Original Contribution
Carotid Stenting
Is There an Operator Effect? A Pooled Analysis From the Carotid
Stenting Trialists’ Collaboration
David Calvet, MD, PhD; Jean-Louis Mas, MD; Ale Algra, MD, PhD;
Jean-Pierre Becquemin, MD; Leo H. Bonati, MD, PhD; Joanna Dobson, MSc; Gustav Fraedrich, MD;
Olav Jansen, MD; Willem P. Mali, MD; Peter A. Ringleb, MD, PhD*;
Gilles Chatellier, MD, PhD*; Martin M. Brown, MD, FRCP*†
Downloaded from http://stroke.ahajournals.org/ by guest on June 14, 2017
Background and Purpose—Randomized clinical trials show higher 30-day risk of stroke or death after carotid artery
stenting compared with surgery. We examined whether operator experience is associated with 30-day risk of stroke or
death in the Carotid Stenting Trialists’ Collaboration database.
Methods—The Carotid Stenting Trialists’ Collaboration is a pooled individual patient database including all patients
recruited in 3 randomized trials of stenting versus endarterectomy for symptomatic carotid stenosis (Endarterectomy
Versus Angioplasty in patients with Symptomatic Severe Carotid Stenosis trial, Stent-Protected Angioplasty versus
Carotid Endarterectomy trial, and International Carotid Stenting Study). Lifetime carotid artery stenting experience,
lifetime experience in stenting procedures excluding the carotid, and annual number of procedures performed within
the trial (in-trial volume), divided into tertiles, were used to measure operator experience. The outcome event was the
occurrence of any stroke or death within 30 days of the procedure. The analysis was done per protocol.
Results—Among 1546 patients who underwent carotid artery stenting, 120 (7.8%) had a stroke or death within 30 days of the
procedure. The 30-day risk of stroke or death did not differ according to operator lifetime carotid artery stenting experience
(P=0.8) or operator lifetime stenting experience excluding the carotid (P=0.7). In contrast, the 30-day risk of stroke or
death was significantly higher in patients treated by operators with low (mean ≤3.2 procedures/y; risk 10.1%; adjusted risk
ratio=2.30 [1.36–3.87]) and intermediate annual in-trial volumes (3.2–5.6 procedures/y; 8.4%; adjusted risk ratio=1.93
[1.14–3.27]) compared with patients treated by high annual in-trial volume operators (>5.6 procedures/y; 5.1%).
Conclusions—Carotid stenting should only be performed by operators with annual procedure volume ≥6 cases per year. (Stroke. 2014;45:00-00.)
Key Words: carotid stenosis ◼ carotid stenting ◼ prevention
A
t present, randomized clinical trials in patients with
symptomatic carotid disease show inferior results of
stenting compared with surgery with regard to the risk of
stroke or death within 30 days of treatment, which was
mostly attributed to an excess of minor or nondisabling
stroke.1 To improve the risk–benefit profile of stenting, it is
crucial to establish which factors among patient characteristics and the procedure itself are associated with a high risk
of stroke after carotid stenting. The Carotid Stenting Trialists’
Collaboration (CSTC) pooled individual patient data from
the Endarterectomy Versus Angioplasty in patients with
Symptomatic Severe Carotid Stenosis trial (EVA-3S), the
Stent-Protected Angioplasty versus Carotid Endarterectomy
trial (SPACE), and the International Carotid Stenting Study
(ICSS). With this database, we recently showed that, compared
with surgery, the risks of stenting were higher in patients aged
≥70 years.1 Carotid stenting is a technically demanding procedure. However, the minimum volume requirements and training criteria for potential operators remain largely unknown.2–4
In the present study, we assessed whether operator lifetime
Received September 24, 2013; accepted November 3, 2013.
From the Department of Neurology, Hôpital Sainte-Anne, Université Paris Descartes, INSERM UMR894, Paris, France (D.C., J.-L.M.); Department
of Neurology and Julius Centre for Health Sciences and Patient Care (A.A.) and Department of Radiology (W.P.M.), University Medical Centre Utrecht,
Utrecht, The Netherlands; Department of Vascular Surgery, University Hospital Henri Mondor, Creteil, France (J.-P.B.); Department of Neurology and
Stroke Unit, University Hospital Basel, Basel, Switzerland (L.H.B.); Department of Brain Repair and Rehabilitation, Institute of Neurology, University
College London, London, United Kingdom (L.H.B., M.M.B.); Medical Statistics Unit, Department of Epidemiology and Population Health, London
School of Hygiene and Tropical Medicine, London, United Kingdom (J.D.); Department of Vascular Surgery, Medical University, Innsbruck, Austria (G.F.);
Department of Neuroradiology, Schleswig-Holstein University Hospital, Kiel, Germany (O.J.); Department of Neurology, University Hospital Heidelberg,
Heidelberg, Germany (P.A.R.); and Clinical Research Unit, Hôpital Européen Georges Pompidou, Université René Descartes, Paris, France (G.C.).
*Drs Ringleb, Chatellier, and Brown contributed equally.
†A list of all Carotid Stenting Trialists’ Collaboration participants is given in the Appendix.
Correspondence to Jean-Louis Mas, MD, Service de Neurologie, Hôpital Sainte-Anne, 1 rue Cabanis, 75674 Paris Cedex 14, France. E-mail
jl.mas@ch-sainte-anne
© 2013 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org
DOI: 10.1161/STROKEAHA.113.003526
1
2 Stroke February 2014
experience and annual in-trial operator volume were associated with 30-day risk of stroke or death.
Methods
Downloaded from http://stroke.ahajournals.org/ by guest on June 14, 2017
EVA-3S (NCT 00190398), SPACE (ISRCTN 57874028), and ICSS
(ISRCTN 25337470) were randomized clinical trials with blinded
outcome adjudication. In all 3 trials, patients with recently symptomatic moderate or severe carotid stenosis (≥50% reduction in the lumen diameter according to the method used in the North American
Symptomatic Carotid Endarterectomy Trial [NASCET]),5 who were
considered equally suited for either procedure, were randomly allocated to undergo treatment by stenting or endarterectomy.6–8 The
pooled analysis of individual patient data was prospectively agreed
at the design stage of these trials.9 Details about experience required
to join the trials and procedure supervision methods are shown in
Table 1.
We assessed different variables of interest that are related to operator experience. The operator lifetime carotid artery stenting (CAS)
experience was defined for each procedure as the total number of
CAS procedures performed by each operator, including those performed before entering the trial and those performed within the trial
at the time of the procedure. The in-trial operator volume was defined
as the total number of CAS procedures performed in the trial by each
operator. The annual in-trial operator volume was calculated by dividing the in-trial operator volume by the number of years between
the first in-trial procedure and the end of the trial. In the SPACE trial,
operator experience before joining the trial was not recorded in absolute numbers of procedures but was available in categories of 10 to
24 or ≥25 CAS procedures. We also assessed the operator lifetime experience in stenting procedures excluding the carotid before entering
the trials. The outcome event for the present analysis was the combination of any stroke or death occurring within 30 days after treatment.
Statistical Analysis
The analysis was done per protocol, including only those patients
who received the randomly allocated CAS treatment as the first initiated revascularization procedure. Operator lifetime CAS experience,
operator lifetime stenting experience excluding the carotid, and annual in-trial operator volume were divided into tertiles. Operator
lifetime CAS experience was also categorized into 3 strata: <10, 10
to 24, and ≥25 to take SPACE data into account. The associations
Table 1. CAS Operator Criteria Required to Join Trials
Study
Operator Qualification
Required to Join Study*
If Operator Criteria Nonfulfilled
≥12 CAS (or ≥30
stenting procedures in
the supraaortic trunks
including ≥5 CAS)†
Supervision by an experienced tutor
(fulfilling criteria) until self-sufficient
and required criteria to join study
SPACE
≥25 CAS (bifurcation or
siphon)
Preliminary certificate if 10≤CAS<25,
but procedures performed under
guidance of a local experience
colleague‡
ICSS
≥50 stenting procedures
including ≥10 CAS
Outside proctor until 20 cases within
trial with acceptable results for proctor
and credential committee
EVA-3S
of lifetime operator experience and in-trial annual operator volume
with occurrence of stroke or death within 30 days of treatment were
assessed by crude risk ratios as calculated with Poisson regression
using the highest tertile of in-trial annual operator volume and the
highest tertile of operator lifetime experience as references.
To assess whether operators with 1 or 2 bad outcomes early in the
trial withdrew (or put in fewer patients subsequently), we divided
each operator period of participation (time between the first in-trial
procedure and the end of the trial) into 3 equal periods and calculated
for each operator the ratio of the number of patients treated during the
first period of participation in the trial to the number of those treated
during the second and third periods of participation. We compared
operators who treated ≥1 patient who had a bad outcome (30-day
stroke or death) during the first period of the study with those without
any complication during the first period. We also compared operators
who treated ≥2 patients who had a bad outcome during the first period
of the study with operators who had <2 complications. The nonparametric Mann–Whitney U test was used to compare those ratios.
We performed a multivariate analysis adjusting the crude effect
­estimates for the following potential predictors of 30-day risk of
stroke or death after stroke: age, sex, hypertension, history of coronary artery disease, contralateral severe carotid stenosis or carotid
­occlusion, use of cerebral protection devices, stent design (open- versus closed-cell stent), and source trial. These potential explanatory
variables were selected on the basis of the results of the CSTC preplanned meta-analysis of individual patient data,1 a previous analysis
of SPACE trial,10 a subgroup analysis of the Carotid Revascularization
Endarterectomy versus Stenting Trial (CREST),11 and our previous
review of literature.12
To account for the inherent clustering within data (the same operator performs multiple procedures over time), we also constructed
models using the framework of multilevel modeling with random intercepts included for individual operators.13 All 3 trials put into place
schemes allowing operators who did not fulfill the required number
of procedures to treat patients in the trial under the supervision of an
experienced peer, as specified in Table 1. In the present analysis, these
procedures were termed supervised. We compared outcomes between
supervised procedures and procedures performed by operators meeting the full experience criteria. In addition, we compared outcomes
across 3 successive periods of the trials (each including one third of
patients) to assess a potential learning curve during the trials as a
whole. In ICSS, monitoring of adverse events showed that 5 major
strokes (disabling of fatal strokes) of a total of 26 (19%) came from 2
operators who treated only 11 patients. These operators were stopped
from treating additional patients.9 We conducted a sensitivity analysis
excluding the data from the 2 operators concerned. Statistical analysis
was performed using SAS version 9.3 (SAS Institute, Inc, Cary, NC).
CAS indicates carotid artery stenting; EVA-3S, Endarterectomy Versus
Angioplasty in patients with Symptomatic Severe Carotid Stenosis trial; ICSS,
International Carotid Stenting Study; and SPACE, Stent-Protected Angioplasty
versus Carotid Endarterectomy trial.
*Documented proof of procedures performed before beginning of the trials
were used to assess previous experience. This had to be signed off by a
credential committee.
†No operator joined the trial based on this criterion.
‡Amendment of the study protocol in 2002.
Results
The pooled CSTC per-protocol analysis included 1679
patients who underwent CAS as their randomly allocated
revascularization procedure. Baseline characteristics of
patients are presented in Table 2. Absolute numbers of lifetimes CAS procedures and lifetime stenting procedures
excluding the carotid were available in 235 (90.4%) and 256
(98.5%) of 260 procedures, respectively, in EVA-3S and in
601 (72.6%) and 537 (64.9%), respectively, in ICSS. From
the SPACE trial, it was known whether the operator had performed 10 to 24 or ≥24 CAS before the trial for 586 (99.2%)
procedures. Details on annual in-trial operator volume were
available in 1546 (92.1%) of 1679 procedures. The median
(interquartile range) operator lifetime experience was 27 CAS
procedures (13–46) and 100 (50–300) stenting procedures
excluding the carotid. The median annual in-trial operator volume was 4.3 procedures (2.4–7.0) with tertiles of ≤3.2, 3.2 to
5.6, and >5.6 procedures. Stenting procedures were performed
Calvet et al Operator Effect in Carotid Artery Stenting 3
Table 2. Characteristics of Patients Treated With Carotid
Artery Stenting
Age at randomization, mean (SD), y
Age ≥70 y
Men
History of diabetes mellitus
History of hypertension
Systolic blood pressure at randomization, mean
(SD), mm Hg*
History of hypercholesterolemia†
Any smoking history (current or past)
69.4 (9.0)
828/1679 (49.3%)
1200/1679 (71.5%)
Table 3. Classification of Patients Into Tertiles of
Operator Experience, Annual In-Trial Operator Volume, and
Characteristics of Procedures
Lifetime operator experience
No. of CAS procedures at the time of the procedure*
391/1669 (23.4%)
Tertile 1 (0–16)
279/836 (33.4%)
1204/1669 (72.1%)
Tertile 2 (17–37)
270/836 (32.3%)
Tertile 3 (>37)
287/836 (34.3%)
144.8 (21.2)
No. of CAS procedures before the beginning of the trials†
661/1078 (61.3%)
1072/1669 (64.2%)
<10
292/1422 (20.5%)
10 to 24
294/1422 (20.7%)
836/1422 (58.8%)
History of coronary heart disease
401/1669 (24%)
≥25
History of peripheral artery disease†
173/1078 (16%)
No. of stenting procedure excluding the carotid*
Downloaded from http://stroke.ahajournals.org/ by guest on June 14, 2017
Type of most recent ipsilateral ischemic event before randomization
Tertile 1 (0–50)
317/793 (40%)
Retinal ischemia
303/1667 (18.2%)
Tertile 2 (51–224)
212/793 (26.7%)
Transient ischemic attack
572/1667 (34.3%)
Tertile 3 (>224)
264/793 (33.3%)
Hemispheric stroke
792/1667 (47.5%)
Annual in-trial operator CAS volume
History of stroke before most recent event†
184/1088 (24%)
Tertiles 1 (≤3.2)
506/1546 (32.7%)
Treatment within 14 d of most recent event‡
372/1434 (25.9%)
Tertiles 2 (3.2–5.6)
488/1546 (31.6%)
Tertiles 3 (>5.6)
552/1546 (35.7%)
Use of cerebral protection device‡
966/1662 (57.9%)
Supervised procedure
251/1679 (14.9%)
Days elapsed between most recent event and
treatment, median (IQR)‡
29 (14–65)
Score of the modified Rankin scale at baseline§
0
805/1663 (48.4%)
1
449/1663 (27.0%)
2
286/1663 (17.2%)
3
105/1663 (6.3%)
4
17/1663 (1.0%)
5
1/1663 (0.1%)
Degree of ipsilateral carotid stenosis
Moderate (50%–69%)
Severe (70%–99%)
Contralateral severe carotid stenosis (≥70%)
or occlusion
323/1679 (19.2%)
1356/1679 (80.8%)
232/1534 (15.1%)
Data are n/N (%), unless otherwise indicated. Percentages exclude missing
data (N=number of patients for whom data were available). IQR indicates
interquartile range.
*Rounded to nearest 5 mm Hg because of digit preference.
†Data were not gathered in the Stent-Protected Angioplasty versus Carotid
Endartectomy (SPACE) trial.
‡Date of the most recent ipsilateral ischemic event before randomization was
not gathered in the SPACE trial initially, but for meta-analysis these dates (or
if the exact date was not known, whether or not treatment and randomization
took place within 24 d of the qualifying event) were gathered where available.
§Modified Rankin scores at baseline might indicate nonstroke impairments;
protocols of contributing trials excluded patients with disabling strokes.
under supervision in 101 (38.8%) of 260 patients in EVA-3S,
51 (8.6%) of 591 in SPACE, and 99 (12.0%) of 828 in ICSS.
CAS procedures were performed by a single operator in 60%
of centers and by 2 operators in 26% of centers. The classification of patients into tertiles of (1) operator lifetime experience
in CAS procedures, (2) operator lifetime experience in stenting procedures excluding the carotid, and (3) annual in-trial
operator volume is shown in Table 3. There was no significant
difference in baseline variables potentially influencing procedural risks between patients treated by operators of different
Data are n/N (%), unless otherwise indicated. Percentages exclude missing
data (N=number of patients for whom data were available). CAS indicates
carotid artery stenting; and CSTS, Carotid Stenting Trialists’ Collaboration.
*Data were not gathered in the Stent-Protected Angioplasty versus Carotid
Endartectomy (SPACE) trial.
†Including patients enrolled in SPACE.
‡The number of procedures with use of cerebral protection device slightly
differs from first CSTC published data (additional available data).
lifetime CAS experience or annual in-trial operator volumes:
age, sex, hypertension, history of coronary artery disease, and
contralateral carotid occlusion (Table 4).
Cerebral protection devices were used in 966 (57.9%) of
1662 procedures. Among 1679 patients who underwent CAS,
130 (7.7%) had a stroke or died within 30 days of the procedure. The risk of 30-day stroke or death was 7.8% in the 1546
patients who had available data on annual in-trial operator volume. The 30-day risk of stroke or death did not differ according
to operator lifetime CAS experience (Table 5), classified into
tertiles or into 3 arbitrary categories (<10, 10–24, and ≥25) to
include SPACE data (Table 5). In contrast, the 30-day risk of
stroke or death was significantly higher in patients treated by
operators with low (10.1%; risk ratio [RR]=1.99 [1.27–3.10])
and intermediate annual in-trial volumes (8.4%; adjusted
RR=1.66 [1.04–2.64]) compared with patients treated by high
annual in-trial volume operators (5.1%; Table 5).
Annual in-trial operator volume was correlated neither with
operator lifetime CAS experience before the beginning of the
trials (P=0.29) nor with operator lifetime experience in stenting
procedures excluding the carotid (P=0.32). As expected, annual
in-trial operator volume was correlated with operator lifetime
CAS experience, including procedures performed during trials (P=0.01). The ratio of the number of patients treated during the first period of operator participation in the trial to the
number of those treated during the second and third periods of
4 Stroke February 2014
Table 4. Tertiles of Lifetime CAS Experience and Annual In-Trial Operator CAS Volume According to Potential Baseline Predictors
of CAS Risk
No. of CAS Procedures at the Time of the Procedure
Age ≥70 y
Women
History of hypertension
Annual In-Trial Operator CAS Volume
Tertile 1 (0–16)
Tertile 2 (17–37)
Tertile 3 (>37)
Tertile 1 (≤3.2)
Tertile 2 (3.2–5.6)
Tertile 3 (>5.6)
138 (49.5%)
144 (53.3%)
158 (55.1%)
246 (48.6%)
236 (48.4%)
277 (50.2%)
86 (30.8%)
79 (29.3%)
89 (31%)
146 (28.9%)
140 (28.7%)
162 (29.3%)
195 (70.9%)
184 (68.4%)
210 (73.9%)
364 (72.7%)
355 (72.9%)
392 (71.3%)
History of coronary heart disease
68 (24.7%)
62 (23.0%)
83 (29.2%)
125 (25.0%)
112 (23.0%)
124 (22.5%)
Contralateral severe carotid stenosis
(≥70%) or carotid occlusion
43 (15.5%)
52 (19.3%)
47 (16.5%)
71 (15.5%)
75 (17%)
64 (12.7%)
CAS indicates carotid artery stenting.
Downloaded from http://stroke.ahajournals.org/ by guest on June 14, 2017
operator participation did not differ in operators who had 1 or 2
bad outcomes early (P=0.78 and 0.94, respectively) compared
with operators without any complication during the first period.
The 30-day risk of stroke or death did not differ according
to whether procedures were supervised (RR=1.03 [0.65–1.63]
versus nonsupervised). Compared with patients treated in the
Table 5. Ratios and Risk Factor for Any Stroke or Death
Occurring Within 30 Days After Treatment According to
Lifetime Operator Experience, Annual In-Trial Operator CAS
Volume, and Characteristics of Procedures
Any Stroke or Death Within 30 d
Events n (%)/Total
Crude RR (95% CI)
Lifetime operator experience
No. of CAS procedures at the time of the procedure
first period of the trial, the 30-day risk of stroke or death did
not decrease in those treated in the second (RR=0.92 [0.61–
1.40]) and third periods (RR=1.09 [0.73–1.62]) of the trials.
After adjustment for potential predictors of 30-day risk of
stroke or death (see Methods section), the relative effects of
CAS were even stronger in patients treated by operators with
low (adjusted RR=2.30 [1.36–3.87]) and intermediate annual
in-trial volumes (adjusted RR=(1.93 [1.14–3.27]) compared
with patients treated by high annual in-trial volume operators.
Results of multivariate analyses were similar whether conventional models or multilevel models were used (data not
shown). Results of univariate and multivariate analyses were
not modified after exclusion of procedures performed under
supervision or exclusion of procedures performed by the 2
ICSS operators who were stopped after monitoring of adverse
events (data not shown).
Tertile 3 (>37)
26 (9.1%)/287
1
Tertile 2 (17–37)
20 (7.4%)/270
0.82 (0.47–1.43)
Discussion
Tertile 1 (0–16)
22 (7.9%)/279
0.87 (0.51–1.50)
In this pooled analysis of individual patient data from the
European-based randomized clinical trials of stenting versus
endarterectomy for symptomatic carotid stenosis, we showed
that the 30-day risk of stroke or death was lower (5.1%) in
patients treated by operators with the highest annual in-trial
volume compared with patients treated by operators with the
intermediate (8.4%) or lowest annual in-trial volume (10.1%).
In contrast, the operator lifetime experience was not associated with the 30-day risk of stroke or death.
Only a few studies have addressed the relationship
between operator experience and complications after
CAS.14–19 In agreement with our results, none of them
showed an association between lifetime operator experience and the 30-day risk of complications after CAS.14,15
In the lead-in phase of CREST, neither years of experience
in performing carotid intervention nor the number of CAS
procedures performed before the CREST lead-in phase was
associated with 30-day risk of stroke, myocardial infarction,
and death.14 In the Carotid Acculink/Accunet Post Approval
Trial to Uncover Rare Events (CAPTURE), a multicenter,
prospective postmarket registry, there was no difference
in the 30-day risk of stroke or death according to operator
lifetime experience as defined by combining stenting experience whatever the location and previous experience in performing carotid angiograms.15
With regard to the relationship between in-study volume
(which can be regarded as a measure of annualized rate of
No. of CAS procedures before the beginning of the trials
≥25
61 (7.3%)/836
1
10–24
25 (8.5%)/294
1.17 (0.75–1.82)
<10
26 (8.9%)/292
1.22 (0.79–1.89)
No. of stenting procedure excluding the carotid
Tertile 3 (>224)
25 (9.5%)/264
1
Tertile 2 (51–224)
18 (8.5%)/212
0.90 (0.50–1.60)
Tertile 1 (0–50)
24 (7.6%)/317
0.80 (0.47–1.37)
Annual in-trial operator CAS volume
Tertile 3 (>5.6)
28 (5.1%)/552
1
Tertile 2 (3.2–5.6)
41 (8.4%)/488
1.66 (1.04–2.64)
Tertile 1 (≤3.2)
51 (10.1%)/506
1.99 (1.27–3.10)
Periods of trial
First period
43 (7.7%)/557
1
Second period
40 (7.1%)/562
0.92 (0.61–1.40)
Third period
47 (8.4%)/560
1.09 (0.73–1.62)
Use of cerebral protection device
Yes
81 (8.4%)/966
1
No
48 (6.9%)/696
0.82 (0.58–1.16)
Supervision of procedure
Not supervised
Supervised
110 (7.7%)/1428
1
20 (8.0%)/251
1.03 (0.65–1.63)
CAS indicates carotid artery stenting; and CI, confidence interval.
Calvet et al Operator Effect in Carotid Artery Stenting 5
Downloaded from http://stroke.ahajournals.org/ by guest on June 14, 2017
CAS procedures during the study) and CAS complications,
most previous studies support our findings. In the CAPTURE
2 study, a prospective, nonrandomized, multicenter clinical
study that enrolled high–surgical-risk patients, an inverse
relationship was found between the 30-day risk of stroke,
myocardial infarction, and death and operator in-study volume.17 Among 24 701 patients identified in US Medicare
data on patients who underwent carotid stenting by 2339
operators, patients treated by low-volume operators (<6 procedures per year) had a higher risk of 30-day mortality at
2.5% compared with those treated by high-volume operators
(≥24 procedures per year) at 1.4%, independently of operator experience at the time of the procedure.16 In the SPACE
study, a decrease in 30-day ipsilateral stroke or death rate was
observed with increasing total numbers of patient enrollment
per center.19 In contrast, the 30-day risk of stroke, death, or
myocardial infarction did not differ according to the total
number of procedures performed in the CREST lead-in
phase.14 However, in the CREST study, operators with the
highest experience before the lead-in phase performed less
CAS procedures during the lead-in phase than those with the
least experience.
Finally, our results on the effect of a learning curve on
CAS outcomes differed from those of 2 previous studies.16,18
In a retrospective analysis of 182 consecutive patients who
had 200 CAS during a 40-month period at Baylor College
of Medicine–affiliated hospitals, the 30-day risk of stroke or
death decreased in the 3 latter sequential groups of 50 consecutive procedures compared with the first group.18 In the study
assessing the 30-day mortality after CAS in US Medicare
data (see above), patients treated early (first to 11th procedure) during a new operator’s experience (operators who first
performed CAS within the 3-year study period) had a higher
30-day mortality compared with those treated late (12th procedure or higher).16 In contrast to CREST,20 in our study, the
30-day risk of stroke or death did not decrease in 3 successive
periods of the trials that each included one third of patients,
suggesting the absence of learning curve. However, because
carotid stenting was a relatively new procedure at the beginning of the trials, CSTC trials were designed to avoid or limit
the effect of a learning curve. To join the trials, CSTC operators had to show proof of a previous experience in CAS or
were supervised.
Our study has potential limitations. First, our results apply
only to symptomatic carotid stenosis. Second, we did not take
into account CAS procedures performed by study investigators outside trials during the study period. Focusing on in-trial
volume could have provided potential underestimation of
CAS volume during the study period. However, even if this
would have led to misclassification of some operators in terms
of experience, it is unlikely that misclassification would differ
between operators with low or high complication rates, particularly in those with low in-trial volume.
Third, we cannot exclude that operators who had early bad
outcomes on the trial withdrew or put in fewer patients subsequently. However, such a bias is unlikely because there was
no difference in the evolution of the individual rate of CAS
procedures during the trial between operators who had 1 or 2
bad outcomes early compared with those who did not.
Finally, a potential selection bias linked to unequal distribution of potential risk factors between tertiles of annual in-trial
volume is possible in theory albeit unlikely because tertiles did
not differ according to potential covariates of CAS outcomes.
Our study shows that contrary to lifetime experience at the
time of procedure, interventionists who performed ≥6 CAS
procedures every year had better outcomes than those performing fewer numbers. We, therefore, conclude that carotid
stenting should only be performed at centers where interventionists can achieve this rate of CAS procedures. This adds
to the conclusion of our previously published analysis that
suggested that it would be reasonable to offer stenting as an
alternative option to endarterectomy to patients aged <65 to
70 years with symptomatic carotid stenosis in centers in which
acceptable periprocedural outcomes have been independently
verified.1
Appendix
Carotid Stenting Trialists’ Collaboration (CSTC)—Writing
Committee: D. Calvet (Department of Neurology, Hôpital
Sainte-Anne, Université Paris Descartes, INSERM UMR894,
Paris, France), J.-L. Mas (Department of Neurology, Hôpital
Sainte-Anne, Université Paris Descartes, INSERM UMR894,
Paris, France), A. Algra (Department of Neurology and Julius
Centre for Health Sciences and Patient Care, University Medical
Centre Utrecht, Utrecht, The Netherlands), J.-P. Becquemin
(Department of Vascular Surgery, University Hospital Henri
Mondor, 94010 Creteil, France), L.H. Bonati (Department
of Neurology and Stroke Unit, University Hospital Basel,
Basel, Switzerland; and Department of Brain Repair and
Rehabilitation, Institute of Neurology, University College
London, London, United Kingdom), J. Dobson (Medical
Statistics Unit, Department of Epidemiology and Population
Health, London School of Hygiene and Tropical Medicine,
London, United Kingdom), G. Fraedrich (Department of
Vascular Surgery, Medical University, Innsbruck, Austria), O.
Jansen (Department of Neuroradiology, Schleswig-Holstein
University Hospital, Kiel, Germany), W.P. Mali (Department
of Radiology, University Medical Centre Utrecht, Utrecht,
The Netherlands), P.A. Ringleb (Department of Neurology,
University Hospital Heidelberg, Heidelberg, Germany),
G. Chatellier (Clinical Research Unit, Hôpital Européen
Georges Pompidou, Université René Descartes, Paris,
France), M.M. Brown (Department of Brain Repair and
Rehabilitation, Institute of Neurology, University College
London, London, United Kingdom). Steering Committee:
A. Algra (independent chair); EVA-3S: J.P. Becquemin, G.
Chatellier, J.-L. Mas; SPACE: G. Fraedrich, P.A. Ringleb,
O. Jansen; ICSS: L. H. Bonati, M.M. Brown, W.P. Mali.
Steering Committees of trials included in CSTC: EVA-3S:
J.-L. Mas (chair), G. Chatellier (co-chair), J.-P. Becquemin,
J.-F. Bonneville, A. Branchereau, D. Crochet, J.C. Gaux, V.
Larrue, D. Leys, J. Watelet; SPACE: W. Hacke (chair), M.
Hennerici, J.R. Allenberg, P.C. Maurer, H.-H. Eckstein, H.
Zeumer, O. Jansen; ICSS: A. Algra, J. Bamford (chair), J.
Beard, M. Bland, A.W. Bradbury, M.M. Brown (chief investigator), A. Clifton, P. Gaines, W. Hacke, A. Halliday, I. Malik,
J.-L. Mas, A.J. McGuire, P. Sidhu, G. Venables.
6 Stroke February 2014
Sources of Funding
Downloaded from http://stroke.ahajournals.org/ by guest on June 14, 2017
The meta-analysis by the Carotid Stenting Trialists’ Collaboration was
funded by a grant from The Stroke Association. The Endarterectomy
Versus Angioplasty in patients with Symptomatic Severe Carotid
Stenosis trial (EVA-3S) trial was funded by a grant from the
Programme Hospitalier de Recherche Clinique of the French Ministry
of Health, Assistance Publique–Hôpitaux de Paris. The StentProtected Angioplasty versus Carotid Endarterectomy trial (SPACE)
trial was funded by grants from the Federal Ministry of Education and
Research, Germany, the German Research Foundation, the German
Society of Neurology, the German Society of Neuroradiology
(German Radiological Society), Boston Scientific, Guidant, and
Sanofi-Aventis. International Carotid Stenting Study (ICSS) was
funded by grants from the Medical Research Council, The Stroke
Association, Sanofi -Synthélabo, and the European Union. Dr Bonati
was supported by grants from the Swiss National Science Foundation
(PBBSB-116873), University of Basel, Switzerland, and The Stroke
Association. Dr Brown’s Chair in Stroke Medicine at University
College London is supported by the Reta Lila Weston Trust for
Medical Research. Part of this work was undertaken at University
College London Hospital/University College London, which received
a proportion of funding from the Department of Health’s National
Institute of Health Research Biomedical Research Centres funding
scheme.
Disclosures
None.
References
1. Bonati LH, Dobson J, Algra A, Branchereau A, Chatellier G, Fraedrich
G, et al. Short-term outcome after stenting versus endarterectomy for
symptomatic carotid stenosis: a preplanned meta-analysis of individual
patient data. Lancet. 2010;376:1062–1073.
2. Rosenfield K, Babb JD, Cates CU, Cowley MJ, Feldman T, Gallagher
A, et al. Clinical competence statement on carotid stenting: training
and credentialing for carotid stenting–multispecialty consensus recommendations: a report of the SCAI/SVMB/SVS Writing Committee to
develop a clinical competence statement on carotid interventions. J Am
Coll Cardiol. 2005;45:165–174.
3. Connors JJ III, Sacks D, Furlan AJ, Selman WR, Russell EJ, Stieg PE,
et al. Training, competency, and credentialing standards for diagnostic
cervicocerebral angiography, carotid stenting, and cerebrovascular intervention: a joint statement from the American Academy of Neurology,
the American Association of Neurological Surgeons, the American
Society of Interventional and Therapeutic Neuroradiology, the American
Society of Neuroradiology, the Congress of Neurological Surgeons, the
AANS/CNS Cerebrovascular Section, and the Society of Interventional
Radiology. Neurology. 2005;64:190–198.
4. Bates ER, Babb JD, Casey DE Jr, Cates CU, Duckwiler GR, Feldman
TE et al. ACCF/SCAI/SVMB/SIR/ASITN 2007 clinical expert consensus document on carotid stenting: a report of the American College
of Cardiology Foundation Task Force on Clinical Expert Consensus
Documents
(ACCF/SCAI/SVMB/SIR/ASITN
Clinical
Expert
Consensus Document Committee on Carotid Stenting). J Am Coll
Cardiol. 2007;49:126–170.
5. Naylor AR, Rothwell PM, Bell PR. Overview of the principal results and
secondary analyses from the European and North American randomised
trials of endarterectomy for symptomatic carotid stenosis. Eur J Vasc
Endovasc Surg. 2003;26:115–129.
6.Featherstone RL, Brown MM, Coward LJ; ICSS Investigators.
International carotid stenting study: protocol for a randomised clinical
trial comparing carotid stenting with endarterectomy in symptomatic
carotid artery stenosis. Cerebrovasc Dis. 2004;18:69–74.
7.Mas JL, Chatellier G, Beyssen B; EVA-3S Investigators. Carotid
angioplasty and stenting with and without cerebral protection: clinical alert from the Endarterectomy Versus Angioplasty in Patients
With Symptomatic Severe Carotid Stenosis (EVA-3S) trial. Stroke.
2004;35:e18–e20.
8. Ringleb PA, Kunze A, Allenberg JR, Hennerici MG, Jansen O, Maurer
PC, et al; Steering Committee of the SPACE Study. The Stent-Supported
Percutaneous Angioplasty of the Carotid Artery vs. Endarterectomy
Trial. Cerebrovasc Dis. 2004;18:66–68.
9. Ederle J, Dobson J, Featherstone RL, Bonati LH, van der Worp HB, de
Borst GJ, et al. Carotid artery stenting compared with endarterectomy
in patients with symptomatic carotid stenosis (International Carotid
Stenting Study): an interim analysis of a randomised controlled trial.
Lancet. 2010;375:985–997.
10. Jansen O, Fiehler J, Hartmann M, Brückmann H. Protection or nonprotection in carotid stent angioplasty: the influence of interventional techniques on outcome data from the SPACE Trial. Stroke. 2009;40:841–846.
11. Howard VJ, Lutsep HL, Mackey A, Demaerschalk BM, Sam AD II,
Gonzales NR, et al; CREST Investigators. Influence of sex on outcomes
of stenting versus endarterectomy: a subgroup analysis of the Carotid
Revascularization Endarterectomy versus Stenting Trial (CREST).
Lancet Neurol. 2011;10:530–537.
12. Touzé E, Trinquart L, Chatellier G, Mas JL. Systematic review of the
perioperative risks of stroke or death after carotid angioplasty and stenting. Stroke. 2009;40:e683–e693.
13. Urbach DR, Austin PC. Conventional models overestimate the statistical
significance of volume-outcome associations, compared with multilevel
models. J Clin Epidemiol. 2005;58:391–400.
14. Hopkins LN, Roubin GS, Chakhtoura EY, Gray WA, Ferguson RD,
Katzen BT, et al. The Carotid Revascularization Endarterectomy versus Stenting Trial: credentialing of interventionalists and final results of
lead-in phase. J Stroke Cerebrovasc Dis. 2010;19:153–162.
15. Gray WA, Yadav JS, Verta P, Scicli A, Fairman R, Wholey M, et al.
The CAPTURE Registry: results of carotid stenting with embolic
protection in the post approval setting. Catheter Cardiovasc Interv.
2007;69:341–348.
16. Nallamothu BK, Gurm HS, Ting HH, Goodney PP, Rogers MA, Curtis
JP, et al. Operator experience and carotid stenting outcomes in Medicare
beneficiaries. JAMA. 2011;306:1338–1343.
17. Gray WA, Rosenfield KA, Jaff MR, Chaturvedi S, Peng L, Verta P;
CAPTURE 2 Investigators and Executive Committee. Influence of site
and operator characteristics on carotid artery stent outcomes: analysis
of the CAPTURE 2 (Carotid ACCULINK/ACCUNET Post Approval
Trial to Uncover Rare Events) clinical study. JACC Cardiovasc Interv.
2011;4:235–246.
18. Lin PH, Bush RL, Peden EK, Zhou W, Guerrero M, Henao EA, et al.
Carotid artery stenting with neuroprotection: assessing the learning
curve and treatment outcome. Am J Surg. 2005;190:850–857.
19. Fiehler J, Jansen O, Berger J, Eckstein HH, Ringleb PA, Stingele R.
Differences in complication rates among the centres in the SPACE study.
Neuroradiology. 2008;50:1049–1053.
20. Gray WA, Simonton CA, Verta P. Overview of the 2011 Food and
Drug Administration Circulatory System Devices Panel meeting on the
ACCULINK and ACCUNET Carotid Artery Stent System. Circulation.
2012;125:2256–2264.
Carotid Stenting: Is There an Operator Effect? A Pooled Analysis From the Carotid
Stenting Trialists' Collaboration
David Calvet, Jean-Louis Mas, Ale Algra, Jean-Pierre Becquemin, Leo H. Bonati, Joanna
Dobson, Gustav Fraedrich, Olav Jansen, Willem P. Mali, Peter A. Ringleb, Gilles Chatellier and
Martin M. Brown
Downloaded from http://stroke.ahajournals.org/ by guest on June 14, 2017
Stroke. published online December 17, 2013;
Stroke is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 2013 American Heart Association, Inc. All rights reserved.
Print ISSN: 0039-2499. Online ISSN: 1524-4628
The online version of this article, along with updated information and services, is located on the
World Wide Web at:
http://stroke.ahajournals.org/content/early/2013/12/17/STROKEAHA.113.003526
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published
in Stroke can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office.
Once the online version of the published article for which permission is being requested is located, click
Request Permissions in the middle column of the Web page under Services. Further information about this
process is available in the Permissions and Rights Question and Answer document.
Reprints: Information about reprints can be found online at:
http://www.lww.com/reprints
Subscriptions: Information about subscribing to Stroke is online at:
http://stroke.ahajournals.org//subscriptions/