associated with a 40% increase in risk of
stroke or death within 30 days.12 We also found that the risk
was higher in RCTs than in registries. It is likely that the
definition of symptomatic stenosis differed across studies,
although this information cannot be easily extracted from
publications (eg, some registries considered stroke that occurred in any territory or at any time lapse). In addition, as for
CEA,18 our results suggest that the quality of neurologic
assessment partly accounts for the observed differences.
Although most patients enrolled in registries had asymptomatic stenosis, we found very limited specific data on the risks
of CAS in those patients. The overall 30-day risk of stroke or
death with CAS was 3.3%, with the lower limit of the 95% CI
being 2.6%. That level of risk is close to that resulting from
CEA (2.8%; 95% CI, 2.4 to 3.2),16 and the 3% risk threshold
established in guidelines for asymptomatic stenosis.2,3
Many registries have focused on patients with a high
surgical risk according to a set of criteria, varying in number
and type, hypothesising that those patients should be good
candidates for CAS.4 Commonly cited factors associated with
higher surgical risk are anatomic factors such as surgically
inaccessible lesions, prior CEA or neck irradiation, old age,
contralateral carotid occlusion, and medical comorbidities.
However, there is no evidence that high surgical risk patients
benefit from any revascularization strategy in comparison
with medical treatment alone.44 Moreover, it is possible that
comorbidities associated with a greater perioperative risk
with CEA also increase the periprocedural risk with CAS.
Studies that addressed whether factors that identify high
surgical risk patients have any impact on the risks of CAS
usually had low statistical power to draw any reliable conclusion. Although previous meta-analyses of RCTs and registries have consistently shown that age has only a small
impact on the risk of complications after CEA,45 elderly
patients are considered a high surgical risk and potential good
candidates for CAS. In fact, we found that age was associated
with an ⬇2-fold increase in risk of complications after CAS,
suggesting that age has more impact on risks of CAS than on
risks of CEA. Interestingly, several studies have shown that
older patients are more likely to have tortuous, severely
calcified vessels that probably increase the risk of embolization during wire manipulation and catheter exchanges at some
stage in CAS.46,47 Another important finding of our analysis
is that, in contrast to CEA, where women have a higher risk
of complications than do men, the risks of CAS are not
related to sex. However, although both very close to 1 and
nonsignificant, the pooled RR of women versus men for
stroke and that for stroke or death are on either side of 1. In
fact, results for stroke were strongly driven by those of the
CAPTURE registry, in which women had a slightly higher
risk of stroke in univariate analysis but not in multivariate
analyses.48 The lack of a sex effect on the risk of CAS has
also been demonstrated in 2 recent studies, published outside
the inclusion period defined in our systematic review.49,50
Inclusion of those results would have not changed our
estimates [stroke pooled RR⫽1.02; 95% CI, 0.87 to 1.27;
P(het)⫽0.87; stroke or death pooled RR⫽0.90; 95% CI, 0.74
to 1.10; P(het)⫽0.84]. Our findings that the risks of CAS do
not depend on contralateral carotid occlusion and are lower in
patients with restenosis after CEA are also important because
they identify a potential target population in whom CAS
could be compared with CEA. Finally, although obtained
from more limited data and in line with previous data on
CEA, our results suggest that the risks of CAS are higher in
patients who had a cerebral compared with an ocular event
and that a previous history of CAD may not be helpful to
select good CAS candidates.
There are potential reasons why risk factors for complications of CEA and CAS may differ. The higher risk of
complications after CEA in women is usually explained by
the fact that the internal carotid artery is smaller than in men,
predisposing to technical errors or early postoperative thrombosis, although this hypothesis has been questioned.51,52
Surgery of carotid restenosis is associated with a high risk of
complications, probably because of important postoperative
fibrotic modifications of the neck tissue and the fact that
restenosis is commonly due to myointimal hyperplasia rather
than atherosclerosis.53 Although in symptomatic patients with
restenosis the long-term benefit of CEA still justifies the
immediate surgical risk and outweighs the risk from medical
therapy alone, the only randomized evidence suggests that
asymptomatic patients with restenosis do slightly better with
medical management.1 Because CAS does not require neck
and arterial incision, sex- or post-CEA–related anatomic
factors are likely to be overcome with CAS. Contralateral
carotid occlusion may compromise compensatory mechanisms and consequently, cerebral perfusion during the clamping of the carotid artery required to perform CEA. The shorter
duration of carotid occlusion during CAS compared with
Touzé et al
CEA could explain the lack of increase in operative risk
during CAS. By contrast, other factors such as age, hypertension, and history of CAD or PAD are strongly associated
with the severity and the extent of atherosclerosis and are
likely to be related to the risk of thromboembolic complications during arterial navigation through the aorta and carotid
artery.
Using meta-regression analysis, we found that the risks of
CAS have decreased over time from 1993 to 2006. This may
result from improvements in CAS technique, devices, or
training and/or a better selection of CAS candidates over
time. The development of devices to protect against embolism during the CAS procedure potentially constitutes an
important advance. Previous systematic reviews of nonrandomized case series showed that the use of cerebral protection devices seems to reduce thromboembolic complications
during CAS54 and to reduce the incidence of new, mostly
asymptomatic, ischemic lesions on diffusion-weighted magnetic resonance imaging performed within 48 hours after
CAS.55,56 Our results obtained from a larger number of
studies are in line with those previous data. However, there
was significant heterogeneity across studies in this analysis.
In fact, the apparent advantage of cerebral protection devices
may be illusory. Indeed, the use of such protection devices
has increased over time, and the apparent protective effect of
those devices may have been confounded by advances in
stenting technique and patient selection over time. It could
also reflect patient selection. In addition, there are still no data
from randomized studies comparing CAS with or without
cerebral protection, and because the protecting devices must
pass through the arterial stenosis, they might themselves
cause complications.
Our study has several potential limitations. First, confounding is a major threat in meta-analyses of observational
studies because subgroup analyses are based on univariate
comparisons. Only a meta-analysis of individual data would
deal with that issue. However, our subgroup analyses were
highly consistent across studies and have plausible pathophysiologic explanations. Moreover, with the use of a
similar approach for CEA, all risk factors for complications found in systematic reviews of registries were replicated in a pooled analysis of individual data from RCTs.16 –20,43
Our findings are therefore unlikely to be spurious. Second,
although we included studies in any language and used
multiple sources of data, publication biases might have
distorted our findings because registries with a low risk of
complications could be more likely to be published.
However, using simple scatterplots, as there is no validated
statistical test to assess publication bias in meta-analyses
of absolute risks, we did not find evidence for publication
biases. Moreover, publication biases are unlikely in the
subgroup analyses because the chance of publication is
unlikely to be related to the results of subgroup analyses,
and we did not find evidence for such biases in the funnel
plots. In addition, RRs usually do not depend on absolute
risk. Third, potential inclusion of duplicated data might
have also distorted our findings.57 However, we thoroughly
examined the authors’ list and setting of each report to
exclude redundant populations as far as possible. We also
e691
performed sensitivity analyses by excluding some large
registries that might have enrolled patients whose data
were also published in small, single-center studies and
found similar results. Fourth, heterogeneity in the quality
of data is another issue in meta-analyses of observational
studies. Although the quality of outcome assessment varied across studies, our findings were not influenced by that
parameter. Fifth, some subgroup analyses (eg, type of
cerebrovascular event, plaque surface aspect, or history of
coronary artery bypass graft) were based on relatively
small numbers of studies and would require additional
confirmatory data. Finally, there are other potential risk
factors for complications that could not be assessed. For
instance, the role of operator experience and the learning
curve could not be assessed in our systematic review,
because there was no standardized definition across studies. Arterial anatomic factors are also likely to influence
the feasibility and risks of CAS.58
In conclusion, the risks of CAS are overall higher than
those of CEA in symptomatic patients. Our findings support
the current guidelines recommending that CAS should not be
used in good surgical candidates. However, they also suggest
that there are factors that are likely to help select good
candidates for CAS in future trials and eventually in clinical
practice.
Acknowledgments
We would to thank very much Peter A. Ringleb and the SPACE
investigators for providing unpublished subgroup data from the trial.
We thank Marta Pasquini, Enrico Flo␤mann, Kaori Flo␤mann, Hu
Chau, Maria Koziak, Daniel Freddy, Didier Leys, Ghislain Nokam,
Barish Turak, and Suzanne Vobecky for their help to extract the data
from non–French-language and non–English-language articles. We
also thank Bernard Beyssen and Olivier Naggara for advising us on
technical aspects and Isabelle Laurent for technical support.
Disclosures
None.
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e694
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Figure I. Scatterplot of the 30-day risk of
stroke or death against the study sample
size (logarithmic scale). The solid line represents the pooled absolute risk obtained
from a random-effect meta-analysis
(4.7%).
Touzé et al
e695
Pooled relative risks of stroke or death according to different subgroups
Page
Subgroup
2
Symptomatic stenosis
3
Qualifying event (stroke vs TIA)
4
Qualifying event (cerebral vs ocular)
5
Delay between symptoms and CAS
6
Age
7
Sex
8
Diabetes
9
Hypertension
10
Coronary heart disease
11
History of CABG
12
Peripheral artery disease
13
Restenosis
14
Contralateral occlusion
15
Plaque calcification
16
Plaque ulceration
17
Stenosis side
18
Cerebral protection device
Figure II. Pooled RRs of stroke or death for the different subgroups. Combined RRs were calculated with a fixed-effect meta-analysis,
according to the Mantel-Haenszel method, or with a DerSimonian-Laird random-effects meta-analysis, where appropriate. Error bars
correspond to the 95% CIs of individual RRs and pooled RR.
December 2009
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Figure II (Continued).
Touzé et al
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Touzé et al
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e702
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Pooled relative risks of stroke according to different subgroups
Page
Subgroup
2
Symptomatic stenosis
3
Qualifying event (stroke vs TIA)
4
Qualifying event (cerebral vs ocular)
5
Delay between symptoms and CAS
6
Age
7
Sex
8
Diabetes
9
Hypertension
10
Coronaryy heart disease
11
History of CABG
12
Peripheral artery disease
13
Restenosis
14
Contralateral occlusion
15
Plaque calcification
16
Plaque ulceration
17
Stenosis side
18
Cerebral protection device
Figure III. Pooled RRs of stroke for the different subgroups. Combined RRs were calculated with a fixed-effect meta-analysis, according to the Mantel-Haenszel method, or with a DerSimonian-Laird random-effects meta-analysis, where appropriate. Error bars correspond to the 95% CIs of individual RRs and pooled RR.
Touzé et al
Figure III (Continued).
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December 2009
Stroke
e708
Touzé et al
e709
e710
Table I.
Publication
Year
Stroke
December 2009
Characteristics of the Studies
Study
1992
Munari1
BERGAMO-NEURO-1
1996
Theron2
CAEN
Eckert3
HAMBURG-1
AR
Germany
1990–1995
Cohort
58
Diethrich4
PHOENIX
AR
USA
04/1993–09/1995
Cohort
110
Criado5
BALTIMORE
AR
USA
12/1997–03/2001
Cohort
33
Crawley6
LONDON-1
AR
UK
NA
RCT
28
Vozzi
ROSARIO
AR
Argentina
10/1995–03/1997
Cohort
22
Mendelsohn8
DURHAM-1
AR
USA
06/1996–10/1997
Cohort
28
1997
7
1998
1999
2000
Accrual Period
Design
AR
Italy
01/1986 – 01/1991
Cohort
40
AR & SG
France
1984–1995
Cohort
229
LEICESTER
AR
UK
06/1996–09/1999
RCT
Mathur10
LENNOX HILL, BIRMINGHAM
SG
USA
NA
Cohort
Teitelbaum11
LOS ANGELES
AR & SG
USA
NA
Cohort
21
Henry12
NANCY-1
AR
France
04/1995–04/1998
Cohort
163
Gross13
BERLIN
AR
Germany
02/1996–08/1998
Cohort
85
Sievert14
FRANKFURT-CVC
AR
Germany
NA
Cohort
71
Arakawa15
KURASHIKI
AR
Japan
NA
Cohort
6
Matushita16
OSAKA-TOKUSHUKAI-1
AR
Japan
05/1996–10/1998
Cohort
17
7
231
Reifart17
BAD SODEN
AR
Germany
11/1996–03/1999
Cohort
50
Parodi18
BUENOS-AERES
SG
Argentina-USA
09/1998–09/1999
Cohort
46
Qureshi
BUFFALO-1
AR & SG
USA
06/1996–12/1998
Cohort
111
Jacksch20
ESSEN
AR
Germany
NA
Cohort
47
Griewing21
HANNOVER
AR
Germany
05/1996–11/1997
Cohort
20
Gupta22
MILWAUKEE
AR & SG
USA
1996–1999
Cohort
100
Kaul23
NEW DELHI
AR
India
07/1997–06/1998
Cohort
14
Link24
REGENSBURG
AR
Germany
08/1999–02/2000
Cohort
23
Malek25
SAN FRANCISCO-MALEK
AR & SG
USA
07/1996–07/1999
Cohort
28
Yoon26
SEOUL-YONSEI
AR
Korea
05/1996–07/1999
Cohort
36
27
Shawl
TAKOMA PARK
AR & SG
USA
08/1995–06/1998
Cohort
170
Dangas28
WASHINGTON
AR
USA
NA
Cohort
133
Brown29
CAVATAS
AR
International
03/1992–07/1997
RCT
240
Dietz30
FRANKFURT-UNIVERSITY
AR
Germany
1997–2000
Cohort
43
31
Brooks
2002
Country
Naylor9
19
2001
Analysis
N
Patients
First Author
KENTUCKY-1
AR
USA
NA
RCT
53
Roubin32
AR & SG
USA
09/1994–09/1999
Cohort
528
Pappada33
MILAN-NEUROSURGERY
AR
Italy
01/1997–07/2000
Cohort
27
Baudier34
ODENSE
AR
Denmark
05/1993–10/1999
Cohort
54
Kirsch35
PERTH
AR & SG
Australia
11/1996–10/1999
Cohort
53
Orlandi36
PISA-1
AR
Italy
02/1998–07/2000
Cohort
38
Ahmadi37
VIENNA
SG
Austria
01/1997–11/2000
Cohort
303
Alberts 38
WALLSTENT
AR
USA
NA
RCT
107
39
BALTIMORE
AR & SG
USA
01/1994–06/1996
Cohort
132
Guimaraens40
Criado
BARCELONA-SANT CUGAT
AR
Spain
04/1994–04/2000
Cohort
159
Wang41
BEEJING-WANG
AR
China
NA
Cohort
16
Bonaldi42
BERGAMO-NEURO-2
AR
Italy
01/1997–10/2000
Cohort
70
43
Qureshi
BUFFALO-2
AR
USA
01/1999–12/1999
Cohort
70
Castriota44
COTIGNOLA
SG
Italy
NA
Cohort
275
Koch45
HAMBURG-2
AR & SG
Germany
07/1997–12/2001
Cohort
161
Milosevic46
LJUBLJANA
AR
Slovenia
NA
Cohort
17
47
LONDON-2
AR
UK
NA
RCT
Kaposzta
16
(Continued)
Touzé et al
Table I.
e711
Continued
Study
N Attempted
Procedures
Mean
Age, y
Male
(%)
Diabetes
(%)
Symptomatic
Carotid
Stenosis (%)
Prior
CEA/CAS
(%)
Prior
CAD
(%)
Prior
PAD
(%)
Contralateral
Occlusion
(%)
BERGAMO-NEURO-1
44
64
75
…
100
…
…
…
…
CAEN
229
…
…
…
…
22
…
…
…
HAMBURG-1
61
60
67
…
100
…
…
…
…
PHOENIX
117
72
79
17
28
17
54
34
…
BALTIMORE
33
…
63
24
73
…
30
…
…
LONDON-1
28
68
…
4
…
…
25
…
…
…
ROSARIO
24
69
73
…
45
…
32
…
DURHAM-1
19
69
61
28
78
6
…
…
…
LEICESTER
7
68
71
…
100
…
…
…
…
259
69
71
…
60
22
71
…
12
LOS ANGELES
26
63
59
…
68
…
…
…
…
NANCY-1
174
71
76
23
33
5
51
32
5
BERLIN
89
…
82
32
22
…
100
19
13
FRANKFURT-CVC
76
70
77
39
…
1
…
27
…
KURASHIKI
7
71
100
…
50
…
…
…
…
OSAKA-TOKUSHUKAI-1
18
…
…
…
…
…
…
…
…
BAD SODEN
50
68
86
34
…
12
84
…
…
BUENOS-AERES
46
67
76
28
39
15
41
…
7
BUFFALO-1
111
68
64
43
51
25
66
30
…
ESSEN
48
68
67
…
67
…
…
…
…
HANNOVER
20
65
75
…
80
…
71
…
55
MILWAUKEE
100
76
76
32
85
30
80
…
3
NEW DELHI
15
61
86
43
100
0
29
…
14
REGENSBURG
23
67
87
…
…
…
…
…
…
SAN FRANCISCO-MALEK
28
71
64
29
100
18
61
21
…
SEOUL-YONSEI
48
65
89
33
58
…
…
…
11
TAKOMA PARK
192
73
59
36
61
9
50
…
8
WASHINGTON
140
71
70
27
…
19
71
52
…
CAVATAS
240
67
69
14
97
…
39
24
10
FRANKFURT-UNIVERSITY
43
67
71
63
100
0
54
32
…
KENTUCKY-1
53
66
…
36
100
…
74
…
9
604
69
67
32
44
15
71
…
10
MILAN-NEUROSURGERY
27
…
…
…
…
…
…
…
…
ODENSE
53
64
69
9
98
…
24
19
…
PERTH
57
71
72
26
68
…
74
45
19
PISA-1
41
68
67
…
100
…
…
…
…
VIENNA
320
70
71
35
38
…
47
45
18
WALLSTENT
107
67
66
…
100
…
…
…
…
BALTIMORE
135
68
65
37
40
39
60
…
…
BARCELONA-SANT CUGAT
186
63
78
…
92
…
…
…
…
BEEJING-WANG
20
64
…
…
100
…
…
…
13
BERGAMO-NEURO-2
73
68
60
…
100
13
…
…
…
BUFFALO-2
70
70
54
37
39
11
53
…
…
COTIGNOLA
275
71
75
18
42
12
…
…
…
HAMBURG-2
167
66
72
…
77
…
…
…
…
LJUBLJANA
17
…
71
…
100
…
41
…
12
LONDON-2
16
67
81
25
100
…
…
…
…
(Continued)
e712
Table I.
Publication
Year
Stroke
December 2009
Continued
First Author
Study
Stankovic48
MILAN-COLUMBUS
Grego49
PADUA
Gray
50
N
Patients
01/1999 –12/2000
Cohort
100
09/1999–02/2001
Cohort
26
122
Accrual Period
AR
Italy
AR
Italy
SEATTLE
AR
USA
03/1996–09/1998
Cohort
STOCKTON
AR
USA
NA
Cohort
49
Kao52
TAPEI
AR & SG
Taiwan
04/1998–10/2000
Cohort
118
VIENNA
SG
Austria
03/2000–03/2001
Cohort
111
54
Moller-Hartmann
AACHEN
AR
Germany
12/1999–03/2002
Cohort
41
McKinlay55
CAReSS
AR
USA
04/2001–12/2002
Cohort
143
Becquemin56
CRETEIL
AR
France
01/1995–07/2002
Cohort
107
Gable57
DALLAS
AR
USA
05/1998–01/2002
Cohort
29
58
Rath
HYDERABAD
AR
India
01/2002–01/2003
Cohort
22
LEUVEN-1
AR & SG
Belgium
04/2000–04/2002
Cohort
51
Cernetti60
MIRANO
AR & SG
Italy
11/1999–03/2001
Cohort
100
Shevchenko61
MOSCOW-SHEVCHENKO
AR & SG
Russia
02/1998–09/2002
Cohort
39
Maleux59
62
OSAKA-POLICE
AR
Japan
NA
Cohort
41
Wholey63
PITTSBURGH
AR
USA
04/1994–12/2001
Cohort
550
Piske64
SAO PAULO-BENEFICIENCA
AR
Brazil
03/1998–06/2000
Cohort
42
Costa65
SAO PAULO-DO CORACAO
AR
Brazil
08/1996–04/2001
Cohort
86
Tan66
SHEFFIELD
SG
UK
10/1999–10/2002
Cohort
201
Cremonesi67
SIENNA-COTIGNOLA
SG
Italy
12/1999–06/2002
Cohort
442
Pucillo68
VALHALLA
AR
USA
2000–2003
Cohort
74
Causin69
VICENZA
AR & SG
Italy
06/1996–10/2002
Cohort
150
Dabrowski70
WARSAW
AR & SG
Poland
NA
Cohort
75
Zahn71
ALKK
SG
Germany
07/1996–03/2003
Cohort
1483
Koshimae
2004
Design
Country
Madyoon51
Ahmadi53
2003
Analysis
Garcia-Sanchez72
BADALONA
AR
Spain
01/2002–10/2002
Cohort
10
Sganzerla73
BERGAMO-CARDIO
AR & SG
Italy
NA
Cohort
94
Linfante74
BOSTON-BETH
AR
USA
06/2001–07/2002
Cohort
23
Clark75
BOSTON-ST ELIZABETH
AR & SG
USA
06/1995–01/2001
Cohort
98
Kobayashi76
CHIBA
AR
Japan
03/1998–04/2002
Cohort
30
Hobson77
CREST
AR & SG
USA
01/2000–03/2004
Cohort
749
Biasi78
ICAROS
AR & SG
International
07/2000–12/2001
Cohort
418
Brooks79
KENTUCKY-2
AR
USA
NA
RCT
43
Pieniazek80
KRAKOW
AR
Poland
01/2001–04/2006
Cohort
132
Sadato81
KYOTO
AR & SG
Japan
1999
Cohort
40
82
LEBANON
SG
USA
10/2000–09/2003
Cohort
69
Schmidt83
LEIPZIG
AR
Germany
03/2002–02/2003
Cohort
42
Henry84
NANCY-2
AR & SG
France
NA
Cohort
242
Choi85
NEWARK
AR
USA
09/1996–03/2004
Cohort
177
753
Powell
86
Reimers
REIMERS
SG
Germany-Italy
09/1999–09/2002
Cohort
Kihara87
RIO DE JANEIRO
AR & SG
Brazil
02/1998–03/2003
Cohort
79
Yadav88
SAPPHIRE
AR & SG
USA
08/2000–07/2002
RCT
159
McKevitt89
SHEFFIELD
AR & SG
UK
01/1993–09/2002
Cohort
328
90
Chang
Sztriha91
STANFORD SAN JOSE
AR
USA
08/2001–08/2003
Cohort
20
SZEGED
AR & SG
Hungary
01/2001–07/2003
Cohort
245
Sabeti92
VIENNA
SG
Austria
01/1997–12/2001
Cohort
471
Terada93
WAKAYAMA
AR & SG
Japan
08/1997–10/2003
Cohort
215
(Continued)
Touzé et al
Table I.
e713
Continued
Mean Age,
y
Male
(%)
Diabetes
(%)
Symptomatic
Carotid
Stenosis (%)
Prior
CEA/
CAS
(%)
Prior
CAD
(%)
Prior
PAD
(%)
Contralateral
Occlusion
(%)
Study
N Attempted
Procedures
MILAN-COLUMBUS
102
67
71
17
28
14
49
…
9
PADUA
26
72
85
58
46
27
62
15
4
SEATTLE
136
73
57
25
31
12
56
…
6
STOCKTON
49
74
61
…
…
18
…
…
6
TAPEI
128
73
89
34
75
…
75
5
11
VIENNA
111
70
67
35
30
…
41
50
…
AACHEN
43
…
…
…
…
…
…
…
…
CAReSS
143
71
60
29
31
…
66
45
…
CRETEIL
114
71
72
20
33
7
41
…
9
DALLAS
31
65
48
…
69
34
…
…
…
HYDERABAD
20
64
64
…
68
…
82
…
…
LEUVEN-1
54
73
72
…
61
12
48
…
6
…
MIRANO
104
71
71
22
26
4
62
…
MOSCOW-SHEVCHENKO
46
…
…
13
54
…
…
…
5
OSAKA-POLICE
41
71
83
…
46
…
…
…
…
PITTSBURGH
580
71
58
…
48
38
…
…
…
SAO PAULO-BENEFICIENCA
47
66
80
…
75
…
…
…
…
94
64
51
…
…
…
…
…
…
SHEFFIELD
204
68
68
18
85
…
47
…
…
SIENNA-COTIGNOLA
442
73
79
…
57
13
…
…
11
VALHALLA
78
…
…
…
25
46
…
…
…
VICENZA
156
68
77
…
100
23
…
…
20
WARSAW
77
65
65
27
76
…
63
…
12
1483
70
72
34
57
6
65
26
…
…
ALKK
BADALONA
10
66
80
40
100
…
…
20
BERGAMO-CARDIO
100
70
76
37
34
3
79
47
11
BOSTON-BETH
24
65
39
17
100
39
35
…
17
BOSTON-ST ELIZABETH
110
70
71
38
58
20
61
37
24
…
CHIBA
30
68
90
40
83
…
…
…
CREST
749
70
64
29
31
…
…
…
…
ICAROS
415
68
71
31
32
54
45
24
…
KENTUCKY-2
43
67
…
16
0
…
81
…
…
KRAKOW
137
63
73
30
62
2
69
57
20
KYOTO
43
71
83
…
40
…
…
…
…
LEBANON
74
72
82
39
38
18
…
…
26
LEIPZIG
42
70
81
43
31
…
74
…
5
NANCY-2
268
71
80
20
64
12
61
24
6
NEWARK
194
71
56
…
34
60
…
…
…
REIMERS
753
70
74
21
26
5
63
…
7
RIO DE JANEIRO
79
65
62
…
80
…
…
…
…
SAPPHIRE
159
73
67
25
30
23
86
…
24
SHEFFIELD
333
68
70
16
100
0
43
…
…
STANFORD SAN JOSE
21
73
80
10
62
19
28
…
0
SZEGED
260
65
57
…
48
4
…
…
13
VIENNA
471
72
81
31
37
…
42
48
9
WAKAYAMA
215
…
…
…
…
…
…
…
…
(Continued)
e714
Table I.
Publication
Year
2005
Stroke
December 2009
Continued
First Author
Analysis
Country
Accrual Period
Design
N
Patients
Zahn94
ALKK
SG
Germany
07/1996 – 07/2003
Cohort
729
Li95
BEIJING
AR & SG
China
10/1997–10/2004
Cohort
439
Bonaldi96
BERGAMO-VARESE
AR
Italy
07/2000–12/2003
Cohort
53
Hammer97
BRUSSELS
AR & SG
Belgium
11/2002–01/2005
Cohort
53
Eskandari98
CHICAGO
AR
USA
04/2001–02/2005
Cohort
168
Chen99
CHONGQING
AR
China
01/2003–06/2004
Cohort
28
174
100
Yen
CLEVELAND
SG
USA
01/2000–09/2002
Cohort
Lin101
DUSSELDORF-1
AR
Germany
10/2002–10/2004
Cohort
55
Nagata102
FUKUOKA
AR
Japan
12/1999–08/2004
Cohort
84
Lin103
HOUSTON
SG
USA
01/2002–03/2005
Cohort
182
68
104
Cohen
JERUSALEM
AR
Israël
10/2001–04/2005
Cohort
Dudek105
KRAKOW-DUDEK
AR
Poland
NA
Cohort
21
Bergeron106
MARSEILLE
AR
France
09/1991–09/2003
Cohort
193
Emanuelli107
MILAN-VASCULAR SURGERY
AR
Italy
1995
Cohort
113
MOSCOW-CARDIOVASC
AR & SG
Russia
NA
Cohort
20
OMAHA
AR
USA
12/2002–01/2005
Cohort
17
108
Bokeriia
Pipinos109
Cosottini110
PISA-2
AR
Italy
12/2003–10/2004
Cohort
52
Kadkhodayan111
SAINT-LOUIS-NEURO
AR & SG
USA
03/1996–12/2003
Cohort
131
SECURITY112
SECURITY
AR
USA
NA
Cohort
305
Roh113
SEOUL-SAMSUNG-1
AR
Korea
07/1998–02/2001
Cohort
22
Ackerstaff114
ST ANTONIUS
AR
Netherlands
12/1997–04/2004
Cohort
550
Vos115
ST ANTONIUS
SG
Netherlands
12/1997–12/2003
Cohort
509
327
116
Groschel
2006
Study
TUBINGEN
AR
Germany
04/1999–12/2004
Cohort
Kastrup117
TUBINGEN-JENA
SG
Germany
06/1999–08/2004
Cohort
299
Boltuch118
VIENNA
SG
Austria
01/1997–06/1905
Cohort
651
Gray119
ARCHeR
AR & SG
USA
05/2000–09/2003
Cohort
581
120
Kasirajan
White121
ATLANTA
AR & SG
USA
09/2000–09/2007
Cohort
127
BEACH
AR & SG
USA
02/2002–12/2003
Cohort
747
CABERNET122
CABERNET
AR
USA
02/2002–03/2004
Cohort
454
Katzen123
CASES-PMS
SG
USA
08/2003–10/2005
Cohort
1493
Criado124
CASES-PMS
SG
USA
08/2003–10/2005
Cohort
1493
Skelly125
CHICAGO-PHILADELPHIA
AR
USA
01/2002–10/2004
Cohort
97
Lanzer126
COSWIG
AR & SG
Germany
02/1999–05/2004
Cohort
143
Safian127
CREATE
AR & SG
USA
NA
Cohort
419
709
128
DENDERMONDE-BONHEIDEN
AR & SG
Belgium
01/2001–08/2005
Cohort
Hauth129
DORTMUND
AR
Germany
01/2000–12/2000
Cohort
91
McDonnell130
DUBLIN
AR & SG
Australia
NA
Cohort
98
Mas131
EVA-3S
AR & SG
France
11/2000–09/2005
RCT
261
46
Hart
132
FARMINGTON
AR
USA
12/2003–12/2005
Cohort
Rabe133
Park
FRANKFURT-CVC
AR
Germany
03/2001–10/2003
Cohort
56
Rubartelli134
GENOA
AR
Italy
NA
Cohort
31
Halabi135
HAIFA
AR & SG
Israël
02/1998–08/2005
Cohort
169
136
HONG-KONG
AR
China
01/1997–01/2004
Cohort
70
Lin137
HOUSTON
AR
USA
02/2002–08/2006
Cohort
354
Kawaguchi138
KASHIHARA
AR
Japan
01/2002–03/2005
Cohort
38
Maleux139
LEUVEN-2
AR
Belgium
01/2003–04/2005
Cohort
52
Wang
(Continued)
Touzé et al
Table I.
e715
Continued
Diabetes
(%)
Symptomatic
Carotid
Stenosis (%)
71
33
56
12
61
…
93
…
Study
N Attempted
Procedures
Mean
Age, y
Male
(%)
ALKK
729
70
BEIJING
478
68
Prior
CEA/CAS
(%)
Prior
CAD
(%)
Prior
PAD
(%)
Contralateral
Occlusion
(%)
67
27
…
…
…
9
BERGAMO-VARESE
53
68
66
…
72
8
…
…
…
BRUSSELS
53
72
75
40
34
…
…
…
8
CHICAGO
175
70
74
…
32
18
…
…
4
CHONGQING
28
…
68
…
100
…
…
…
…
…
CLEVELAND
193
…
…
…
36
…
…
…
DUSSELDORF-1
55
…
…
…
56
5
…
…
…
FUKUOKA
97
72
88
…
63
…
28
…
…
HOUSTON
200
71
95
50
25
…
72
…
…
JERUSALEM
73
72
62
45
100
18
…
…
12
KRAKOW-DUDEK
22
63
67
14
76
…
76
…
…
MARSEILLE
221
72
78
18
39
21
68
…
…
MILAN-VASCULAR SURGERY
113
70
81
27
49
12
35
…
14
MOSCOW-CARDIOVASC
22
60
80
10
35
5
80
…
…
OMAHA
17
65
88
41
47
29
…
…
…
PISA-2
52
73
81
35
44
…
37
…
…
SAINT-LOUIS-NEURO
142
64
63
27
48
47
36
24
…
SECURITY
305
75
64
31
21
21
…
…
9
SEOUL-SAMSUNG-1
22
62
100
…
82
…
…
…
36
ST ANTONIUS
550
70
70
…
34
10
…
…
…
ST ANTONIUS
509
71
71
…
33
10
…
…
…
TUBINGEN
327
69
74
26
56
…
25
17
13
TUBINGEN-JENA
299
69
73
25
57
…
25
17
14
VIENNA
651
72
68
36
30
6
42
46
10
ARCHeR
581
70
67
38
24
35
66
…
17
ATLANTA
127
71
…
…
28
34
…
…
…
BEACH
747
71
64
33
25
38
22
…
18
CABERNET
454
73
65
33
24
21
63
…
19
CASES-PMS
1493
73
63
35
22
24
…
…
12
CASES-PMS
1493
73
63
35
22
24
…
…
12
CHICAGO-PHILADELPHIA
101
70
55
32
40
29
61
…
…
COSWIG
143
69
70
49
26
6
44
20
20
CREATE
419
74
61
34
17
24
14
…
10
DENDERMONDE-BONHEIDEN
709
72
59
23
43
3
…
…
…
DORTMUND
94
67
75
46
70
11
67
58
…
DUBLIN
110
69
69
…
74
…
…
…
…
EVA-3S
260
74
72
22
100
0
…
14
5
…
FARMINGTON
46
69
50
41
22
…
76
…
FRANKFURT-CVC
58
68
70
21
41
…
54
…
2
GENOA
31
71
77
19
36
…
77
…
3
HAIFA
185
71
63
40
…
50
76
31
…
HONG-KONG
70
…
83
43
63
8
40
…
9
HOUSTON
380
71
96
57
24
…
76
…
…
KASHIHARA
38
70
82
…
100
…
…
…
21
LEUVEN-2
53
73
77
…
29
…
…
…
…
(Continued)
e716
Table I.
Publication
Year
Stroke
December 2009
Continued
Study
Kypta140
LINZ
SG
Austria
12/1997–NA
Cohort
718
Hofmann141
LINZ
AR & SG
Austria
12/1997–05/2005
Cohort
606
Alexandrescu142
MARCHE-EN-FAMENNE
AR
Belgium
02/2002–NA
Cohort
26
Hill143
MAVERIC
AR
International
11/2001–12/2002
Cohort
51
Dalainas144
MILAN-SAN DONATO
AR
Italy
02/2001–10/2004
RCT
100
Mussack145
MUNCHEN-MUSSAK
AR
Germany
NA
Cohort
14
MUNCHEN-POPPERT
AR
Germany
NA
Cohort
41
NY, PRESBYTERIAN
AR
USA
01/1997–01/2005
Cohort
148
Iihara148
OSAKA
AR & SG
Japan
09/1998–08/2004
Cohort
92
Verzini149
PERUGIA
AR & SG
Italy
05/2001–04/2006
Cohort
570
Tinoco150
RIO DE JANEIRO
AR
Brazil
01/2004–01/2006
Cohort
40
Zindler151
ROTTERDAM
AR
Netherlands
01/1999–01/2004
Cohort
98
Marine152
SAINT-LOUIS-VASCULAR
AR
USA
09/2003–04/2005
Cohort
93
Carvalho153
SAO PAULO-SAO JOACHIM
AR & SG
Brazil
03/2000–06/2004
Cohort
113
146
Poppert
Chaer147
154
Country
Accrual Period
Design
SEOUL-YONGON DONG
AR
Korea
02/2004–12/2005
Cohort
72
Gonzalez-Marcos155
SEVILLE
SG
Spain
NA
Cohort
607
Setacci156
SIENNA-COTIGNOLA
AR & SG
Italy
12/2000–09/2005
Cohort
1053
Setacci157
SIENNA-RAVENNA
SG
Italy
12/2000–03/2006
Cohort
1729
Ringleb158
SPACE
AR & SG
Europe
03/2001–02/2006
RCT
567
Wu159
TAIWAN-KAOSIUNG
AR
China
03/2005–07/2005
Cohort
13
Kassaian160
TEHERAN
AR
Iran
12/2003–10/2004
Cohort
30
Ling161
TESCAS-C
AR
China
NA
RCT
166
Kwon
162
Gupta
2007
Analysis
N
Patients
First Author
TRIVANDRUM
AR & SG
India
01/1995–06/2006
Cohort
47
Asakura163
TSU CITY
AR & SG
Japan
2002–2004
Cohort
57
Reiter164
VIENNA
AR & SG
Austria
01/1997–06/2005
Cohort
698
Mehta165
ALKK
SG
Germany
07/1996–03/2006
Cohort
3070
Zahn166
ALKK
AR & SG
Germany
07/1996–12/2005
Cohort
2878
Matas167
BARCELONA-HEBRON
AR
Spain
01/2005–06/2006
Cohort
62
Faggioli168
BOLOGNA
AR & SG
Italy
01/2005–03/2007
Cohort
298
Bosiers169
BOSIERS-MULTI
SG
Italy-Belgium
NA
Cohort
3179
170
Ascher
BROOKLYN
AR
USA
NA
Cohort
34
Parodi171
BUENOS-AERES
AR
Argentina-USA
09/1999–12/2003
Cohort
200
Gray172
CAPTURE
AR
USA
10/2004–03/2006
Cohort
3500
Gray173
CAPTURE
SG
USA
10/2004–03/2006
Cohort
3500
174
CAPTURE
SG
USA
10/2004–03/2006
Cohort
3500
Katzen175
CASES-PMS
SG
USA
08/2003–10/2005
Cohort
1493
Gurm176
CLEVELAND
SG
USA
02/1998–08/2005
Cohort
833
Rajagopal177
CLEVELAND
SG
USA
02/1998–08/2005
Cohort
915
Fairman
178
Huppert
DARMSTADT
AR
Germany
NA
Cohort
120
Iyer179
DENDERMONDE-SIENACOTTIGNOLA
SG
Belgium-Italy
01/1997–01/2006
Cohort
3260
Pinter180
DUSSELDORF-2
AR
Germany
03/2006–12/2006
Cohort
20
EXACT181
EXACT
AR
USA
NA
Cohort
1500
CAPTURE-2181
CAPTURE-2
AR
USA
NA
Cohort
597
Wijtenburg182
HAINE-ST PAUL
AR
Belgium
2003–2005
Cohort
Grunwald183
HOMBURG
AR & SG
Germany
NA
Cohort
90
Younis184
HOUSTON ST LUKE
AR & SG
USA
07/1995–09/2004
Cohort
363
(Continued)
Table I.
Touzé et al
Study
N Attempted
Procedures
Mean
Age, y
Male
(%)
Diabetes
(%)
LINZ
742
…
…
LINZ
628
72
65
e717
Continued
Symptomatic
Carotid
Stenosis (%)
Prior
CEA/CAS
(%)
Prior
CAD
(%)
Prior
PAD
(%)
Contralateral
Occlusion
(%)
…
35
…
…
…
…
29
35
8
45
17
10
31
MARCHE-EN-FAMENNE
29
74
65
42
88
…
…
…
MAVERIC
52
69
84
24
…
29
…
…
28
MILAN-SAN DONATO
100
65
60
17
23
…
50
35
…
MUNCHEN-MUSSAK
14
70
79
…
64
…
…
…
…
…
MUNCHEN-POPPERT
41
71
66
…
44
…
…
…
NY, PRESBYTERIAN
148
75
61
26
…
18
64
…
10
OSAKA
92
71
90
40
36
…
38
45
…
PERUGIA
627
72
70
31
22
15
…
19
8
RIO DE JANEIRO
40
67
55
20
30
…
25
…
0
ROTTERDAM
98
68
89
…
100
…
…
…
…
SAINT-LOUIS-VASCULAR
93
70
63
30
0
28
58
38
…
SAO PAULO-SAO JOACHIM
130
74
74
44
45
15
70
…
12
SEOUL-YONGON DONG
78
70
81
…
47
…
25
…
10
SEVILLE
607
…
78
…
100
…
…
…
…
SIENNA-COTIGNOLA
1222
72
86
…
65
…
…
…
9
SIENNA-RAVENNA
1981
…
…
29
…
…
…
…
…
SPACE
567
68
72
26
100
0
21
…
7
TAIWAN-KAOSIUNG
13
72
92
39
100
…
…
…
…
TEHERAN
30
66
60
47
26
…
100
…
…
TESCAS-C
166
63
…
…
…
…
…
…
…
TRIVANDRUM
49
61
74
…
96
…
45
…
6
TSU CITY
60
69
92
…
50
…
…
…
…
VIENNA
698
73
69
36
30
…
…
…
10
ALKK
3070
71
73
32
49
…
67
25
…
ALKK
2878
71
73
32
49
9
69
26
…
BARCELONA-HEBRON
62
77
84
34
39
3
61
…
11
BOLOGNA
298
75
63
…
…
…
…
…
6
BOSIERS-MULTI
3179
72
67
26
41
6
…
…
…
BROOKLYN
35
73
71
40
34
37
51
…
…
BUENOS-AERES
200
70
73
19
52
9
27
…
6
CAPTURE
3545
73
61
35
14
…
67
36
8
CAPTURE
3545
73
61
35
14
…
67
36
8
CAPTURE
3545
73
61
35
14
…
67
36
8
CASES-PMS
1493
73
63
35
22
24
…
…
12
CLEVELAND
833
71
65
37
38
23
79
36
14
CLEVELAND
915
…
…
…
…
…
…
…
…
DARMSTADT
120
…
…
…
67
…
…
…
…
DENDERMONDE-SIENA-COTTIGNOLA
3260
…
67
26
41
7
…
…
…
…
DUSSELDORF-2
20
72
70
30
35
…
45
…
EXACT
1500
…
…
…
10
…
…
…
…
CAPTURE-2
597
…
…
…
12
…
…
…
…
HAINE-ST PAUL
19
64
67
22
28
22
28
…
…
HOMBURG
90
66
66
…
17
…
…
…
…
HOUSTON ST LUKE
399
71
68
14
33
9
89
87
…
(Continued)
e718
Table I.
Publication
Year
Stroke
December 2009
Continued
First Author
Analysis
Country
Accrual Period
Design
N
Patients
Lojik185
HRADEK
AR
Czech Republic
09/2001– 08/2006
Cohort
204
Aydiner186
ISTAMBUL
AR & SG
Turkey
03/2002–12/2004
Cohort
26
KAOHSIUNG
AR
Taiwan
NA
Cohort
77
LINZ
AR & SG
Austria
08/1999–06/2006
Cohort
77
Timler189
LODZ
AR
Poland
01/2004–08/2006
Cohort
27
Brightwell190
LONDON-SURGERY
AR
UK
04/2005–06/2006
Cohort
24
Montorsi191
MILAN
AR
Italy
NA
Cohort
306
Spes192
MUNCHEN-STADTISCHES
AR
Germany
11/1999–05/2006
Cohort
371
Henry193
NANCY-3
AR
France
NA
Cohort
34
Lam194
NY, PRESBYTERIAN
SG
USA
02/2003–08/2005
Cohort
133
Tsai195
ORANGE
AR
USA
NA
Cohort
105
Kawarada196
OSAKA-TOKUSHUKAI-2
AR
Japan
12/1996–05/2006
Cohort
51
Veselka197
PRAGUE
AR
Czech Republic
09/2005–01/2007
Cohort
83
Folmar198
RALEIGH
AR
USA
01/2005–08/2006
Cohort
42
Fanelli199
ROMA-FANELLI
AR
Italy
02/2000–NA
Cohort
230
Gandini200
ROMA-GANDINI
AR
Italy
04/1999–NA
Cohort
612
Gossetti201
ROMA-SAPIENZA
AR
Italy
01/2005–01/2006
Cohort
50
Kadkhodayan202
SAINT-LOUIS-NEURO
SG
USA
03/1996–03/2005
Cohort
153
Wu
187
Topakian188
2008
Study
Rapp203
SAN FRANCISCO-RAPP
AR
USA
02/2005–08/2006
Cohort
48
Sanchez204
SG
Brazil
01/2002–01/2005
Cohort
230
Suk205
SEOUL-SAMSUNG-2
AR & SG
Korea
05/2002–10/2005
Cohort
70
Maynar206
TENERIFE
AR
Spain
06/2002–10/2004
Cohort
87
Saratzis207
THESSALONIKI
AR
Greece
05/2003–04/2005
Cohort
232
Criado208
TOLEDO
AR
Spain
03/2003–07/2005
Cohort
97
Hoffman209
BACASS
AR
Switzerland
11/1998–02/2002
RCT
10
Silvestro210
BRESCIA
AR & SG
Italy
2000–2005
Cohort
138
CAPTURE-2181,211
CAPTURE 2
AR & SG
USA
NA
Cohort
2070
Uflacker212
CHARLESTON
AR
USA
01/2005–09/2007
Cohort
100
Cremonesi213
CREMONESI (MULTI)
AR
Italy-Germany
10/2006–03/2007
Cohort
124
Priban214
CSEKE BUDEJOVICE
AR
Czech Republic
01/2003–10/2006
Cohort
90
86
215
Ozturk
IZMIR
AR
Turkey
06/2003–09/2007
Cohort
Uddin216
KARACHI
AR
Pakistan
09/2002–12/2005
Cohort
17
Buszman217
KATOWICE
AR & SG
Poland
06/1997–03/2005
Cohort
223
Yuo218
LEBANON
AR
USA
10/2000–08/2006
Cohort
179
219
LIMOGES
AR
France
10/2003–01/2006
Cohort
50
Bianchi220
LOMA LINDA
AR
USA
10/2003–02/2006
Cohort
50
Jackson221
PHILADELPHIA
AR & SG
USA
07/2003–12/2005
Cohort
170
Barbato222
PITTSBURGH
SG
USA
12/2003–01/2006
Cohort
35
223
Ghorab
Sayeed
PITTSBURGH
SG
USA
06/1996–06/2005
Cohort
421
Theiss224
PROCAS
SG
Europe
07/1999–06/2005
Cohort
5341
Sanchez225
AR
Brazil
01/2002–01/2005
Cohort
230
Martinez-Fernandez226
SEVILLE
AR
Spain
1992
Cohort
359
227
SHIRAZ
AR
Iran
04/2005–03/2003
Cohort
42
Stingele228
SPACE
SG
Europe
03/2001–02/2006
RCT
567
Groschel229
TUBINGEN-GOTTINGEN
SG
Germany
01/2000–03/2007
Cohort
320
Kastrup230
TUBINGEN-GOTTINGEN
SG
Germany
04/1999–12/2006
Cohort
243
UDINE
AR & SG
Italy
NA
Cohort
Kojuri
231
Piccoli
415
(Continued)
Table I.
Touzé et al
Study
N Attempted
Procedures
Mean
Age, y
Male
(%)
Diabetes
(%)
Symptomatic
Carotid
Stenosis (%)
HRADEK
212
65
67
…
ISTAMBUL
28
70
72
42
KAOHSIUNG
83
…
…
LINZ
77
67
68
e719
Continued
Prior
CEA/CAS
(%)
Prior
CAD
(%)
Prior
PAD
(%)
Contralateral
Occlusion
(%)
47
12
…
…
63
50
…
73
11
8
…
…
…
…
…
…
34
100
0
…
…
…
LODZ
27
…
…
…
96
…
…
…
…
LONDON-SURGERY
24
63
83
29
42
…
79
…
…
MILAN
306
70
…
…
27
…
…
…
…
MUNCHEN-STADTISCHES
371
71
71
36
31
…
71
26
…
NANCY-3
35
71
68
41
29
…
…
…
…
NY, PRESBYTERIAN
135
65
65
…
49
22
…
…
20
…
ORANGE
105
…
…
…
…
…
…
…
OSAKA-TOKUSHUKAI-2
53
70
78
56
54
…
66
32
10
PRAGUE
100
68
54
47
…
…
69
…
…
RALEIGH
42
71
62
45
21
2
76
31
2
ROMA-FANELLI
230
…
…
…
…
21
…
…
…
ROMA-GANDINI
665
…
…
…
52
…
…
…
…
ROMA-SAPIENZA
50
…
…
…
…
…
…
…
…
SAINT-LOUIS-NEURO
153
66
63
27
50
47
36
20
…
SAN FRANCISCO-RAPP
54
71
100
…
48
…
…
…
…
268
68
…
…
74
7
…
…
…
SEOUL-SAMSUNG-2
71
67
84
…
66
…
…
…
…
TENERIFE
100
71
82
25
58
…
59
…
…
THESSALONIKI
232
76
65
33
71
4
33
28
…
TOLEDO
103
72
80
21
36
…
34
…
…
BACASS
10
69
80
30
100
…
20
…
10
BRESCIA
154
72
63
33
46
…
55
…
6
CAPTURE 2
2070
73
61
…
…
…
…
…
…
CHARLESTON
100
70
80
…
72
36
…
…
…
CREMONESI (MULTI)
124
72
71
34
24
…
…
…
…
CSEKE BUDEJOVICE
90
71
69
31
70
12
44
…
…
IZMIR
87
68
78
30
81
…
…
…
…
KARACHI
18
…
82
…
88
…
…
…
…
KATOWICE
256
65
68
26
38
…
93
25
…
LEBANON
196
72
79
38
39
21
…
…
…
LIMOGES
50
70
76
26
62
…
…
…
…
LOMA LINDA
50
70
96
44
28
12
46
20
…
PHILADELPHIA
215
71
53
…
41
29
…
…
17
PITTSBURGH
36
76
64
28
17
…
61
…
…
PITTSBURGH
429
72
62
…
35
32
…
…
14
PROCAS
5341
70
71
…
55
8
…
…
…
268
68
…
…
74
7
…
…
…
SEVILLE
359
63
78
40
87
…
…
29
…
SHIRAZ
42
67
71
24
…
…
100
…
…
SPACE
567
68
72
26
100
0
21
…
7
TUBINGEN-GOTTINGEN
320
69
70
28
100
…
28
…
…
TUBINGEN-GOTTINGEN
243
68
75
28
55
…
22
…
17
UDINE
415
…
…
…
60
…
…
…
…
(Continued)
e720
Table I.
Publication
Year
Stroke
December 2009
Continued
Design
N
Patients
01/2002– 07/2007
Cohort
179
07/1999–03/2003
Cohort
56
Cohort
99
First Author
Study
Analysis
Country
De Gregorio232
ZARAGOZA
AR & SG
Spain
Kimiagar233
ZERIFIN
AR
Israël
ZURICH
AR
Switzerland
07/2003–11/2006
234
Roffi
Accrual Period
AR, Absolute Risk; SG, Subgroups; NA, Not Available; RCT, Randomised Clinical Trial.
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Radiology 1996;201:627–36.
3. Eckert B, Zanella FE, Thie A, Steinmetz J, Zeumer H. Angioplasty of the internal carotid artery: Results, complications and follow-up in 61 cases.
Cerebrovascular Diseases 1996;6:97–105.
4. Diethrich EB, Ndiaye M, Reid DB. Stenting in the carotid artery: initial experience in 110 patients. J Endovasc Surg 1996;3:42– 62.
5. Criado FJ, Wellons E, Clark NS. Evolving indications for and early results of carotid artery stenting. Am J Surg 1997;174:111– 4.
6. Crawley F, Clifton A, Buckenham T, Loosemore T, Taylor RS, Brown MM. Comparison of hemodynamic cerebral ischemia and microembolic signals detected
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1998;28:326 –34.
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13. Gross CM, Kramer J, Uhlich F, et al. Treatment of carotid artery stenosis by elective stent placement instead of carotid endarterectomy in patients with severe
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15. Arakawa Y, Ishii A, Ueno Y, et al. 关Self-expanding stent (Wallstent) supported angioplasty for carotid artery stenosis兴. No Shinkei Geka 1999;27:817–23.
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17. Reifart N. 关Carotid percutaneous transluminal angioplasty in cardiological patients with increased surgical risk兴. Z Kardiol 2000;89 Suppl 8:27–31.
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2000;32:1127–36.
19. Qureshi AI, Luft AR, Janardhan V, et al. Identification of patients at risk for periprocedural neurological deficits associated with carotid angioplasty and stenting.
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20. Jacksch R, Schiele TM, Knobloch W, Niehues R, Hauser ER, Massalha K. 关Carotid stenting with the new slotted tube stent—prospective multicenter study.
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2000;40:813–20.
25. Malek AM, Higashida RT, Phatouros CC, et al. Stent angioplasty for cervical carotid artery stenosis in high-risk symptomatic NASCET-ineligible patients. Stroke
2000;31:3029 –33.
26. Yoon YS, Shim WH, Kim SM, Park KJ, Cho SY. Carotid artery stenting in patients with symptomatic coronary artery disease. Yonsei Med J 2000;41:89 –97.
27. Shawl F, Kadro W, Domanski MJ, et al. Safety and efficacy of elective carotid artery stenting in high-risk patients. J Am Coll Cardiol 2000;35:1721– 8.
28. Dangas G, Laird JR Jr, Satler LF, et al. Postprocedural hypotension after carotid artery stent placement: predictors and short- and long-term clinical outcomes.
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29. Endovascular vs surgical treatment in patients with carotid stenosis in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS): a
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30. Dietz A, Berkefeld J, Theron JG, et al. Endovascular treatment of symptomatic carotid stenosis using stent placement: long-term follow-up of patients with
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31. Brooks WH, McClure RR, Jones MR, Coleman TC, Breathitt L. Carotid angioplasty and stenting vs carotid endarterectomy: randomized trial in a community
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32. Roubin GS, New G, Iyer SS, et al. Immediate and late clinical outcomes of carotid artery stenting in patients with symptomatic and asymptomatic carotid artery
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33. Pappada G, Marina R, Fiori L, et al. Stenting of atherosclerotic stenoses of the extracranial carotid artery. Acta Neurochir (Wien) 2001;143:1005–11.
34. Baudier JF, Licht PB, Roder O, Andersen PE. Endovascular treatment of severe symptomatic stenosis of the internal carotid artery: early and late outcome.
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53 patients. Radiology 2001;220:737– 44.
(Continued)
Table I.
Touzé et al
Study
N Attempted
Procedures
Mean
Age, y
Male
(%)
Diabetes
(%)
ZARAGOZA
203
66
86
ZERIFIN
60
69
80
ZURICH
100
68
82
e721
Continued
Symptomatic
Carotid
Stenosis (%)
Prior
CEA/CAS
(%)
Prior
CAD
(%)
Prior
PAD
(%)
Contralateral
Occlusion
(%)
…
94
…
…
…
…
50
100
20
77
39
16
24
25
8
…
…
11
36. Orlandi G, Fanucchi S, Fioretti C, et al. Characteristics of cerebral microembolism during carotid stenting and angioplasty alone. Arch Neurol 2001;58:1410 –3.
37. Ahmadi R, Willfort A, Lang W, et al. Carotid artery stenting: effect of learning curve and intermediate-term morphological outcome. J Endovasc Ther
2001;8:539 – 46.
38. Alberts MJ. Results of the multicenter prospective randomized trail of carotid artery stenting vs carotid endarterectomy. Stroke 2001;32:325.
39. Criado FJ, Lingelbach JM, Ledesma DF, Lucas PR. Carotid artery stenting in a vascular surgery practice. J Vasc Surg 2002;35:430 – 4.
40. Guimaraens L, Sola MT, Matali A, et al. Carotid angioplasty with cerebral protection and stenting: report of 164 patients (194 carotid percutaneous transluminal
angioplasties). Cerebrovasc Dis 2002;13:114 –9.
41. Wang D, Sheng A, Gong T, et al. 关Initial application of brain protection device in dilatation and stenting of carotid and vertebral artery stenosis兴. Zhonghua
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42. Bonaldi G. Angioplasty and stenting of the cervical carotid bifurcation: report of a 4-year series. Neuroradiology 2002;44:164 –74.
43. Qureshi AI, Suri MF, Ali Z, et al. Carotid angioplasty and stent placement: a prospective analysis of perioperative complications and impact of intravenously
administered abciximab. Neurosurgery 2002;50:466 –73.
44. Castriota F, Cremonesi A, Manetti R, et al. Impact of cerebral protection devices on early outcome of carotid stenting. J Endovasc Ther 2002;9:786 –92.
45. Koch C, Kucinski T, Eckert B, Wittkugel O, Rother J, Zeumer H. 关Endovascular therapy of high-degree stenoses of the neck vessels-stent-supported
percutaneous angioplasty of the carotid artery without cerebral protection兴. Rofo 2002;174:1506 –10.
46. Milosevic Z, Zvan B, Zaletel M, Surlan M. Carotid angioplasty with cerebral protection. Acta Clin Croat 2002;41:15–21.
47. Kaposzta Z, Clifton A, Molloy J, Martin JF, Markus HS. S-nitrosoglutathione reduces asymptomatic embolization after carotid angioplasty. Circulation
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48. Stankovic G, Liistro F, Moshiri S, et al. Carotid artery stenting in the first 100 consecutive patients: results and follow up. Heart 2002;88:381– 6.
49. Grego F, Frigatti P, Amista P et al. Prospective comparative study of two cerebral protection devices in carotid angioplasty and stenting. J Cardiovasc Surg
(Torino) 2002;43:391–7.
50. Gray WA, White HJ Jr, Barrett DM, Chandran G, Turner R, Reisman M. Carotid stenting and endarterectomy: a clinical and cost comparison of revascularization
strategies. Stroke 2002;33:1063–70.
51. Madyoon H, Braunstein E, Callcott F, et al. Unprotected carotid artery stenting compared to carotid endarterectomy in a community setting. J Endovasc Ther
2002;9:803–9.
52. Kao HL, Lin LY, Lu CJ, Jeng JS, Yip PK, Lee YT. Long-term results of elective stenting for severe carotid artery stenosis in Taiwan. Cardiology 2002;97:89 –93.
53. Ahmadi R, Schillinger M, Lang W, Mlekusch W, Sabeti S, Minar E. Carotid artery stenting in older patients: is age a risk factor for poor outcome? J Endovasc
Ther 2002;9:559 – 65.
54. Moller-Hartmann W, Mull M, Krings T, Klotzsch C, Gunther RW, Thron A. Carotid Artery Stenting with and without Cerebral Protection: Report of 43 Procedures.
Rivista di Neuroradiologia 2003;16:1327–29.
55. McKinlay S, White RA, Diethrich EB, et al. Carotid Revascularization Using Endarterectomy or Stenting Systems (CARESS): Phase I Clinical Trial. J Endovasc
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56. Becquemin JP, Ben El KH, Desgranges P, Kobeiter H. Carotid stenting vs carotid surgery: a prospective cohort study. J Endovasc Ther 2003;10:687–94.
57. Gable DR, Bergamini T, Garrett WV, et al. Intermediate follow-up of carotid artery stent placement. Am J Surg 2003;185:183–7.
58. Rath PC, Lakshmi G, Agarwala M, et al. Carotid artery stenting with filter protection. Indian Heart J 2003;55:241– 4.
59. Maleux G, Bernaerts P, Thijs V, et al. Extracranial carotid artery stenting in surgically high-risk patients using the Carotid Wallstent endoprosthesis: midterm
clinical and ultrasound follow-up results. Cardiovasc Intervent Radiol 2003;26:340 – 6.
60. Cernetti C, Reimers B, Picciolo A, et al. Carotid artery stenting with cerebral protection in 100 consecutive patients: immediate and two-year follow-up results.
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61. Shevchenko I, Krotovskii GS, Shcherbiuk AN, et al. 关Comparative assessment of the results of open carotid endarterectomy and carotid aftery stenting兴.
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62. Koshimae N, Morimoto T, Nagata K. Stenting of extracranial carotid artery stenosis. Intervent Neuroradiol 2003;9 (suppl 1):137– 41.
63. Wholey MH, Wholey MH, Eles G, et al. Evaluation of glycoprotein IIb/IIIa inhibitors in carotid angioplasty and stenting. J Endovasc Ther 2003;10:33– 41.
64. Piske RL, Ferreira MS, Campos CMS, et al. The cerebral protection technique in angioplasty plus stenting of carotid: An effective procedure against cerebral
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65. Costa JR Jr, Cano MN, Oliveira DC, et al. Percutaneous implantation of endoprostheses in the carotid arteries. Arq Bras Cardiol 2003;80:77– 6.
66. Tan KT, Cleveland TJ, Berczi V, McKevitt FM, Venables GS, Gaines PA. Timing and frequency of complications after carotid artery stenting: what is the optimal
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68. Pucillo AL, Mateo RB, Aronow WS. Effect of carotid angioplasty-stenting on short-term mortality and stroke. Heart Dis 2003;5:378 –9.
69. Causin F, Castellan L, Iannucci G, et al. Perioperative and immediate outcome of endovascular treatment of extracranial carotid artery steno-occlusive disease.
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70. Dabrowski M, Bielecki D, Golebiewski P, Kwiecinski H. Percutaneous internal carotid artery angioplasty with stenting: early and long-term results. Kardiol Pol
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(Continued)
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75. Clark DJ, Lessio S, O’Donoghue M, Schainfeld R, Rosenfield K. Safety and utility of intravascular ultrasound-guided carotid artery stenting. Catheter Cardiovasc
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76. Kobayashi E, Uchino Y, Ono J, Yamaura A. Treatment outcome of carotid stenting and CEA in the same period. Intervent Neuroradiol 2004;10:93– 6.
77. Hobson Ii RW, Howard VJ, Roubin GS, et al. Carotid artery stenting is associated with increased complications in octogenarians: 30-Day stroke and death
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78. Biasi GM, Froio A, Diethrich EB, et al. Carotid plaque echolucency increases the risk of stroke in carotid stenting: the Imaging in Carotid Angioplasty and Risk
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79. Brooks WH, McClure RR, Jones MR, Coleman TL, Breathitt L. Carotid angioplasty and stenting vs carotid endarterectomy for treatment of asymptomatic carotid
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80. Pieniazek P, Kablak-Ziembicka A, Przewlocki T, et al. Carotid artery stenting with proximal or distal brain protection: Early outcome. Kardiologia Polska
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81. Sadato A, Satow T, Ishii A, Ohta T, Hashimoto N. Use of a large angioplasty balloon for predilation is a risk factor for embolic complications in protected carotid
stenting. Neurol Med Chir (Tokyo) 2004;44:337– 42.
82. Powell RJ, Schermerhorn M, Nolan B, et al. Early results of carotid stent placement for treatment of extracranial carotid bifurcation occlusive disease. J Vasc
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83. Schmidt A, Diederich KW, Scheinert S, et al. Effect of two different neuroprotection systems on microembolization during carotid artery stenting. J Am Coll
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84. Henry M, Polydorou A, Henry I, Polydorou A, Hugel M. Carotid angioplasty under cerebral protection with the PercuSurge GuardWire System. Catheter
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85. Choi HM, Hobson RW, Goldstein J, et al. Technical challenges in a program of carotid artery stenting. J Vasc Surg 2004;40:746 –51.
86. Reimers B, Schluter M, Castriota F, et al. Routine use of cerebral protection during carotid artery stenting: Results of a multicenter registry of 753 patients.
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87. Kihara EN, Andrioli MS, Zukerman E, et al. Endovascular treatment of carotid artery stenosis: retrospective study of 79 patients treated with stenting and
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92. Sabeti S, Schillinger M, Mlekusch W, et al. Contralateral high-grade carotid artery stenosis or occlusion is not associated with increased risk for poor
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94. Zahn R, Ischinger T, Mark B, et al. Embolic protection devices for carotid artery stenting: is there a difference between filter and distal occlusive devices?
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95. Li SM, Li D, Ling F, Miao ZR, Wang ML. Carotid artery stenting: Experience of a single institute in China. Intervent Neuroradiol 2005;11:205–212.
96. Bonaldi G, Aiazzi L, Baruzzi F, et al. Angioplasty and stenting of the cervical carotid bifurcation under filter protection: a prospective study in a series of 53
patients. J Neuroradiol 2005;32:109 –17.
97. Hammer FD, Lacroix V, Duprez T, et al. Cerebral microembolization after protected carotid artery stenting in surgical high-risk patients: results of a 2-year
prospective study. J Vasc Surg 2005;42:847–53.
98. Eskandari MK, Longo GM, Matsumura JS, et al. Carotid stenting done exclusively by vascular surgeons: first 175 cases. Ann Surg 2005;242:431– 6.
99. Chen KN, Chi LX, Shi SG, Fan WH. Endovascular stenting of carotid stenosis under cerebral protection device: Short-term follow-up of the incidence of cerebral
ischemia in 28 patients. Chinese Journal of Clinical Rehabilitation 2005;9:14 –5.
100. Yen MH, Lee DS, Kapadia S, et al. Symptomatic patients have similar outcomes compared with asymptomatic patients after carotid artery stenting with emboli
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101. Lin JC, Kolvenbach RR, Pinter L. Protected carotid artery stenting and angioplasty via transfemoral vs transcervical approaches. Vasc Endovascular Surg
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102. Nagata S, Kazekawa K, Aikawa H, et al. Hemodynamic stability under general anesthesia in carotid artery stenting. Radiat Med 2005;23:427–31.
103. Lin PH, Bush RL, Peden EK, et al. Carotid artery stenting with neuroprotection: assessing the learning curve and treatment outcome. Am J Surg
2005;190:850 –7.
104. Cohen JE, Umansky F, Rajz G, Ben-Hur T. Protected stent-assisted carotid angioplasty in symptomatic high-risk NASCET-ineligible patients. Neurol Res
2005;27 Suppl 1:S59 –S63.
105. Dudek D, Bartus S, Rakowski T, Zmudka K, Dubiel JS. MO.MA - A new cerebral stroke protection system during carotid artery stenting. Kardiologia Polska
2005;62:565–70.
106. Bergeron P, Roux M, Khanoyan P, Douillez V, Bras J, Gay J. Long-term results of carotid stenting are competitive with surgery. J Vasc Surg 2005;41:213–21.
107. Emanuelli G, Marina R, Bizzi U, Perona F, Pecora N. Endovascular therapy vs surgery in carotid stenosis: Personal experience. Italian Journal of Vascular and
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108. Bokeriia LA, Alekian BG, Buziashvili I, et al. 关Short- and long-term effects of internal carotid arteries stenting in high-risk patients兴. Zh Nevrol Psikhiatr Im
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109. Pipinos II, Johanning JM, Pham CN, Soundararajan K, Lynch TG. Transcervical approach with protective flow reversal for carotid angioplasty and stenting.
J Endovasc Ther 2005;12:446 –53.
110. Cosottini M, Michelassi MC, Puglioli M, et al. Silent cerebral ischemia detected with diffusion-weighted imaging in patients treated with protected and
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e723
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113. Roh HG, Byun HS, Ryoo JW, et al. Prospective analysis of cerebral infarction after carotid endarterectomy and carotid artery stent placement by using
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114. Ackerstaff RG, Suttorp MJ, Van Den Berg JC, et al. Prediction of early cerebral outcome by transcranial Doppler monitoring in carotid bifurcation angioplasty
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115. Vos JA, Van Den Berg JC, Ernst SM, et al. Carotid angioplasty and stent placement: comparison of transcranial Doppler US data and clinical outcome with
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116. Groschel K, Ernemann U, Riecker A, Schmidt F, Terborg C, Kastrup A. Incidence and risk factors for medical complications after carotid artery stenting.
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117. Kastrup A, Groschel K, Schulz JB, Nagele T, Ernemann U. Clinical predictors of transient ischemic attack, stroke, or death within 30 days of carotid angioplasty
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118. Boltuch J, Sabeti S, Amighi J, et al. Procedure-related complications and early neurological adverse events of unprotected and protected carotid stenting:
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119. Gray WA, Hopkins LN, Yadav S, et al. Protected carotid stenting in high-surgical-risk patients: the ARCHeR results. J Vasc Surg 2006;44:258 – 68.
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121. White CJ, Iyer SS, Hopkins LN, Katzen BT, Russell ME. Carotid stenting with distal protection in high surgical risk patients: the BEACH trial 30 day results.
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Systematic Review of the Perioperative Risks of Stroke or Death After Carotid
Angioplasty and Stenting
Emmanuel Touzé, Ludovic Trinquart, Gilles Chatellier and Jean-Louis Mas
Stroke. published online November 5, 2009;
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Comentarios, opiniones y revisiones
Revisión sistemática de los riesgos perioperatorios
de ictus y muerte tras la angioplastia carotídea
con implantación de stent
Emmanuel Touzé, PhD; Ludovic Trinquart, MSc; Gilles Chatellier, PhD; Jean-Louis Mas, MD
Antecedentes y objetivo. No se ha demostrado que la angioplastia carotídea con implantación de stent (ACIS) sea igual de
segura que la endarterectomía carotídea (EDAC) por lo que respecta a los riesgos de complicaciones periintervención,
aunque después del periodo postoperatorio, los riesgos observados son comparables, lo cual sugiere que la ACIS puede
ser una opción aceptable en pacientes seleccionados. Sin embargo, no se han establecido claramente los factores de
riesgo para el ictus y la muerte perioperatorios. El objetivo de este estudio fue estimar los riesgos absolutos de ictus o
muerte a 30 días tras la ACIS e investigar los orígenes de la heterogeneidad.
Métodos. Llevamos a cabo una búsqueda de artículos publicados entre enero de 1990 y junio de 2008, mediante el empleo
de las bases de datos de MEDLINE, EMBASE y COCHRANE, una búsqueda manual, libros de resúmenes de congresos
y sitios web oficiales. Dos revisores seleccionaron de manera independiente y por duplicado los artículos relativos a los
riesgos de la ACIS, con independencia del tipo de tratamiento, el diseño de estudio, el contexto o el idioma de publicación. Los 2 revisores se encargaron de realizar una extracción de los datos y de evaluar la calidad de los estudios.
Resultados. Se incluyeron un total de 206 estudios independientes (con 54.713 pacientes). El riesgo global de ictus o
muerte a 30 días fue del 4,7% (IC del 95%, 4,1 a 5,2), con una heterogeneidad sustancial entre los diversos estudios. Los
pacientes sintomáticos presentaban una probabilidad de sufrir complicaciones aproximadamente doble de la existente en
los pacientes con estenosis asintomáticas. El riesgo de ictus o muerte a 30 días fue del 7,6% (3,6 a 9,1) en los pacientes
sintomáticos y del 3,3% (2,6 a 4,1) en los pacientes asintomáticos. Los riesgos aumentaban con la edad, la hipertensión
y los antecedentes de enfermedad coronaria; no estaban relacionados con el sexo ni con la presencia de una oclusión
carotídea contralateral; y eran menores en los pacientes con una reestenosis carotídea tras la EDAC y en los tratados
utilizando un dispositivo de protección cerebral. Además, los riesgos han disminuido a lo largo del tiempo.
Conclusiones. Los riesgos de ACIS presentan una variación sustancial en los diversos estudios. En general son mayores
que los de la EDAC en pacientes sintomáticos. Es probable que algunos factores sean útiles para seleccionar a los candidatos adecuados para la ACIS. (Traducido del inglés: Systematic Review of the Perioperative Risks of Stroke or
Death After Carotid Angioplasty and Stenting. Stroke. 2009;40:e683-e693.)
Palabras clave: stroke n carotid disease n stenting n angioplasty n atherosclerosis n systematic review
L
a estenosis de la arteria carótida interna extracraneal explica del 15% al 20% de los ictus isquémicos, según cuál
sea la población estudiada1. La eficacia de la endarterectomía
carotídea (EDAC) para la prevención del ictus en pacientes
con estenosis carotídea está bien establecida, sobre todo en
los pacientes con estenosis sintomáticas1-3. La angioplastia carotídea con implantación de stent (ACIS), una posible
alternativa terapéutica a la EDAC, se ha evaluado en unos
pocos ensayos aleatorizados y en múltiples estudios no aleatorizados, con la participación de muchos especialistas, como
neurólogos, radiólogos, cardiólogos, cirujanos vasculares y
neurocirujanos, la mayor parte de los cuales han aplicado ya
esta técnica en su práctica clínica4. Sin embargo, en recientes
ensayos aleatorizados y metaanálisis no se ha podido demostrar que la ACIS sea igual de segura que la EDAC en lo relativo a los riesgos de complicaciones periintervención4–12 y las
guías terapéuticas actuales recomiendan que no se utilice la
ACIS en los pacientes que son candidatos adecuados para el
tratamiento quirúrgico2,3,13. No obstante, los ensayos clínicos
han indicado también que, después del periodo perioperatorio, el riesgo de ictus homolateral es muy bajo y comparable en los pacientes tratados con ACIS y con EDAC10,14,15,
Recibido el 8 de julio de 2009; revisión final recibida el 25 de agosto de 2009; aceptado el 4 de setiembre de 2009.
Université Paris Descartes, INSERM U894 (E.T., J.-L.M.), Hôpital Sainte-Anne, Service de Neurologie, e INSERM CIE4 (L.T., G.C.), Assistance
Publique-Hôpitaux de Paris, Unité de recherche clinique, Hôpital Européen Georges Pompidou, París, Francia.
Los dos primeros autores contribuyeron por igual a la obtención y análisis de los datos y a la redacción del artículo.
Correspondencia: Emmanuel Touzé, MD, PhD, Université Paris Descartes, INSERM U894, Department of Neurology, Hôpital Sainte-Anne, 1 rue
Cabanis, 75014 Paris, Francia. E-mail [email protected]
© 2009 American Heart Association, Inc.
Stroke está disponible en http://www.strokeaha.org
DOI: 10.1161/STROKEAHA.109.562041
22
Touzé y cols. Revisión sistemática de los riesgos perioperatorios de ictus y muerte... 23
Tabla 1. Estrategia de búsqueda en MEDLINE y EMBASE
Estrategia de búsqueda en PubMed
(“Carotid stenosis” Mesh AND (“stents” Mesh OR “angioplasty” Mesh
OR “angioplasty, balloon” Mesh ) AND (“treatment outcome” Mesh OR
“postoperative complications” Mesh OR “myocardial infarction” Mesh
OR “stroke” Mesh OR “brain ischemia” Mesh OR “death” Mesh OR
“death, sudden, cardiac” Mesh OR “mortality” Mesh )) OR (“carotid
stenosis” AND (“carotid angioplasty” OR “stent”*) AND (“stroke” OR
“myocardial infarction” OR “death” OR “mortality”) AND
(“1990” PDat :”2008/06” PDat ) AND (“humans” Mesh ) )
Estrategia de búsqueda en EMBASE
(“Carotid artery obstruction”/exp AND (“stent”/exp OR “angioplasty”/exp
OR “percutaneous transluminal angioplasty”/exp) AND (“treatment
outcome”/exp OR “postoperative complication”/exp OR “heart
infarction”/exp OR “cerebrovascular accident”/exp OR “stroke”/exp OR
“brain ischemia”/exp OR “death”/exp OR “sudden death”/exp) NOT
“review” /lim AND “humans” /lim AND 1990 –2008 /py)
lo cual sugiere que la ACIS puede ser una opción aceptable
en pacientes seleccionados que presentan un riesgo bajo de
complicaciones periintervención. Sin embargo, en la actualidad no existe ningún método que permita seleccionar a
los pacientes que son candidatos adecuados para una ACIS.
Además, aunque la ACIS se utiliza ampliamente en algunos
centros, no se sabe si el riesgo absoluto de la ACIS observado en los ensayos clínicos aleatorizados puede generalizarse
a la práctica clínica cotidiana.
Los riesgos de complicaciones tras la EDAC y su relación
con diferentes subgrupos se han estimado en varios estudios y
metaanálisis16–20, pero no existen datos similares par la ACIS.
Algunos estudios han puesto de manifiesto que es probable
que el riesgo de complicaciones tras la ACIS esté relacionado
con algunas características de los pacientes y con aspectos
técnicos. Sin embargo, el número de complicaciones observadas en estudios específicos fue generalmente bajo, y ello
impide extraer una conclusión fiable. Por otra parte, muchos
de los estudios se han centrado en pacientes con un riesgo
quirúrgico percibido alto, lo que lleva a plantear la hipótesis
de que estos pacientes deben ser candidatos adecuados para
una ACIS4,21. Sin embargo, es posible que las comorbilidades
asociadas a un riesgo perioperatorio superior con la EDAC
aumenten también el riesgo periintervención en la ACIS.
Así pues, hemos realizado una revisión sistemática de los
estudios en los que se ha descrito el riesgo de ictus, muerte e
infarto de miocardio (IM) tras la ACIS, con objeto de estimar
los riesgos absolutos e investigar la posible relación entre los
riesgos observados y el diseño del estudio, la población incluida, los factores clínicos y los aspectos técnicos.
Métodos
Antes de realizar la revisión, elaboramos un protocolo que
incluía los fundamentos y objetivos, junto con una descripción de los métodos de investigación propuestos y los planes
para la obtención y el análisis de los datos. El manuscrito se
preparó según lo establecido en las guías MOOSE22.
Criterios de selección y estrategia de búsqueda
Se consideraron elegibles para la revisión los estudios que
cumplían las siguientes características: (1) incluían a pacien-
tes con estenosis sintomáticas y/o asintomáticas situadas en
la región de la bifurcación carotídea; (2) los pacientes eran
tratados con angioplastia, fuera cual fuera el tipo de tratamiento concreto utilizado (angioplastia con balón con o sin
implantación de stent), la vía de acceso arterial y el uso de
protección cerebral; y (3) era posible extraer información relativa al número de episodios (ictus, IM o muerte). Se excluyeron los estudios para los que se había reclutado tan solo a un grupo de población específico (reestenosis tras una
EDAC, estenosis post-radioterapia, displasia fibromuscular,
disección carotídea, y pacientes tratados en un contexto de
urgencia).
Realizamos una búsqueda de los artículos publicados entre enero de 1990 y junio de 2008 sobre los riesgos de ictus,
muerte o IM tras una ACIS, con independencia del diseño de
estudio, el contexto o el idioma de publicación. Se llevaron
a cabo búsquedas electrónicas con el empleo de MEDLINE
y EMBASE , utilizando tanto los términos de clasificación
de temas médicos (medical subject heading terms) como las
palabras del texto (Tabla 1), y en la base de datos de la COCHRANE Library (CENTRAL y DARE). Realizamos búsquedas manuales en las listas de bibliografía de todos los artículos incluidos, de todos los artículos de revisión relevantes,
de nuestros archivos personales y de las páginas de índice
de las 3 revistas en las que se había identificado un mayor
número de artículos elegibles en las búsquedas electrónicas
(Journal of Vascular Surgery, Journal of Endovascular Therapy y Catheter Cardiovascular Interventions). Con objeto
de identificar los estudios recientes todavía no publicados en
forma de artículos completos, realizamos también una búsqueda en los libros de resúmenes de los congresos recientes (Joint World Congress on Stroke 2006, American Heart
Association International Stroke Conferences 2007 y 2008,
European Stroke Conferences 2007 y 2008, congresos de la
Cardiovascular and Interventional Radiological Society of
Europe 2006 y 2007, congresos de Transcatheter Cardiovascular Therapeutics 2006 y 2007, sesiones del American College of Cardiology Scientific 2007 y 2008, y congresos de la
Society of Interventional Radiology 2007 y 2008), así como
de los sitios web del registro de ensayos clínicos (www.clinicaltrials.gov), la Food and Drug Administration de EEUU
(www.fda.gov) y la Agencia Europea del Medicamento
(www. emea.europa.eu).
Selección de los estudios y obtención de los datos
Dos revisores se encargaron de evaluar, de manera independiente y por duplicado, la elegibilidad de las referencias bibliográficas identificadas mediante la estrategia de búsqueda,
mediante el examen de los títulos y luego de los resúmenes
de los artículos. En cada paso, las discrepancias aparecidas se
resolvieron mediante el debate. La selección final se realizó
tras haber revisado los artículos completos correspondientes
a todos los artículos que o bien cumplían los criterios de selección o bien no estaba del todo clara la selección según lo
indicado en el resumen. En los casos de publicaciones múltiples relativas a la misma población, se eligió la que presentaba un número más elevado de pacientes para el análisis del
riesgo absoluto. Se obtuvieron datos adicionales de subgrupos del ensayo SPACE solicitándolos a los autores8. Los 2
24 Stroke Marzo 2010
Medline y Embase
53 referencias de otras fuentes
Cochrane Library, FDA, EMEA, libros de resúmenes,
archivos personales, listas de bibliografía
1.796 títulos examinados
605 resúmenes examinados
457 referencias elegibles para
una revisión completa
Figura 1. Diagrama de flujo de la selección de los estudios.
510 referencias analizadas
con el texto completo
Población no independiente (149)
Resultados no disponibles (69)
Muy seleccionados (56)
206 poblaciones independientes
234 referencias incluidas
revisores se encargaron de extraer los datos mediante un formulario estandarizado (que puede solicitarse a los autores).
La calidad de cada estudio fue evaluada con un esquema ya
existente23 que adaptamos a nuestro contexto y que incluía
la siguiente lista de criterios: (1) diseño (ensayo aleatorizado
frente a estudios de cohortes/registros), (2) contexto (estudio
de un solo centro frente a estudio multicéntrico), (3) forma de
inclusión de los pacientes (prospectiva frente a retrospectiva,
y consecutiva frente a no consecutiva), (4) descripción de la
población (adecuada frente a insuficiente) y (5) evaluación
del resultado (evaluación sistemática por un neurólogo tras la
intervención, sí frente a no). La descripción de la población
se consideró adecuada cuando se describían suficientemente el marco de referencia del muestreo, el reclutamiento, los
criterios de inclusión y exclusión y las características basales
de la muestra en estudio. La evaluación sistemática por parte
de un neurólogo hacía referencia a que todos los pacientes
fueran examinados por un neurólogo a los 30 días (resultados
a los 30 días) o antes del alta (episodios periintervención o
intrahospitalarios), tanto si el paciente presentaba un episodio de la variable de valoración como si no.
Síntesis y análisis de los datos
Las variables de valoración principales fueron los riesgos a
30 días de ictus; ictus o muerte; o ictus, IM o muerte. Las
variables de valoración secundarias fueron los riesgos intrahospitalarios y periintervención (en las primeras 24 horas).
Cuando no estaba claro el momento exacto de la evaluación
de las complicaciones, sin un seguimiento sistemático a los
30 días, consideramos que se trataba de episodios de complicaciones periintervención. Las estimaciones combinadas
del riesgo se calcularon por separado para las diferentes variables de valoración. Cada proporción individual obtenida
se transformó primero en una cantidad con la transformación
estabilizadora de varianzas de Freeman-Tukey24. Se calculó una media ponderada de las proporciones transformadas,
utilizando un modelo de efectos aleatorios de DerSimonianLaird25. La proporción combinada se calculó mediante la retrotransformación de esta media ponderada26.
Con objeto de explorar los posibles orígenes de la heterogeneidad, realizamos en primer lugar comparaciones de
subgrupos según los siguientes factores: forma de presentación clínica (sintomática frente a asintomática; ictus frente a
ataque isquémico transitorio; episodio cerebral frente a episodio ocular), edad (>75 a 80 frente a <75 a 80 años), sexo,
diabetes mellitus, enfermedad coronaria (EC), enfermedad
arterial periférica (EAC), oclusión carotídea contralateral,
reestenosis tras la EDAC frente a lesión aparecida de novo, estructura de la placa (ulcerada frente a lisa, presencia
de calcificación), momento de realización de la ACIS (<14
días frente a >14 días tras el episodio de isquemia cerebral),
lado de la lesión tratada y uso de un dispositivo de protección cerebral. Estas comparaciones se llevaron a cabo dentro de cada estudio. Calculamos los riesgos relativos (RR)
combinados para el conjunto de todos los estudios utilizando
un metaanálisis de efectos fijos, según el método de MantelHaenszel, o bien con el empleo de un metaanálisis de efectos aleatorios de DerSimonian-Laird, según fuera apropiado.
A continuación realizamos comparaciones indirectas de los
riesgos absolutos combinados, según la forma de presentación clínica y las características de calidad del estudio que
se han definido antes y evaluamos los posibles cambios del
riesgo a lo largo del tiempo, mediante un análisis de metarregresión. Utilizamos un modelo normal logístico que especificaba la distribución binomial de la variable dependiente
(riesgo de ictus o muerte a 30 días) y un efecto aleatorio para
tener en cuenta la varianza compartida dentro del estudio27.
Se calculó el año de mitad de cohorte, definido como el punto medio del periodo de inclusión, para cada estudio si se disponía de información sobre el periodo de inclusión, y se consideró una covariable. Evaluamos los sesgos de publicación
mediante un análisis visual simple de los gráficos de embudo
en el metaanálisis de los riesgos absolutos, puesto que no hay
pruebas estadísticas validadas para la detección de la asimetría, y utilizamos gráficos de embudo y la prueba de Egger
en las comparaciones de subgrupos28. En todos los análisis,
se evaluó la inconsistencia de los resultados en los diversos
estudios utilizando el parámetro estadístico Q de Cochran y
Tabla 2. Calidad, características de la población y aspectos técnicos
de los estudios incluidos
Número
Número de
de estudios (%), pacientes (Número
de intervenciones)
Total 206*
Calidad del estudio
Tabla 3. Estimaciones combinadas de los riesgos absolutos de
ictus, muerte o IM, según el momento de valoración de los
resultados tras la ACIS
Ictus
Ictus, muerte
Ictus, IM,
muerte
Episodios
a 30 días
Contexto
Multicéntrico
36 (17)
34 898 (35 502)
113
63
170 (83)
19 815 (20 684)
Número de
estudios
incluidos
118
Un solo centro
10 (5)
1613 (1613)
Número de
pacientes
27 186
25 237
17 291
Número de
intervenciones
28 149
26 145
17 858
Diseño
ECA (EDAC frente a ACIS)
ECA (otros)†
3 ( 1)
144 (144)
193 (94)
52 956 (54 430)
Prospectiva
83 (40)
24 878 (25260)
Retrospectiva
42 (20)
8580 (8881)
No se indica claramente
81 (40)
21 255 (22045)
Riesgo
combinado
(IC del 95%)
P(het)
119 (58)
29 485 (30250)
I² (IC del 95%)
87 (42)
25 228 (25936)
Episodios
intrahospitalarios
Se describe el marco de referencia
del muestreo
Se describen los criterios de inclusión
154 (75)
140 (68)
38 056 (39 354)
36 487 (37 429)
Se describen las características basales
132 (64)
Evaluación realizada por un neurólogo
Registro
Inclusión de pacientes
Consecutiva
No se indica claramente
Descripción de la población
3,9% (3,4 a 4,4)
0,0001
67% (60 a 73)
4,7% (4,1 a 5,2)
0,0001
69% (62 a 74)
5,3% (4,6 a 6,0)
0,0001
64% (52 a 72)
Número de
estudios
incluidos
53
48
19
34832 (3552)
Número de
pacientes
11 694
7912
1723
79 (39)
26 286 (26 835)
12 073
8243
1806
Se indica la definición de la variable
de valoración de ictus
87 (43)
37 499 (38 292)
Número de
intervenciones
Presencia de al menos 1 neurólogo
en la relación de autores
66 (32)
9075 (9410)
Evaluación de las variables de valoración
Número de
estudios con
datos disponibles
Mediana (RIC)
Características de la población
Número de pacientes
206
90 (41 to 204)
Número de intervenciones
20 6
94 (43 to 215)
Porcentaje de varones
179
71 (65 to 80)
Media de edad, años
180
70 (67 to 71)
Porcentaje de pacientes sintomáticos
180
50 (33 to 78)
Porcentaje de pacientes diabéticos
128
31 (24 to 38)
Porcentaje de pacientes con
reestenosis carotídea
95
14 (7 to 24)
estenosis carotídea post-irradiación
47
5 (2 to 9)
Porcentaje de pacientes con EC
104
60 (40 to 71)
Porcentaje de pacientes con EAC
44
28 (20 to 37)
oclusión carotídea contralateral
79
10 (6 to 14)
Riesgo
combinado
(IC del 95%)
P(het)
3,9% (3,2 a 4,6)
0,0001
0,0001
0,11
I² (IC del 95%)
56% (41 a 68)
54% (36 a 67)
30% (0 a 60)
Ningún paciente tratado con
protección cerebral, n estudios (%)
201
54 (27)
Todos los pacientes tratados con
protección cerebral, n estudios (%)
201
71 (35)
Porcentaje de intervenciones
satisfactorias, mediana (RIC)
109
98 (97–100)
RIC indica rango intercuartiles.
*Incluye también resúmenes.
†ECA en los que se comparan diferentes estrategias en pacientes tratados
con ACIS.
4,6% (3,5 a 5,9)
53
40
13
Número
de pacientes
9003
3893
979
Número de
intervenciones
9413
4199
1006
3,7% (2,6 a 5,0)
4,0% (2,6 a 5,7)
Episodios
periintervención*
Número
de estudios
incluidos
Riesgo
combinado
(IC del 95%)
P(het)
Aspectos técnicos
4,1% (3,3 a 5,0)
I² (IC del 95%)
3,5% (2,7 a 4,4)
0,0001
71% (61 a 78)
0,0001
66% (53 a 76)
0,23
21% (0 a 59)
P (het) indica el valor de P asociado a la prueba de χ² para la heterogeneidad;
I², porcentaje de la variabilidad en las estimaciones del efecto que se debe a la
heterogeneidad y no al error de muestreo (aleatorio). Se calcularon estimaciones
combinadas del riesgo por separado para las distintas variables de valoración.
Cada proporción individual se transformó primero en una cantidad con la transformación estabilizadora de la varianza de Freeman-Tukey24. Se calculó una
media ponderada de las proporciones transformadas mediante un modelo de
efectos aleatorios de DerSimonian-Laird24. Se calculó la proporción combinada
mediante la retrotransformación de esta media ponderada.
*Incluye también los episodios en los que no estaba claro el momento de
la determinación.
el parámetro estadístico I2 con el IC del 95% asociado; este
último correspondía al porcentaje de variabilidad debida a la
heterogeneidad entre los estudios y no al error de muestreo
Figura 2. Valores combinados de los RR de ictus y de ictus o muerte en diferentes subgrupos. p(het) indica el valor de probabilidad
asociado a la prueba estadística de χ2 de Cochran para la heterogeneidad; I2, porcentaje de la variabilidad en las estimaciones del efecto
que se debe a la heterogeneidad y no al error de muestreo (aleatorio); NA, no evaluable; AIT, ataque isquémico transitorio; y p(sig), valor
de p para la significación. Utilizamos un modelo de efectos fijos para calcular las estimaciones combinadas, excepto cuando sucedía que
p(het) < 0,10 o I2 > 30%, en cuyo caso se utilizó un modelo de efectos aleatorios. Véanse las Figuras II y III del suplemento para los valores
de cada metaanálisis individual. Se combinaron los resultados evaluados a los 30 días, en el momento del alta, durante la intervención o
cuando no se conocía el momento de valoración. La comparación corresponde a sí frente a no, salvo que se indique lo contrario. A, RR
combinado (IC del 95%) para ictus o muerte (véase también la Figura II del suplemento). B, RR combinado (IC del 95%) para ictus (véase
también la Figura III disponible solamente online).
(aleatorio)29,30. Según el manual Cochrane, la heterogeneidad
se clasificó como moderada (I2 ≥30%), substancial (I2 ≥50%)
o considerable (I2 ≥75%)31. Consideramos significativo un
valor de probabilidad bilateral <0,05. El análisis estadístico
se realizó con los programas SAS versión 9.1 y MIX (http://
mix-for-metaanálisis.info).
Resultados
De los 1.796 artículos identificados en nuestra búsqueda
electrónica en MEDLINE y EMBASE, se examinaron 605
resúmenes y se obtuvieron 457 artículos para la evaluación
del texto completo (Figura 1). Identificamos otros 53 artículos o resúmenes a partir de otras fuentes. De las 510 re-
Figura 3. Riesgo absoluto de ictus
o muerte a 30 días (%) tras la ACIS
en 91 estudios (18.538 pacientes)
según el año de mitad de cohorte,
junto con una metarregresión de
efectos aleatorios de resumen.
El área de cada círculo es
inversamente proporcional a la
varianza del riesgo absoluto.
ferencias bibliográficas analizadas de manera detallada, 206
correspondían a estudios independientes que fueron considerados elegibles (133 solamente en cuanto al riesgo absoluto, 62 en cuanto al riesgo absoluto y los subgrupos, y 11
en cuanto a los subgrupos solamente). Dada la existencia de
múltiples publicaciones de algunos registros, con diferentes
análisis de subgrupos, los 206 estudios independientes dieron origen a 234 presentaciones de datos (212 artículos completos, 19 resúmenes, 2 documentos de la Food and Drug
Administration de EEUU y 1 documento presentado en un
sitio web) relevantes para nuestro análisis. En la Tabla 2 se
presentan las características resumidas de los estudios incluidos, y la lista de referencias bibliográficas y características
de los trabajos individuales pueden consultarse en la Tabla I
del suplemento disponible online en http://ictus.ahajournals.
org. En el conjunto de 206 estudios independientes (54.713
pacientes), había 10 ensayos clínicos aleatorizados (ECA)
en los que se comparaba la ACIS con la EDAC (1.613 pa
cientes)5,7,8,21,32–37, 3 ECA en los que se comparaban estrategias diferentes en pacientes tratados con ACIS (144 pacientes)38–40 y 193 registros (52.956 pacientes). Había 32 estudios
(2.922 pacientes) en los que un 95% o más de los pacientes
tenían una estenosis sintomática, 2 estudios (136 pacientes)
en los que el 95% o más de los pacientes tenían una estenosis
carotídea asintomática, y 172 estudios (51.655 pacientes) que
incluían a pacientes tanto sintomáticos como asintomáticos.
Aproximadamente la mitad (51%) de los estudios iniciaron el
reclutamiento de pacientes antes de 2000.
Como se muestra en la Tabla 2, un 83% de los estudios
se habían realizado en un solo centro y en el 40% se indicaba que eran prospectivos. La descripción de la población era
adecuada en el 46%, y la evaluación de los resultados fue
realizada por un neurólogo independiente en el 40% de los
estudios publicados en forma de artículos completos. Se identificó una población plenamente descrita y una evaluación
neurológica de los resultados en 49 (26%) de los estudios publicados en forma de artículo completo. De los 172 estudios
que incluyeron a pacientes sintomáticos y asintomáticos, 36
(21%) presentaron los riesgos de ACIS estratificados según
la forma de presentación clínica. De los 173 estudios que
indicaban claramente el tipo de tratamiento realizado, 161
(93%) eran estudios en los que más del 90% de los pacientes
fueron tratados con implantación de stents.
Las características principales de los ECA y los registros
fueron muy similares en lo relativo a la edad (mediana, 69
frente a 70 años), la proporción de varones (mediana, 71%
frente a 71%), la proporción de pacientes con oclusión carotídea contralateral (mediana, 10% frente a 10%) y la proporción
de pacientes con EC (mediana, 57% frente a 61%). La proporción de pacientes sintomáticos fue mayor en los ECA que en
los registros (mediana, 81% frente a 49%). En cambio, en los
registros era más probable que en los ECA haber incluido a pacientes con reestenosis tras una EDAC (mediana, 15% frente
a 8%), la presencia de pacientes con diabetes (mediana, 32%
frente a 24%) y el haber tratado a pacientes utilizando dispositivos de protección cerebral (mediana, 83% frente a 42%).
Figura 4. Riesgo combinado de ictus o muerte a 30 días tras la ACIS, estratificado según la indicación clínica y con una estratificación
adicional respecto al diseño de estudio y a si los resultados fueron evaluados o no por un neurólogo. La línea a trazos corresponde al
riesgo a 30 días combinado para los diversos ECA y en todos los datos de registros. Se realizó una evaluación neurológica independiente
en todos los ECA. Algunos ECA no pudieron ser incluidos en este análisis porque no se dispuso de una evaluación de los resultados de
ictus o muerte a los 30 días.
En la Tabla 3 se indican las estimaciones combinadas de
los riesgos absolutos según el momento en el que se realizaba
la evaluación del resultado. El riesgo a 30 días de ictus fue del
3,9% (IC del 95%, 3,4 a 4,4; 118 estudios; 27.186 pacientes);
el de ictus o muerte fue del 4,7% (IC del 95%, 4,1 a 5,2; 113
estudios; 25.237 pacientes); y el de ictus, muerte o IM fue del
5,3% (IC del 95%, 4,6 a 6,0; 63 estudios; 17.291 pacientes).
Los correspondientes riesgos intrahospitalarios y periintervención fueron ligeramente inferiores. Sin embargo, había
una heterogeneidad sustancial entre los distintos estudios. La
exclusión de los resúmenes o de los estudios postcomercialización que podrían haber incluido a pacientes considerados
también en los estudios individuales publicados, no modificó
las estimaciones (datos no mostrados).
Por lo que respecta a la calidad de los estudios, los análisis de
metarregresión indicaron que el riesgo de ictus o muerte a 30
días no estaba relacionado con el contexto de realización del estudio (multicéntrico 4,8% frente a unicéntrico, 4,6%, p = 0,77),
ni con el reclutamiento de pacientes consecutivos (sí 4,6% frente
a no 4,8%, p = 0,89). Sin embargo, el riesgo era más alto cuando
había una descripción adecuada de la población (sí 5,2% frente
a no 4,0%, p =0,04), en el caso de una inclusión prospectiva (sí
5,2% frente a no 4,2%, p = 0,07), y cuando la evaluación era
realizada por un neurólogo (sí 5,4% frente a no 4,1%, p = 0,02).
No observamos indicio alguno de sesgo de publicación en el
análisis visual de los gráficos de embudo del tamaño muestral de
los estudios en relación con el riesgo absoluto de ictus o muerte,
puesto que había igual número de estudios de menor tamaño con
riesgos de complicaciones altos y bajos (Figura I del suplemento, accesible online en http://ictus.ahajournals.org). Los resultados fueron similares para el ictus y para el conjunto de ictus, IM
o muerte (datos no mostrados).
En la Figura 2 se presenta un resumen de los RR combinados de ictus y de ictus o muerte con la ACIS para los diferentes análisis de subgrupos preespecificados, por separado
en función de los síntomas clínicos, las características de los
pacientes (incluidos los factores de riesgo vascular y los antecedentes patológicos previos), las características de la estenosis y los factores técnicos. (Pueden consultarse los gráficos
de Forest de los correspondientes análisis en las Figuras II y
III del suplemento). Las estenosis sintomáticas (RR = 1,86;
IC del 95%, 1,61 a 2,14), los episodios cerebrales frente a los
oculares (RR = 2,28; IC del 95%, 1,08 a 4,77), la edad >75
a 80 años (RR = 1,93; IC del 95%, 1,66 a 2,24), la EC (RR
= 1,41; IC del 95%, 0,97 a 2,06), los antecedentes de bypass
arterial coronario (RR = 2,21; IC del 95%, 1,03 a 4,72), y
la EAC (RR = 2,04; IC del 95%, 0,92 a 4,52) se asociaron
a un riesgo superior de ictus o muerte tras la ACIS. Hubo
también una tendencia a un riesgo superior de complicaciones en los pacientes que presentaban placas calcificadas. En
cambio, el riesgo de ictus o muerte tras la ACIS fue inferior
en los pacientes tratados por una enfermedad carotídea causada por una reestenosis tras una EDAC, en comparación con
los tratados por una estenosis carotídea aterosclerótica (RR
= 0,45; IC del 95%, 0,28 a 0,71). El empleo de sistemas de
protección cerebral se asoció a un menor riesgo de ictus o
muerte (RR = 0,57; IC del 95%, 0,43 a 0,76). El riesgo de
ictus o muerte no estaba relacionado con el sexo, la oclusión
carotídea contralateral, la diabetes mellitus, la ulceración de
la placa, el momento de realización de la ACIS o el lado de la
lesión tratada. Se observaron resultados similares en cuanto
al resultado de ictus, excepto porque la hipertensión se asociaba de manera significativa a un riesgo superior de complicaciones (RR = 1,86; IC del 95%, 1,30 a 2,68). A diferencia
de la heterogeneidad sustancial observada en las estimaciones combinadas de los riesgos absolutos, la heterogeneidad
en estas estimaciones combinadas de los RR fue nula o tan
solo moderada. No observamos indicio alguno de sesgos de
publicación en estos análisis en los gráficos de embudo ni en
la prueba de Egger (datos no mostrados).
El riesgo combinado de ictus a 30 días fue del 6,3% (IC del
95%, 4,8 a 8,0) en los estudios con un año de mitad de cohorte anterior a 1998, del 5,0% (IC del 95%, 4,1 a 5,9) en los
estudios con un año de mitad de cohorte situado entre 1998
y 2002, y del 3,9% (IC del 95%, 3,0 a 4,9) en los estudios
con un año de mitad de cohorte posterior a 2002. Un análisis
de metarregresión tomando el año de mitad de cohorte como
covariable puso de manifiesto una reducción significativa del
riesgo de ictus o muerte a los 30 días a lo largo del tiempo,
que correspondía a una reducción del RR de ≈6% anual (91
estudios, p <0,0001; Figura 3). Se obtuvo un resultado similar al utilizar el año de publicación en vez del año de mitad
de cohorte (p <0,0001) o al considerar el ictus solamente en
vez del ictus o la muerte (datos no presentados).
En la Figura 4 se muestran los riesgos absolutos combinados a 30 días para el ictus o la muerte, estratificados según la
indicación clínica y con una estratificación adicional según
el diseño del estudio y según que los resultados fueran evaluados o no por un neurólogo. En los pacientes con estenosis
sintomáticas, el riesgo absoluto global de ictus o muerte a
los 30 días fue del 7,6% (IC del 95%, 6,3 a 9,1; 42 estudios;
4.910 pacientes). Ese riesgo era superior en la ECA (10,8%;
IC del 95%, 6,8 a 15,5) en comparación con los registros que
incluían solamente a pacientes sintomáticos (7,3%; IC del
95%, 5,3 a 9,6; p = 0,16) y en comparación con los subgru-
pos de pacientes sintomáticos incluidos en otros registros
(7,0%; IC del 95%, 5,2 a 9,0; p = 0,04). El riesgo absoluto
de ictus o muerte a 30 días no fue significativamente mayor
en los estudios en los que hubo una evaluación neurológica
independiente en comparación con los estudios en los que
no estaba claro que el método de evaluación de los resultados estuviera a cargo de un neurólogo independiente. En los
pacientes con estenosis asintomáticas, sólo hubo un ECA en
el que no se hubiera evaluado claramente el riesgo de ictus
o muerte a 30 días34, y 1 de los estudios de registro incluyó
únicamente a pacientes asintomáticos41. El riesgo absoluto
global de ictus o muerte fue del 3,3% (IC del 95%, 2,6 a 4,1;
23 estudios; 8.504 pacientes). Al igual que para la estenosis
sintomática, los riesgos no fueron significativamente mayores en los estudios en los que se utilizó una evaluación neurológica independiente. Todos estos resultados fueron similares
al utilizar la presencia de al menos 1 neurólogo en la relación
de autores como indicador de calidad, en vez de la evaluación neurológica independiente (datos no presentados).
Discusión
En primer lugar, hemos evidenciado que el riesgo global de
ictus o muerte a 30 días después de una ACIS es de ≈5%, pero presenta variaciones sustanciales en los distintos estudios.
Estas variaciones pueden ser consecuencia de diferencias en
la combinación de tipos de casos, el diseño, la calidad del estudio o la pericia de los médicos que realizan las intervenciones. En segundo lugar, los riesgos de la ACIS dependen de
la indicación clínica, de tal manera que los pacientes sintomáticos tienen una probabilidad de presentar complicaciones
aproximadamente doble de la de los pacientes con estenosis asintomáticas; y dependen también de características de
los pacientes que son asimismo factores de riesgo quirúrgico
elevado, como la edad, la hipertensión y los antecedentes de
EC (incluido el bypass arterial coronario). En cambio, otros
factores de riesgo quirúrgico elevado establecidos o bien no
parecieron influir en el riesgo de complicaciones de la ACIS
(sexo femenino y oclusión carotídea contralateral) o bien se
asociaron incluso a un riesgo inferior (reestenosis carotídea
tras una EDAC). En consecuencia, nuestros resultados sugieren claramente que hay factores clínicos simples que es probable que faciliten la selección de los candidatos adecuados
para la ACIS en futuros ensayos clínicos de comparación de
esta técnica con la EDAC, y finalmente en la práctica clínica.
Por último, nuestros resultados sugieren que los riesgos del
tratamiento han disminuido a lo largo del tiempo, y que el
uso de un dispositivo de protección cerebral se asocia a un
riesgo de complicaciones inferior.
Identificamos un total de 206 estudios que presentaban datos sobre los riesgos de la ACIS, en 54.713 pacientes. Debe
señalarse que los pacientes de ECA suponían solamente un
3% de la población total, lo cual subraya el grado en el que
esta técnica se ha venido aplicando en la práctica clínica a
pesar del bajo nivel de la evidencia existente. Dada la heterogeneidad sustancial existente entre los estudios, nuestras estimaciones combinadas de los riesgos operatorios absolutos
no pueden interpretarse de manera directa. Sin embargo, el
IC del 95% obtenido en un metaanálisis de efectos aleatorios describe bien la incertidumbre relativa al riesgo medio.
Por ejemplo, para el conjunto de todos los estudios, el riesgo
de ictus o muerte a 30 días fue, con el intervalo de confianza del 95%, al menos igual al 4,1% y de hasta un 5,2%. Es
interesante señalar que se ha observado una heterogeneidad
similar en revisiones sistemáticas previas de los riesgos de la
EDAC16–18.
La heterogeneidad existente entre los estudios tienen varios orígenes que pudimos identificar. Está claramente establecido que el efecto beneficioso de la EDAC depende
en gran medida de la indicación clínica, de tal manera que
se observa un efecto beneficioso superior en los pacientes
sintomáticos en comparación con los asintomáticos, así como que el riesgo de complicaciones perioperatorias es superior en los pacientes sintomáticos17,18,42,43. En una revisión sistemática anterior se observó que solamente ≈25%
de los estudios realizados en la EDAC habían estratificado
sus resultados en función de que los pacientes fueran asintomáticos o sintomáticos16. De forma análoga, nosotros observamos que solamente un 21% de los estudios de la ACIS
presentaban los riesgos estratificados según la indicación
clínica. Hemos evidenciado que, al igual que en la EDAC,
los pacientes sintomáticos tienen una probabilidad aproximadamente doble de la de los pacientes asintomáticos de
sufrir complicaciones después de la ACIS. Este resultado se
basa en análisis de subgrupos, es decir, en la comparación
de los pacientes sintomáticos y asintomáticos dentro de los
mismos estudios, y no observamos una heterogeneidad entre los distintos estudios a este respecto. Para los pacientes
sintomáticos, observamos que el riesgo de ictus o muerte a
30 días de la ACIS era del 7,6%, con un límite inferior del
IC del 95% del 6,3%, valor éste que es superior al riesgo
a 30 días asociado a la EDAC según lo observado en una
revisión sistemática anterior (5,1%; IC del 95% 4,6 a 5,6)16.
Este nivel de riesgo es también superior al umbral de riesgo
establecido por los comités ad hoc de las guías del American Heart Association Stroke Council, que indican que el
riesgo combinando de ictus y muerte como consecuencia
de la EDAC no debe ser superior al 5% para los pacientes
con ataques isquémicos transitorios y al 7% en los pacientes con ictus2,3. Aun siendo cuestionable, esta comparación
de los riesgos absolutos combinados concuerda plenamente
con el metaanálisis de ECA de comparación de la ACIS con
la EDAC en pacientes sintomáticos y pone de manifiesto
que la ACIS se asocia a un aumento del 40% en el riesgo
de ictus o muerte a 30 días12. Hemos observado también
que el riesgo fue mayor en los ECA en comparación con
los registros. Es probable que la definición de la estenosis
sintomática fuera diferente en los distintos estudios, aunque
esta información no puede extraerse con facilidad de las
publicaciones (por ejemplo, algunos registros consideraban
los ictus correspondientes a cualquier territorio o en cualquier periodo de tiempo). Además, al igual que en el caso
de la EDAC18, nuestros resultados sugieren que la calidad
de la evaluación neurológica explica en parte las diferencias
observadas. Aunque la mayoría de los pacientes incluidos
en los registros presentaban estenosis asintomáticas, obtuvimos datos específicos muy limitados sobre los riesgos de la
ACIS en esos pacientes. El riesgo global de ictus o muerte
a 30 días con la ACIS fue del 3,3%, con un límite inferior
del IC del 95% de 2,6%. Ese nivel de riesgo está próximo al
que se da con la EDAC (2,8%; IC del 95%, 2,4 a 3,2)16 y al
umbral de riesgo del 3% establecido en las directrices para
la estenosis asintomática2,3.
Muchos registros se han centrado en los pacientes que
tienen un riesgo quirúrgico elevado según un conjunto de
criterios, que varían en número y tipo, y han planteado la
hipótesis de que esos pacientes debieran ser candidatos adecuados para la ACIS4. Los factores que se citan con frecuencia como asociados a un riesgo quirúrgico superior son
factores anatómicos como las lesiones no accesibles quirúrgicamente, la EDAC o la irradiación cervical previas,
la edad avanzada, la oclusión carotídea contralateral y las
comorbilidades médicas. Sin embargo, no hay una evidencia que indique que en los pacientes de riesgo quirúrgico
elevado se obtenga un efecto beneficioso con alguna otra
estrategia de revascularización en comparación con el tratamiento médico solo44. Además, es posible que las comorbilidades asociadas a un mayor riesgo perioperatorio en la
EDAC aumenten también el riesgo periintervención de la
ACIS. Los estudios en los que se ha investigado si los factores que identifican a los pacientes de riesgo quirúrgico
elevado tienen alguna influencia en los riesgos de la ACIS
han tenido generalmente una potencia estadística baja para
poder extraer conclusiones fiables. Aunque los análisis previos de ECA y de registros han indicado de manera uniforme que la edad tiene tan solo una influencia pequeña en el
riesgo de complicaciones tras la EDAC45, los pacientes ancianos se consideran un grupo de riesgo quirúrgico elevado
y posibles candidatos adecuados para la ACIS. De hecho,
nosotros observamos que la edad se asociaba a un aumento
de ≈2 veces en el riesgo de complicaciones tras la ACIS, lo
cual sugiere que la edad tienen más influencia en los riesgos
de la ACIS que en los riesgos de la EDAC. Es interesante
señalar que varios estudios han indicado que los pacientes
de mayor edad tienen una mayor probabilidad de presentar
vasos tortuosos con una calcificación intensa que probablemente aumentan el riesgo de embolización durante la manipulación de la guía y los cambios de catéter en algunas
de las fases de la ACIS46,47. Otra observación importante
de nuestro análisis es que, a diferencia de la EDAC, en la
que las mujeres tienen un riesgo de complicaciones superior
al de los varones, los riesgos de la ACIS no muestran una
relación con el sexo. Sin embargo, aunque en ambos casos
están próximos a 1 y no son significativos, los RR combinados de las mujeres respecto a los varones en cuanto al
ictus y en cuanto al ictus o la muerte, se encuentran a cada
lado del valor 1. De hecho, los resultados obtenidos para
el ictus eran consecuencia en gran parte de los del registro
CAPTURE, en el que las mujeres presentaron un riesgo de
ictus ligeramente superior en el análisis univariado, pero no
en los análisis multivariados 48. La ausencia de efecto del
sexo sobre el riesgo de ACIS se ha demostrado también en
2 estudios recientes, publicados fuera del periodo de inclusión definido para nuestra revisión sistemática49,50. La
inclusión de esos estudios no hubiera modificado nuestras
estimaciones [RR combinado para el ictus = 1,02; IC del
95%, 0,87 a 1,27; p(het) = 0,87; RR combinado para el ictus
o la muerte = 0,90; IC del 95%, 0,74 a 1,10; p(het) =0,84].
Nuestra observación de que los riesgos de la ACIS no dependen de la oclusión carotídea contralateral y de que son
inferiores en los pacientes con una reestenosis tras la EDAC
es también importante, puesto que permite identificar a una
posible población diana en la que la ACIS podría compararse con la EDAC. Por último, aunque se obtuvieron a partir
de datos más limitados, y coincidiendo con lo indicado por
datos previos sobre la EDAC, nuestros resultados sugieren
que los riesgos de la ACIS son mayores en los pacientes
que sufrieron un episodio cerebral en comparación con los
que presentaron un episodio ocular, y que los antecedentes
previos de EC pueden no ser útiles para la selección de los
candidatos adecuados para la ACIS.
Hay algunas razones que podrían explicar que los factores
de riesgo para las complicaciones puedan diferir en la EDAC
y la ACIS. El mayor riesgo de complicaciones tras la EDAC
en las mujeres suele atribuirse al hecho de que la arteria carótida interna es más pequeña en ellas que en los varones, lo
cual predispone a los errores técnicos o a la trombosis postoperatoria inmediata, si bien esta hipótesis ha sido puesta en
duda51,52. La cirugía de la reestenosis carotídea se asocia a un
riesgo elevado de complicaciones, debido probablemente a
las importantes modificaciones fibrosas postoperatorias que
se producen en el tejido cervical y al hecho de que la reestenosis se deba con frecuencia a una hiperplasia de la mioíntima más que a la aterosclerosis53. Aunque en los pacientes sintomáticos con reestenosis, el efecto beneficioso a largo plazo
de la EDAC continúa justificando el riesgo quirúrgico inmediato y hace que sea inferior al riesgo del tratamiento médico
solo, la única evidencia derivada de estudios aleatorizados
sugiere que los pacientes asintomáticos con reestenosis evolucionan ligeramente mejor con el tratamiento médico1. Dado que la ACIS no requiere una incisión cervical ni arterial,
es probable que los factores anatómicos relacionados con el
sexo o con la EDAC previa sean superados por la ACIS. La
oclusión carotídea contralateral puede comprometer los mecanismos de compensación y, por consiguiente, la perfusión
cerebral durante el pinzamiento de la arteria carotídea que
es necesario para practicar la EDAC. La menor duración de
la oclusión carotídea durante la ACIS, en comparación con
la EDAC, podría explicar la ausencia de aumento del riesgo
operatorio durante la ACIS. En cambio, otros factores como
la edad, la hipertensión y los antecedentes de EC o EAC, tienen una intensa asociación con la gravedad y la extensión de
la aterosclerosis y es probable que estén relacionados con el
riesgo de complicaciones tromboembólicas durante el avance
arterial por la aorta y la arteria carótida.
Con el empleo de un análisis de metarregresión, observamos que los riesgos de la ACIS han disminuido a lo largo del
tiempo, entre 1993 y 2006. Esto puede ser consecuencia de
mejoras en la técnica de la ACIS, los dispositivos utilizados
o la formación de los especialistas, así como de una mejor
selección de los pacientes candidatos para la ACIS a lo largo
del tiempo. El desarrollo de dispositivos de protección frente
a la embolia durante la intervención de ACIS puede haber sido un avance importante. Las revisiones sistemáticas anteriores de series de casos sin asignación aleatoria indicaron que
el uso de los dispositivos de protección cerebral parece reducir las complicaciones tromboembólicas durante la ACIS54
y también la incidencia de nuevas lesiones isquémicas, mayoritariamente asintomáticas en la resonancia magnética con
ponderación de difusión obtenida en las primeras 48 horas
siguientes a la ACIS55,56. Nuestros resultados, obtenidos a
partir de un mayor número de estudios, concuerdan con estos
datos previos. Sin embargo, hubo una heterogeneidad significativa entre los distintos estudios en este análisis. De hecho,
la aparente ventaja de los dispositivos de protección cerebral
podría ser ilusoria. Ciertamente, el uso de estos dispositivos
de protección ha aumentado con el paso del tiempo, y el aparente efecto protector puede haberse visto afectado por los
efectos de confusión derivados de los avances en las técnicas
de implantación de stents y en la selección de los pacientes
a lo largo del tiempo. Podría reflejar también la selección de
los pacientes. Además, continúa sin haber datos de estudios
aleatorizados en los que se compare la ACIS con o sin protección cerebral, y puesto que los dispositivos de protección
deben superar la estenosis arterial, es posible que los propios
dispositivos pudieran causar complicaciones.
Nuestro estudio tiene varias posibles limitaciones. En primer lugar, la existencia de factores de confusión constituye
una amenaza importante en un metaanálisis de estudios observacionales, puesto que los análisis de subgrupos se basan
en comparaciones univariadas. Solamente un metaanálisis
de los datos individuales permitiría abordar esta cuestión.
Sin embargo, nuestros análisis de subgrupos fueron muy
uniformes en los diversos estudios y disponen de explicaciones fisiopatológicas plausibles. Además, con el empleo
de un enfoque similar para la EDAC, todos los factores de
riesgo para las complicaciones observadas en las revisiones
sistemáticas de los estudios de registros se reprodujeron en
un análisis combinado de los datos individuales de ECA16–
20,43. Así pues, es improbable que nuestros resultados sean
falsamente positivos. En segundo lugar, aunque incluimos
los estudios publicados en cualquier idioma y utilizamos
múltiples fuentes de datos, los sesgos de publicación podrían haber distorsionado nuestros resultados, puesto que
los registros con un riesgo de complicaciones bajo podrán
tener una mayor probabilidad de haber sido publicados. Sin
embargo, con el empleo de gráficos de dispersión de puntos
sencillos, puesto que no hay ninguna prueba estadística validada para valorar el sesgo de publicación en un metaanálisis de riesgos absolutos, no observamos indicio alguno de
sesgos de publicación. Además, los sesgos de publicación
son improbables en los análisis de subgrupos, dado que es
improbable que las posibilidades de publicación estén relacionadas con los resultados de los análisis de subgrupo, y
no observamos indicio alguno de sesgos de este tipo en los
gráficos de embudo. Por otra parte, los RR no suelen depender del riesgo absoluto. En tercer lugar, la posible inclusión
de datos duplicados podrían haber distorsionado nuestros
resultados57. Sin embargo, examinamos detalladamente la
relación de autores y el contexto de cada artículo con objeto
de excluir en la mayor medida posible las poblaciones duplicadas. Además, realizamos análisis de sensibilidad excluyendo algunos registros amplios que podrían haber incluido
a pacientes cuyos datos se hubieran publicado también en
estudios unicéntricos más pequeños, y los resultados obtenidos fueron similares. En cuarto lugar, la heterogeneidad
existente en la calidad de los datos constituye otro problema en los metaanálisis de estudios observacionales. Aunque
la calidad de la evaluación de las variables de valoración
fue diferente en los distintos estudios, nuestros resultados
no se vieron influidos por este parámetro. En quinto lugar,
algunos análisis de subgrupos (por ejemplo, tipo de episodio cerebrovascular, aspecto superficial de la placa o antecedentes de bypass arterial coronario) se basaron en un
número relativamente bajo de estudios y requerirían datos
de confirmación adicionales. Por último, hay otros posibles
factores de riesgo para las complicaciones que no pudieron
ser evaluados. Por ejemplo, el papel de la experiencia del
operador y la curva de aprendizaje no pudieron evaluarse en
nuestra revisión sistemática, puesto que no había una definición estandarizada de esos factores en los distintos estudios.
Es probable que los factores anatómicos arteriales influyan
también en la viabilidad y los riesgos de la ACIS58.
En resumen, los riesgos de la ACIS son globalmente superiores a los de la EDAC en los pacientes sintomáticos. Nuestros resultados respaldan la recomendación de las actuales
guías en cuanto a que la ACIS no debe utilizarse en los pacientes que son candidatos adecuados para el tratamiento quirúrgico. Sin embargo, también sugieren que existen factores
que es probable que faciliten la selección de los candidatos
adecuados para la ACIS en futuros ensayos y finalmente en
la práctica clínica.
Agradecimientos
Quisiéramos agradecer especialmente a Peter A. Ringleb y a los investigadores del SPACE que nos proporcionaran datos de subgrupos
no publicados de este ensayo. Damos las gracias a Marta Pasquini,
Enrico Floβmann, Kaori Floβmann, Hu Chau, Maria Koziak, Daniel Freddy, Didier Leys, Ghislain Nokam, Barish Turak y Suzanne
Vobecky por su ayuda en la extracción de los datos de artículos publicados en lenguas diferentes del francés y el inglés. Agradecemos
también a Bernard Beyssen y Olivier Naggara sus recomendaciones
sobre aspectos técnicos y a Isabelle Laurent su apoyo técnico.
Ninguna.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
Declaraciones de intereses
Bibliografía
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