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Volume 339 Number 20
·
1415
BENEFIT OF CAROTID ENDARTERECTOMY IN PATIENTS WITH SYMPTOMATIC MODERATE OR SEVERE STENOSIS
BENEFIT OF CAROTID ENDARTERECTOMY IN PATIENTS WITH SYMPTOMATIC
MODERATE OR SEVERE STENOSIS
H
ENRY
J.M. B
ARNETT
, M.D., D. W
AYNE
T
AYLOR
, M.A., M
ICHAEL
E
LIASZIW
, P
H
.D., A
LLAN
J. F
OX
, M.D.,
G
ARY
G. F
ERGUSON
, M.D., R. B
RIAN
H
AYNES
, M.D., R
ICHARD
N. R
ANKIN
, M.D., G. P
ATRICK
C
LAGETT
, M.D.,
V
LADIMIR
C. H
ACHINSKI
, M.D., D
AVID
L. S
ACKETT
, M.D., K
EVIN
E. T
HORPE
, M.M
ATH
.,
AND
H
EATHER
E. M
ELDRUM
, B.A.,
FOR
THE
N
ORTH
A
MERICAN
S
YMPTOMATIC
C
AROTID
E
NDARTERECTOMY
T
RIAL
C
OLLABORATORS
*
A
BSTRACT
Background
Previous studies have shown that ca-
rotid endarterectomy in patients with symptomatic se-
vere carotid stenosis (defined as stenosis of 70 to 99
percent of the luminal diameter) is beneficial up to two
years after the procedure. In this clinical trial, we as-
sessed the benefit of carotid endarterectomy in pa-
tients with symptomatic moderate stenosis, defined
as stenosis of less than 70 percent. We also studied the
durability of the benefit of endarterectomy in patients
with severe stenosis over eight years of follow-up.
Methods
Patients who had moderate carotid ste-
nosis and transient ischemic attacks or nondisabling
strokes on the same side as the stenosis (ipsilateral)
within 180 days before study entry were stratified ac-
cording to the degree of stenosis (50 to 69 percent or
<50 percent) and randomly assigned either to un-
dergo carotid endarterectomy (1108 patients) or to
receive medical care alone (1118 patients). The aver-
age follow-up was five years, and complete data on
outcome events were available for 99.7 percent of
the patients. The primary outcome event was any fa-
tal or nonfatal stroke ipsilateral to the stenosis for
which the patient underwent randomization.
Results
Among patients with stenosis of 50 to 69
percent, the five-year rate of any ipsilateral stroke
(failure rate) was 15.7 percent among patients treat-
ed surgically and 22.2 percent among those treated
medically (P=0.045); to prevent one ipsilateral stroke
during the five-year period, 15 patients would have
to be treated with carotid endarterectomy. Among
patients with less than 50 percent stenosis, the failure
rate was not significantly lower in the group treated
with endarterectomy (14.9 percent) than in the med-
ically treated group (18.7 percent, P=0.16). Among the
patients with severe stenosis who underwent endar-
terectomy, the 30-day rate of death or disabling ipsi-
lateral stroke persisting at 90 days was 2.1 percent;
this rate increased to only 6.7 percent at 8 years.
Benefit was greatest among men, patients with recent
stroke as the qualifying event, and patients with hemi-
spheric symptoms.
Conclusions
Endarterectomy in patients with symp-
tomatic moderate carotid stenosis of 50 to 69 percent
yielded only a moderate reduction in the risk of
stroke. Decisions about treatment for patients in this
category must take into account recognized risk fac-
tors, and exceptional surgical skill is obligatory if ca-
rotid endarterectomy is to be performed. Patients with
stenosis of less than 50 percent did not benefit from
surgery. Patients with severe stenosis (»70 percent)
had a durable benefit from endarterectomy at eight
years of follow-up. (N Engl J Med 1998;339:1415-25.)
©1998, Massachusetts Medical Society.
From the John P. Robarts Research Institute, London, Ont. (H.J.M.B.,
M.E., H.E.M.); the Department of Clinical Epidemiology and Biostatis-
tics, McMaster University, Hamilton, Ont. (D.W.T., R.B.H., K.E.T.); the
Departments of Clinical Epidemiology and Biostatistics (M.E.), Diagnostic
Radiology and Nuclear Medicine (A.J.F., R.N.R.), and Clinical Neurolog-
ical Sciences (H.J.M.B., A.J.F., G.G.F., V.C.H.), University of Western On-
tario, London; the Department of Surgery, University of Texas Southwest-
ern Medical Center, Dallas (G.P.C.); and the Nuffield Department of
Clinical Medicine, University of Oxford, Oxford, United Kingdom (D.L.S.).
Address reprint requests to Dr. Barnett at the John P. Robarts Research In-
stitute, P.O. Box 5015, 100 Perth Dr., London, ON N6A 5K8, Canada.
J. David Spence, M.D., Department of Clinical Neurological Sciences,
University of Western Ontario, London, was also an author.
*Other North American Symptomatic Carotid Endarterectomy Trial
(NASCET) Collaborators are listed in the Appendix.
N 1954 a patient with symptoms suggesting
that a stroke was imminent underwent success-
ful removal of a stenosed segment of the carotid
artery.
1
From that initial experience, carotid
endarterectomy evolved. In 1985 it was performed
107,000 times in the United States.
2
Two negative
randomized trials were reported.
3,4
On the basis of
anecdotal evidence, about 1 million endarterectomies
were performed worldwide between 1974 and 1985.
5,6
Reports of unacceptable rates of complications, re-
views of health care data bases, and editorials called
into question the benefit of endarterectomy.
7-13
The
failure of cerebral bypass surgery in a randomized
trial strengthened the opinion that data from case
series alone were inadequate as a guide to the use of
surgical therapy.
14
Three studies of endarterectomy
in patients with symptomatic carotid stenosis
15-17
were
intended to answer similar questions: How effica-
cious is endarterectomy as compared with medical
care alone? Which patients should be offered endar-
terectomy? What is the acceptable complication rate?
What bearing do risk factors have on benefit? How
durable are the benefits of endarterectomy? Do oth-
er causes of stroke confound the interpretation of
results?
In the North American Symptomatic Carotid End-
arterectomy Trial (NASCET), begun in 1987, we
stratified patients according to the degree of stenosis:
those with moderate stenosis, defined as less than 70
percent of the luminal diameter, and those with severe
stenosis, defined as stenosis of 70 to 99 percent. In
February 1991, after 659 patients with »70 percent
I
Copyright © 1998 Massachusetts Medical Society. All rights reserved.
Downloaded from www.nejm.org at VANDERBILT UNIVERSITY on October 25, 2005 .
1416
·
November 12, 1998
The New England Journal of Medicine
stenosis had undergone randomization at 50 centers,
the study in this stratum was stopped.
15,18
Endarter-
ectomy was found to be associated with an absolute
reduction of 17 percentage points (95 percent con-
fidence interval, 10 to 24) in the risk of ipsilateral
stroke at two years. Consequently, endarterectomy
was recommended for the patients with severe ste-
nosis who had been randomly assigned to medical
therapy.
Patients with moderate stenosis (<70 percent) con-
tinued to be enrolled. All patients with severe ste-
nosis (»70 percent) who were enrolled in the first
phase were followed until the trial concluded. This
report provides data on the outcomes of carotid
endarterectomy in patients with moderate stenosis,
enrolled from December 1987 through December
1996, and on the patients with severe stenosis who
were enrolled through February 1991.
METHODS
Details of our research methods have been published else-
where.
19
Patients with moderate carotid stenosis were enrolled at
106 centers and stratified according to the degree of stenosis:
high moderate (50 to 69 percent) or low moderate (<50 per-
cent). The primary research question was this: For patients with
moderate stenosis, is it better to perform endarterectomy imme-
diately or to give medical therapy and offer endarterectomy only
if stenosis progresses to 70 percent or more? Patients randomly
assigned to medical therapy whose stenoses progressed to 70 per-
cent or more, with symptoms, were offered endarterectomy.
Eligibility and Randomization
Patients over 80 years of age were excluded in the first phase
(the study of both moderate and severe stenosis through Febru-
ary 1991) but included in the second phase (the continuing study
of moderate stenosis). Patients were eligible if they had symptoms
of focal cerebral ischemia ipsilateral to a stenosis of less than 70
percent in the internal carotid artery within 180 days, as shown
on selective angiography, and persisting less than 24 hours or
producing a nondisabling stroke (Rankin score <3 with symp-
toms for 24 hours or more).
20
All angiograms were assessed at
the central office of the study with use of a magnifying eyepiece
to measure the severity of carotid stenosis.
19,21
Patients were ex-
cluded if they did not provide informed consent or if one or more
of the following were present: lack of angiographic visualization
of the symptomatic artery, intracranial stenosis that was more
clinically significant than the cervical lesion, other disease that
limited life expectancy to less than five years, cerebral infarction
that eliminated useful function in the affected arterial territory,
nonatherosclerotic carotid disease, cardiac lesions likely to cause
cardioembolism, or a history of ipsilateral endarterectomy.
Patients were randomly assigned to medical or surgical therapy
by means of a centralized computer-generated algorithm with strat-
ification according to center.
Treatment
Patients were prescribed antiplatelet treatment (usually aspirin,
with the dose left to the discretion of the neurologist at each study
center) and, when indicated, antihypertensive and antilipidemic
drugs. Surgical technique was left to the discretion of the individual
surgeons. Simultaneous vascular procedures were discouraged.
Follow-up
Neurologists assessed all patients at entry, at 1, 3, 6, 9, and 12
months, and every 4 months thereafter. Risk-factor management
was monitored in the study data center. Cross-sectional brain im-
aging was performed after suspected cerebrovascular events. Duplex
ultrasonography was repeated at one month, at intervals of one
year after study entry, and after cerebrovascular events. If endar-
terectomy appeared to be indicated by noninvasive studies, angi-
ography was repeated. Randomization ceased on December 15,
1996. Final assessments of patients took place between January 1
and December 15, 1997.
Events
We assessed the underlying cause of all deaths and the territory,
type, severity, and duration of strokes. Strokes were considered
disabling if patients had a Rankin score of 3 or more at 90 days.
Outcome events were assessed in four steps: first, by the partici-
pating neurologist and surgeon; second, by the neurologists at
the study data center; third, by the members of the steering com-
mittee, in a blinded manner; and fourth, by blinded external ad-
judicators. Lacunar strokes, as distinct from strokes of large-artery
origin, were defined on the basis of a combination of clinical and
radiologic criteria, as follows: events presenting with primary
motor, primary sensory, or sensory–motor symptoms, the dysar-
thria–clumsy hand syndrome, or the ataxia–hemiparesis syn-
drome, all with radiologically deep white-matter lesions or basal-
ganglia lesions <1 cm in diameter. The criteria for cardioembolic
stroke included atrial fibrillation, myocardial infarction and its
thrombotic or cardiac-wall sequelae, the need for cardiac inter-
ventional procedures, and the presence of valvular lesions. When
the diagnosis was unclear, consultation with a cardiologist, with
appropriate investigations, was requested.
Statistical Analysis
The primary intention-to-treat analysis compared medical and
surgical patients in terms of the time to treatment failure (defined
as a fatal or nonfatal ipsilateral stroke), with use of the Mantel–
Haenszel chi-square test and Kaplan–Meier survival curves.
22
The
benefit of endarterectomy was described in terms of relative and
absolute reductions in the risk of stroke and the number of pa-
tients who would need to be treated with endarterectomy for one
outcome event to be prevented within five years after the proce-
dure. Standard errors of the absolute risk reduction at five years
and 95 percent confidence intervals for the survival curves were
calculated with use of Greenwood’s formula.
22
In the primary
analysis, treatment failure was defined as any fatal or nonfatal
stroke ipsilateral to the carotid lesion. Secondary analyses included
the end points of all strokes, all deaths, and strokes according to
severity categories. All P values were two-tailed, and P values be-
low 0.05 were considered to indicate statistical significance.
The primary and secondary analyses included all strokes (at any
location) and all deaths (from any cause) that occurred during the
30-day postoperative period, or a 32-day period after randomiza-
tion in the case of patients assigned to medical therapy. Patients
discovered to be ineligible after randomization because they did
not have a qualifying carotid lesion or corresponding symptoms
were excluded from all analyses.
Risk factors for stroke and death in the 30 days after endarterec-
tomy were evaluated in logistic-regression analyses. In these analy-
ses, each of the base-line factors on which we obtained data was
considered. Only univariate results are presented in this article.
The influence of base-line risk factors in determining which pa-
tients benefited most from carotid endarterectomy was investigat-
ed with use of Cox proportional-hazards regression modeling.
22
To minimize the risk of chance findings and to increase the clin-
ical relevance of the results, risk factors were considered impor-
tant only if they differentiated between patients who benefited
from endarterectomy and those who did not with respect to both
any ipsilateral stroke and disabling ipsilateral stroke. Analyses of
event-free survival were used to estimate the number of patients
who would need to be treated in order to prevent one ipsilateral
stroke during the five years after the procedure, among patients
in various risk-factor categories.
Copyright © 1998 Massachusetts Medical Society. All rights reserved.
Downloaded from www.nejm.org at VANDERBILT UNIVERSITY on October 25, 2005 .
BENEFIT OF CAROTID ENDARTERECTOMY IN PATIENTS WITH SYMPTOMATIC MODERATE OR SEVERE STENOSIS
Volume 339 Number 20
·
1417
RESULTS
Accrual of Patients
A total of 2267 patients with stenosis of less than
70 percent were randomly assigned to treatment
groups. A review panel blinded to the treatment as-
signments excluded 41 patients (1.8 percent) because
they did not meet the entry criteria; 24 of the 41
underwent endarterectomy because the central an-
giographic review showed the stenosis to be greater
than 70 percent, 11 did not have angiographic evi-
dence of stenosis, 3 did not have a qualifying ischemic
event, 2 did not provide informed consent, and no
information was available after randomization for 1.
The remaining 2226 eligible patients (1118 assigned
to medical therapy and 1108 to surgical therapy)
were included in all analyses. The treatment groups
were well balanced in terms of base-line characteristics
(Table 1).
There were 858 eligible patients with 50 to 69
percent stenosis (428 in the medical-therapy group
and 430 in the surgical-therapy group); 1368 had ste-
nosis of less than 50 percent (690 in the medical-
therapy group and 678 in the surgical-therapy group).
Among the patients with low-moderate stenosis (<50
percent) there were 425 patients (213 in the medi-
cal-therapy group and 212 in the surgical-therapy
group) who were found to have stenosis of less than
30 percent after angiographic review. These patients
were included in all analyses reported here. Analyses
performed with and without these patients with so-
called mild stenosis did not differ significantly.
Follow-up
The average follow-up for all patients was five years.
Six patients (five in the surgical-therapy group and
one in the medical-therapy group) were lost to follow-
up after a median of 36 months. Complete data about
outcome events were available for 99.7 percent of the
patients. All 1818 surviving patients (911 in the
medical-therapy group and 907 in the surgical-thera-
py group) underwent final assessments during 1997.
Crossovers
Twenty-one (1.9 percent) of the 1108 patients
randomly assigned to surgery did not actually under-
go endarterectomy: 12 withdrew their consent, 6 had
medical complications, and the surgeons decided not
to perform endarterectomy in 3. All were followed
throughout the study and included in all analyses ex-
cept those involving the calculation of perioperative
morbidity and mortality.
In the medical-therapy group, 88 of 1118 patients
(7.9 percent) underwent endarterectomy, as specified
in the protocol, after the progression of stenosis to
70 percent or more was verified by angiography; an
additional 34 (3.0 percent) underwent endarterecto-
my after an ipsilateral stroke. Only 78 (7.0 percent)
*TIA denotes transient ischemic attack, CT computed to-
mography, MRI magnetic resonance imaging, and MI myo-
cardial infarction. There were no statistically significant dif-
ferences between the groups in any of the base-line variables.
T
ABLE
1.
B
ASE
-L
INE
C
HARACTERISTICS
OF
THE
P
ATIENTS
WITH
M
ODERATE
S
TENOSIS
,
A
CCORDING
TO
T
REATMENT
G
ROUP
.*
C
HARACTERISTIC
M
EDICAL
T
HERAPY
(N=1118)
S
URGICAL
T
HERAPY
(N=1108)
Median age (yr) 66 66
Age (%)
<65 yr
65–74 yr
»75 yr
36
47
17
41
45
14
Sex (%)
Male
Female
69
31
71
29
Race (%)
White
Black
Other
93
3
4
93
4
3
Qualifying event (%)
TIA (hemispheric)
Stroke (hemispheric)
TIA (retinal)
Stroke (retinal)
37
45
13
5
40
42
12
6
Randomized within 30 days of
event (%)
42 41
History of TIA or stroke (%) 55 54
Location of lesion (%)
Right-sided
Left-sided
46
54
47
53
Degree of ipsilateral stenosis (%)
50–69%
30–49%
<30%
38
43
19
39
42
19
Ipsilateral findings (%)
Ulcerated or irregular plaque
Intracranial disease
Lesion on CT or MRI
51
32
43
51
33
46
Contralateral lesion (%)
Occlusion
Ulceration
6
22
4
23
Diastolic blood pressure >90
mm Hg (%)
11 12
Systolic blood pressure >160
mm Hg (%)
19 20
History (%)
Prior MI or angina
Hypertension
Diabetes
Hyperlipidemia
Intermittent claudication
Current cigarette smoking
36
61
21
37
15
31
36
61
23
33
15
31
Medications (%)
Antithrombotic medication
Aspirin
None
<650 mg/day
»650 mg/day
Antihypertensive medication
Lipid-lowering medication
Cardiac medication
98
17
45
38
60
16
39
97
15
48
37
61
13
41
Copyright © 1998 Massachusetts Medical Society. All rights reserved.
Downloaded from www.nejm.org at VANDERBILT UNIVERSITY on October 25, 2005 .
1418
·
November 12, 1998
The New England Journal of Medicine
underwent endarterectomy not mandated by the pro-
tocol, often at the insistence of the patients or their
attending physicians. Censoring the data on these 78
patients at crossover had no effect on our conclusions.
Medical Treatment
The medical treatment prescribed was similar in
the two groups. The percentage of patients who were
prescribed antithrombotic medications (mostly aspi-
rin) was 96 to 99 percent in both groups throughout
the trial. At base line, 37 percent of the patients were
taking 650 mg or more of aspirin per day, and 11 per-
cent were taking less than 325 mg. At the final fol-
low-up evaluation, 31 percent were taking 650 mg or
more per day. Antihypertensive medications were tak-
en by 60 percent of the patients assigned to medical
therapy at base line and 61 percent of the patients as-
signed to surgery; this proportion rose to 68 percent
in both groups at the end of the study. Lipid-lowering
medications were prescribed for 16 percent of the pa-
tients in the medical-therapy group and 13 percent
of those in the surgical-therapy group at base line, a
proportion that rose to 40 percent in both groups.
Initially, cardiac medications were taken by 39 per-
cent of the medical-therapy group and 41 percent of
the surgical-therapy group; this proportion rose to
52 percent in both groups by the end of the study.
When blood pressure monitoring at the study data
center identified diastolic readings of 90 mm Hg or
more, systolic readings of 160 mm Hg or more, or
both, at two consecutive follow-up clinic visits, letters
went to the neurologists at the center where the pa-
tient was followed, alerting them to the patient’s hy-
pertension. The prevalence of hypertension declined
from 15 percent to 10 percent in both treatment
groups over the course of the trial.
23
Perioperative Morbidity and Mortality
A total of 1108 patients were randomly assigned to
endarterectomy; 21 of these received only medical
therapy, and endarterectomy was scheduled for 1087.
Between randomization and endarterectomy, one
retinal stroke occurred; there were no deaths. A me-
dian of two days elapsed between randomization
and endarterectomy. Endarterectomy was incomplete
in three patients.
In the 30 days after endarterectomy, 73 of the 1087
patients who underwent endarterectomy (6.7 percent)
had a stroke or died. Forty-three (4.0 percent) had a
nondisabling stroke (Rankin score, <3), 17 (1.6 per-
cent) had a nonfatal, disabling stroke (Rankin score,
»3), and 13 (1.2 percent) died (7 of stroke, 3 of
wound complications, 2 of myocardial infarction, and
1 suddenly on day 3). In the 32 days after randomiza-
tion, 27 medically treated patients (2.4 percent) had a
stroke or died; 1.4 percent had disabling stroke or
died. The net increase in risk at 30 days associated
with surgery was 4.3 percent for any stroke or death,
and 1.4 percent for disabling stroke or death. In eight
patients in the surgical-therapy group who had a
stroke, the severity decreased from disabling to non-
disabling by 90 days, yielding a rate of perioperative
disabling stroke and death of 2.0 percent.
Outcome Events
Table 2 shows the five-year risk of treatment failure,
defined according to six sets of criteria, for each cat-
egory of the severity of stenosis (50 to 69 percent
vs. <50 percent). For the primary analysis of any fa-
tal or nonfatal ipsilateral stroke, the five-year failure
rate for patients with 50 to 69 percent stenosis was
22.2 percent for medically treated patients and 15.7
percent for surgically treated patients (P=0.045).
The absolute difference of 6.5 percentage points cor-
responded to a relative risk reduction of 29 percent
(95 percent confidence interval, 7 to 52 percent); 15
patients would need to be treated by endarterectomy
to prevent one ipsilateral stroke at five years. For pa-
tients with stenosis of less than 50 percent, the cor-
responding five-year failure rates were 18.7 percent
for medically treated patients and 14.9 percent for
surgically treated patients (P=0.16).
This pattern persisted for all six definitions of
treatment failure. Patients with 50 to 69 percent ste-
nosis were at greater risk when treated medically,
and obtained a greater benefit from surgery, than
patients with stenosis of less than 50 percent.
Among patients with 50 to 69 percent stenosis, the
Mantel–Haenszel chi-square test was at or near sta-
tistical significance for all six definitions. It never ap-
proached significance for the patients with stenosis
of less than 50 percent.
Figure 1 shows the curves for event-free survival.
Among the patients enrolled who had stenosis of 70
percent or more, the 95 percent confidence intervals
for the curves remain separate at all times, whether
the outcome in question is stroke of any degree of
severity or disabling stroke. Among the patients with
50 to 69 percent stenosis, the confidence intervals
overlap slightly at all times. The overlap is greater for
disabling stroke than for any stroke. The confidence
intervals totally overlapped among the patients with
stenosis of less than 50 percent. The increasing over-
lap in the confidence intervals coincides with larger
P values, indicating decreasing significance.
Among patients treated surgically, the risk of ipsi-
lateral stroke dropped within 10 days after endarter-
ectomy to about 2 percent per year (Fig. 2). Among
medically treated patients, the risk of ipsilateral stroke,
which was highest immediately after the initial ische-
mic event, dropped more gradually to about 3 percent
per year within two to three years. This was true both
for patients with moderate stenosis (50 to 69 percent)
and for those with severe stenosis (70 to 99 percent).
Secondary analysis according to deciles of stenosis
did not show a gradient of benefit. The distribution
Copyright © 1998 Massachusetts Medical Society. All rights reserved.
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BENEFIT OF CAROTID ENDARTERECTOMY IN PATIENTS WITH SYMPTOMATIC MODERATE OR SEVERE STENOSIS
Volume 339 Number 20
·
1419
of deaths according to cause (Table 3) did not differ
significantly between the two treatment groups. The
territory and severity of first strokes are shown in Ta-
ble 4. The types of first ipsilateral stroke at five years
were similar in the two groups (Table 5). Lacunar
strokes made up 6.8 percent and 4.1 percent of the
events in the medical-therapy and surgical-therapy
groups, respectively; strokes of cardioembolic origin
accounted for 8.4 percent and 4.8 percent of the
events, respectively.
Risk Factors
A univariate analysis of all the base-line character-
istics listed in Table 1 identified seven characteristics
that doubled the perioperative risk of stroke or
death (P<0.05). These risk factors and the associat-
ed relative risk of any perioperative stroke or death
were contralateral carotid occlusion (relative risk,
2.3; 95 percent confidence interval, 1.1 to 5.1), left-
sided carotid disease (relative risk, 2.3; 95 percent
confidence interval, 1.4 to 3.8), taking less than 650
mg of aspirin per day (relative risk, 2.3; 95 percent
confidence interval, 1.3 to 3.9), the absence of a his-
tory of myocardial infarction or angina (relative risk,
2.2; 95 percent confidence interval, 1.3 to 3.8), a le-
sion present on computed tomography or magnetic
resonance imaging ipsilateral to the stenosed artery
for which the patient underwent randomization (rel-
ative risk, 2.0; 95 percent confidence interval, 1.2 to
3.1), a history of diabetes (relative risk, 2.0; 95 per-
cent confidence interval, 1.2 to 3.1), and diastolic
blood pressure above 90 mm Hg (relative risk, 2.0;
95 percent confidence interval, 1.1 to 3.3). Other
risk factors, including sex and age, were not statisti-
cally significant.
Cox regression analysis identified four characteris-
tics associated with greater long-term benefit of sur-
gery: male sex, a recent stroke, recent hemispheric
symptoms, and taking 650 mg or more of aspirin
per day. Among patients with stenosis of 50 to 69
percent, the number of patients who needed to be
treated with endarterectomy to prevent one ipsilat-
eral stroke of any degree of severity was 12 and the
number who needed to be treated to prevent one
*Events used to calculate the treatment-failure rate include all strokes (at any site) and all deaths from any cause between
randomization and the 30th day after surgery for surgically treated patients and during the 32-day period beginning with
randomization for medically treated patients.
†Plus–minus values are percent reductions ±SE. The negative number indicates an increase in risk.
‡P values are derived by comparison of the survival curves by the Mantel–Haenszel chi-square test.
§The number needed to treat is the number of patients who would have to be treated with endarterectomy for one
outcome event to be prevented at five years. For ipsilateral stroke at two years, the number needed to treat is 20 for
patients with stenosis of 50 to 69 percent and 48 for patients with stenosis of <50 percent. For patients with 70 to 99
percent stenosis, the number needed to treat is eight at both two and five years.
¶Failure rates, expressed as percentages, were derived from Kaplan–Meier estimates of survival at five years.
T
ABLE
2.
F
AILURE
R
ATES
AT
F
IVE
Y
EARS
OF
F
OLLOW
-
UP
, A
CCORDING
TO
THE
E
VENT
D
EFINING
T
REATMENT
F
AILURE
,
IN
P
ATIENTS
WITH
M
ODERATE
S
TENOSIS
.
E
VENT
D
EFINING
T
REATMENT
F
AILURE
*
M
EDICAL
T
HERAPY
S
URGICAL
T
HERAPY
R
ELATIVE
R
EDUCTION
IN
RISK
ABSOLUTE
REDUCTION
IN
RISK†
P
VALUE‡
N
UMBER
NEEDED
TO
TREAT§
no. of first events
(failure rate)¶ percent
Stenosis 50–69%
No. of patients 428 430
Any ipsilateral stroke 80 (22.2) 57 (15.7) 29 6.5±3.0 0.045 15
Disabling ipsilateral stroke 24 (7.2) 11 (2.8) 61 4.4±1.7 0.054 23
Any stroke 113 (32.3) 85 (23.9) 26 8.4±3.5 0.026 12
Any disabling stroke 34 (10.3) 20 (5.3) 49 5.0±2.1 0.070 20
Any stroke or death from any cause 156 (43.3) 120 (33.2) 23 10.1±3.8 0.005 10
Any disabling stroke or death from
any cause
86 (25.2) 64 (18.3) 27 6.9±3.2 0.032 14
Stenosis <50%
No. of patients 690 678
Any ipsilateral stroke 110 (18.7) 89 (14.9) 20 3.8±2.3 0.16 26
Disabling ipsilateral stroke 27 (4.7) 27 (4.6) 3 0.1±1.3 0.95 1000
Any stroke 151 (26.2) 148 (25.7) 2 0.5±2.7 0.88 200
Any disabling stroke 43 (8.0) 51 (8.7) — ¡0.7±1.7 0.56 —
Any stroke or death from any cause 209 (37.0) 208 (36.2) 2 0.8±3.0 0.97 125
Any disabling stroke or death from
any cause
113 (21.9) 120 (21.7) 1 0.2±2.6 0.70 500
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1420 · November 12, 1998
The New England Journal of Medicine
0.5
1.0
08
0.6
0.7
0.8
0.9
1 2 3 4 5 6 7
Year of Study
P=0.95
Disabling Ipsilateral Stroke, <50% Stenosis
NO. AT RISK
Surgical
therapy
Medical
therapy
78
79
641
661
553
562
443
465
349
350
279
245
190
167
138
119
Proportion without Events
0.5
1.0
08
0.6
0.7
0.8
0.9
1 2 3 4 5 6 7
Year of Study
P=0.16
Any Ipsilateral Stroke, <50% Stenosis
NO. AT RISK
Surgical
therapy
Medical
therapy
67
65
601
614
510
502
407
406
316
300
250
207
168
142
121
101
Proportion without Events
0.5
1.0
08
0.6
0.7
0.8
0.9
1 2 3 4 5 6 7
P=0.054
Disabling Ipsilateral Stroke, 50–69% Stenosis
NO. AT RISK
Surgical
therapy
Medical
therapy
61
51
391
396
340
338
284
280
229
224
187
173
145
133
95
92
Proportion without Events
0.5
1.0
08
0.6
0.7
0.8
0.9
1 2 3 4 5 6 7
P=0.045
Any Ipsilateral Stroke, 50–69% Stenosis
NO. AT RISK
Surgical
therapy
Medical
therapy
57
45
368
363
317
300
261
248
207
193
167
143
134
110
89
77
Proportion without Events
0.5
1.0
08
0.6
0.7
0.8
0.9
1 2 3 4 5 6 7
P=0.0043
Overlap of CI
Medical therapy
Surgical therapy
Disabling Ipsilateral Stroke, 70–99% Stenosis
NO. AT RISK
Surgical
therapy
Medical
therapy
122
93
314
305
307
290
297
272
284
258
268
244
247
229
192
183
Proportion without Events
0.5
1.0
08
0.6
0.7
0.8
0.9
1 2 3 4 5 6 7
P<0.001
Any Ipsilateral Stroke, 70–99% Stenosis
NO. AT RISK
Surgical
therapy
Medical
therapy
111
73
300
275
290
249
281
230
264
218
247
207
224
192
174
151
Proportion without Events
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BENEFIT OF CAROTID ENDARTERECTOMY IN PATIENTS WITH SYMPTOMATIC MODERATE OR SEVERE STENOSIS
Volume 339 Number 20 · 1421
Figure 1. Kaplan–Meier Curves for Event-free Survival among
Patients with Severe and Moderate Stenosis.
The curves show the probability of avoiding an ipsilateral
stroke of any degree of severity (left-hand panels) and a disab-
ling ipsilateral stroke (right-hand panels) among patients with
carotid stenosis of 70 to 99 percent (top), 50 to 69 percent (cen-
ter), and less than 50 percent (bottom) who were randomly
assigned to undergo carotid endarterectomy (surgical-therapy
group) or to receive medical therapy alone (medical-therapy
group). Also shown are the P values from the Mantel–Haenszel
chi-square test used to compare the survival curves, with the
95 percent confidence interval (CI) for each curve and the over-
lap between the confidence intervals indicated by bands of color.
The numbers below the panels are the numbers of patients in
each group who were still at risk during each year of follow-up.
These analyses were conducted according to the intention-to-
treat principle and include patients who crossed over to the oth-
er treatment. The survival curves for medically treated patients
differ significantly among the three severity-of-stenosis groups
(P=0.02 for all ipsilateral strokes and P<0.001 for disabling
ipsilateral strokes); the curves did not differ significantly for
surgically treated patients (P=0.58 and P=0.51, respectively).
disabling stroke was 16 for men; the corresponding
numbers were 67 and 125 for women, 10 and 13 for
patients with a recent stroke, 27 and 59 for those
with transient ischemic attacks as the qualifying event,
11 and 16 for patients with recent hemispheric symp-
toms (as compared with negative benefit for patients
with retinal symptoms only), 7 and 14 for patients
taking 650 mg or more of aspirin per day, and 125
and 44 for those taking less aspirin or none.
The lack of significant benefit among women may
be explained by their comparatively low risk of stroke.
Among patients with 50 to 69 percent stenosis, the
risk of any ipsilateral stroke at five years in the med-
ically treated group was 15 percent for women, as
compared with 25 percent for men. Endarterectomy
reduced this risk to 14 percent among women and
17 percent among men.
Long-Term Results among Patients with Severe Stenosis
The 326 patients with symptomatic stenosis of 70
percent or more who underwent endarterectomy
were followed for an average of eight years. Com-
plete data on outcome events were available for 98.8
percent; four patients were lost to late follow-up.
The Kaplan–Meier survival curves (Fig. 3) show the
risk of disabling ipsilateral stroke and stroke of any
severity in these patients from 30 days to 8 years.
DISCUSSION
Patients with symptomatic carotid stenosis of 70
percent or more (severe stenosis) derive a substantial
benefit from endarterectomy that persists for five
years or more. The benefit from the procedure is du-
rable. Patients with symptomatic moderate stenosis,
in the range of 50 to 69 percent, benefit less. The
overall significance of endarterectomy in preventing
ipsilateral stroke was marginal (P=0.045). The con-
fidence intervals overlapped in the survival curves at
every time point (Fig. 1); the number of such pa-
tients who would need to be treated in order to pre-
vent one additional stroke of any degree of severity
was double that for patients with stenosis of 70 per-
cent or more. Patients with stenosis of less than 50
percent did not benefit from endarterectomy.
The benefit of endarterectomy was apparent
among patients with moderate or severe stenosis
within the first two to three years after endarterec-
tomy (Fig. 2). Among medically treated patients, the
risk of ipsilateral stroke dropped dramatically to an
annual level similar to that among surgically treated
patients. If they have no recurring symptoms, pa-
tients have little to gain from endarterectomy after
two to three years.
The results of recent randomized trials of endar-
terectomy in patients with symptomatic lesions are in
broad agreement. The European Carotid Surgery
Trial (ECST),
24
which was similar to ours in size,
concluded that “carotid endarterectomy is indicated
...when the symptomatic stenosis is greater than
about 80 percent.” A stenosis of 80 percent as meas-
ured in ECST is equivalent to 60 percent stenosis
determined by the method we used. Our measure-
ments of 30, 40, 50, 60, 70, 80, and 90 percent ste-
nosis correspond to stenoses of 65, 70, 75, 80, 85,
91, and 97 percent, respectively, in ECST.
25,26
Angio-
graphic conversions are essential for the results of the
trials to be compared.
27
Caveats apply when our results are extrapolated to
the general population of patients with symptoms re-
lated to carotid disease. First, the surgeons who par-
ticipated in our trial were selected for their high level
of expertise. If the risk of disabling stroke and death
associated with endarterectomy exceeds the levels re-
ported here (2.0 percent), the small benefit of endar-
terectomy in patients with stenoses of 50 to 69 percent
is eliminated, resulting in no benefit. Carotid endar-
terectomy should be performed only at institutions
and by surgeons whose patients have low rates of com-
plications as determined by independent monitoring.
Second, these results do not apply when measure-
ments of stenosis are made with the narrowest por-
tion of the lumen used as the numerator and the ca-
rotid bulb or a segment of post-stenotic dilatation as
the denominator. Both methods overestimate the se-
verity of stenosis.
21
It is not clear that measurements
obtained by ultrasonography or other noninvasive
methods can be substituted for those based on angi-
ography.
28
Comparisons of noninvasive studies with
angiography must be carried out at individual centers
and the use of noninvasive studies validated before
angiography is discarded. Nonvalidated ultrasonog-
raphy frequently overestimates the degree of stenosis,
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1422 · November 12, 1998
The New England Journal of Medicine
Figure 2. Change in the Risk of Ipsilateral Stroke over Time, According to Severity of Stenosis and Treatment Group.
The curves show the risk of an ipsilateral stroke over the next year among patients who had not had an ipsilateral stroke
since randomization. Separate calculations were made every 10 days from randomization to the sixth year of follow-up
for patients with stenosis of 50 to 69 percent at base line (Panel A) and those with stenosis of 70 to 99 percent at base
line (Panel B).
0.00
0.18
0 6
0.02
0.04
0.06
0.08
0.10
0.12
0.14
0.16
1 2 3 4 5
Year of Study
70–99% Stenosis
B
Risk of Stroke in the Subsequent Year
0.00
0.18
0 6
0.02
0.04
0.06
0.08
0.10
0.12
0.14
0.16
1 2 3 4 5
Year of Study
50–69% Stenosis
Medical therapy
Surgical therapy
A
Risk of Stroke in the Subsequent Year
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BENEFIT OF CAROTID ENDARTERECTOMY IN PATIENTS WITH SYMPTOMATIC MODERATE OR SEVERE STENOSIS
Volume 339 Number 20 · 1423
suggesting erroneously that the lesion falls within the
range of stenosis known to benefit from endarterec-
tomy. Disabling stroke follows 0.1 percent of angio-
graphic studies; however, inappropriate carotid end-
arterectomy exposes patients to a 2.0 percent risk of
disabling stroke or death.
29
Third, although the results of post hoc analyses
must be interpreted with caution, base-line risk factors
appear to have an important effect on perioperative
and long-term outcomes after carotid endarterecto-
my. Supporting evidence from other large studies of
endarterectomy is required, although some confirm-
atory data are available.
30-35
Systematic comparisons
between the large endarterectomy data bases are now
being conducted.
All risk factors must be evaluated when patients
with 50 to 69 percent stenosis are being considered
for endarterectomy. Patients can be expected to
benefit if they have a high risk of stroke over the
next two to three years when treated medically and
if they are at low risk for stroke after endarterecto-
my. Observations from both our study and other
studies suggest that long-term benefit of surgery is
greater and the risk of stroke with medical treatment
is higher for men than for women, for patients who
have had stroke than for those with transient ischemic
attacks, and for patients with hemispheric symptoms
than for those with retinal symptoms. These obser-
vations also suggest that the risk of perioperative
stroke or death is increased in patients with diabetes,
elevated blood pressure, contralateral occlusion, left-
sided disease, or a lesion that is evident on computed
tomography or magnetic resonance imaging.
TABLE 4. TYPE AND SEVERITY OF FIRST STROKES
AFTER RANDOMIZATION AMONG PATIENTS WITH MODERATE
STENOSIS, ACCORDING TO TREATMENT GROUP.
TYPE OF STROKE
MEDICAL THERAPY
(N=1118)
S
URGICAL THERAPY
(N=1108)
NONDIS-
ABLING
DIS
-
ABLING FATAL
NONDIS
-
ABLING
DIS
-
ABLING FATAL
no. of patients
Ipsilateral hemispheric
stroke
126 33 6 94 18 7
Ipsilateral retinal stroke 21 0 0 14 0 0
Contralateral hemispheric
stroke
39 13 6 48 12 6
Contralateral retinal
stroke
700 500
Vertebrobasilar stroke 29 6 3 32 10 3
Subarachnoid hemorrhage 0 0 0 0 0 1
Total 222 52 15 193 40 17
*Values for events include all strokes (at any site) and deaths (from any
cause) during the 30 days after surgery for surgically treated patients and
during the 32 days after randomization for the medically treated patients.
†This category includes only deaths from causes other than stroke in the
30 days after endarterectomy for surgically treated patients and the 32 days
after randomization for the medically treated patients.
‡Computed tomography was not performed in these cases.
TABLE 5. TYPE OF FIRST IPSILATERAL STROKE OR OTHER EVENT
AT FIVE YEARS OF FOLLOW-UP IN PATIENTS WITH MODERATE
STENOSIS, ACCORDING TO TREATMENT GROUP.*
EVENT
MEDICAL
THERAPY
(N=1118)
S
URGICAL
THERAPY
(N=1108)
no. (%)
Large-artery hemispheric stroke
Nonhemorrhagic stroke
Hemorrhagic infarction
121 (63.7)
7 (3.7)
96 (65.8)
6 (4.1)
Large-artery retinal stroke 19 (10.0) 14 (9.6)
Subtotal of events originating in
carotid artery
147 (77.4) 116 (79.5)
Lacunar stroke 13 (6.8) 6 (4.1)
Cardioembolic stroke 16 (8.4) 7 (4.8)
Primary intracerebral or subarachnoid
hemorrhage
1 (0.5) 4 (2.7)
Death not due to stroke† 1 (0.5) 5 (3.4)
Subtotal of events not originating in
the carotid artery
31 (16.3) 22 (15.1)
Uncertain‡ 12 (6.3) 8 (5.5)
Total 190 (100.0) 146 (100.0)
TABLE 3. DEATHS AMONG PATIENTS WITH MODERATE STENOSIS,
ACCORDING TO CAUSE AND TREATMENT GROUP.
CAUSE OF DEATH
MEDICAL
THERAPY
(N=1118)
S
URGICAL
THERAPY
(N=1108)
no. of patients (%)
Stroke 24 30
Myocardial infarction 35 32
Other ischemic heart disease 36 34
Sudden death 17 23
Other cardiovascular disease 11 11
Cancer 45 33
Respiratory disease 23 10
Other cause 40 45
Total 231 (20.7) 218 (19.7)
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1424 · November 12, 1998
The New England Journal of Medicine
Enthusiasm for endarterectomy is increasing.
36
In
1996 the operation was performed 130,000 times in
the United States, a number double that in 1991
(Pokras RE, National Hospital Discharge Survey: per-
sonal communication).
37
Many patients with symp-
tomatic stenosis of less than 70 percent will not be
considered appropriate candidates for endarterectomy
when the risks and benefits are carefully weighed.
Our final results do not justify a large increase in the
rate of endarterectomy. We recommend restraint.
Supported by a grant (R01-NS-24456) from the National Institute of
Neurological Disorders and Stroke.
We are indebted to Drs. Michael Walker and John Marler of the
National Institute of Neurological Disorders and Stroke for their
wise counsel and ongoing support; to SmithKline Beecham for sup-
plying enteric-coated aspirin (Ecotrin) to all patients throughout the
trial; to the staff of the central data office for their dedicated work;
to the clinical coordinators in each participating center for their me-
ticulous work; and to Fern Livingstone and Cathy Wild for their
careful attention to the preparation of the manuscript.
APPENDIX
The following were participants in the NASCET, listed in descending
order of the number of patients enrolled with less than 70 percent stenosis:
London, Ont. — V.C. Hachinski, S. Patterson, C. Swan, G.G. Ferguson, S.
Lownie, H. Reichman, J.D. Spence, L. Paddock-Eliasziw, H.W.K. Barr,
K.A. Harris; Quebec City, Que. — D. Simard, B. Leger, C. Benguigui, A.
Lajeunesse, J.M. Bouchard, J. Cote, A. Mackey, D. Marois, C. Roberge,
J.F. Turcotte, E. Daigle, L. Lessard, Y. Douville, H.P. Noel; Toronto — F.L.
Silver, B. Huth, S. Slattery, J.R. Fleming, F. Gentili, P.M. Walker, M.C.
Wallace, J.W. Norris, B. Bowyer, M. Fazl, M.J. Gawel, D.W. Rowed; Rich-
mond, Va. — J. Harbison, N. Eubank, G. Clifton, W. Felton III, H.M. Lee,
P. Muizelaar, M. Sobel, J. Taylor; Marshfield, Wis. — P. Karanjia, C. Matti,
B.E. Brink, R.L. Kolts, M.E. Kuehner, K. Madden, M.K. Swanson; Hel-
sinki, Finland — M. Kaste, R. Lonnqvist, A. Jarvinen, R. Luosto; Ottawa,
Ont. — B.G. Benoit, A. MacIntyre, N. Pageau, A. Hakim, D. Preston, C.
Skinner; Saskatoon, Sask. — A. Kirk, A. Shuaib, C. Henry, C. Regier, B.
Bharadwaj, G. Goplen; Mississauga, Ont. — G. Sawa, G. Schiavinato, H.
Schutz; Vancouver, B.C. — P.A. Teal, V.P. Sweeney, C. Johnston, D. Cameron,
V. Devonshire, F.A. Durity, A.J. Salvian, D.C. Taylor; Portland, Oreg. — W.
Clark, K. Kearns, E. Radakovich-Harrison, D. Briley, G. Moneta, R. Yeager;
Tel Aviv, Israel — N. Bornstein, B. Aronovich, E. Shifrin; Dallas — G.P.
Clagett, C. Mathison, W. Bryan, D.H. Unwin, R.J. Valentine; Montreal —
R. Cote, F. Bourque, J.-L. Caron, L.H. Lebrun, M.-P. Desrochers, A. Bel-
lavance, L. Berger, P. Couillard, N. Daneault, P. Ghosn, G. Mohr; Minne-
apolis — J. Davenport, A.C. Klassen, C. Farmer, R. Maxwell, D. Wen; Leb-
anon, N.H. — A.G. Reeves, P.E. Orem, R. Harbaugh; Syracuse, N.Y. — A.
Culebras, M.T. Dean, C.J. Hodge, Jr.; Halifax, N.S. — C.W. McCormick,
J. McCormick, R.O. Holness, S.J. Phillips; Iowa City, Iowa — H.P. Adams,
L. Vining, J.D. Corson, P.H. Davis, C.M. Loftus; Little Rock, Ark. — S.M.
Nazarian, L.A. Kennedy, R.W. Barnes; Edmonton, Alta. — M.G. Elleker,
E. Hutchings, J.M. Findlay; Houston — J.C. Grotta, P. Bratina, D.B. Vital,
P.M. Shedden; Columbus, Ohio — A.P. Slivka, M.A. Notestine, W.L.
Smead, J.G. Wright; San Antonio, Tex. — D. Sherman, D. Rogers, O.
Benavente, R. Hart, M. Kanter-Carolin, W. Rogers, H.D. Root, D. Solo-
mon; Indianapolis — S. Lalka, B. Hughes, M. Dalsing; Los Angeles — W.S.
Moore, C. Donayre, S.N. Cohen, J. Frazee, M. Fisher, A. Mohammadi, S.F.
Figure 3. Kaplan–Meier Curves for Event-free Survival after Endarterectomy among 326 Patients with Severe Stenosis.
The curves show the probability of avoiding an event, according to four different definitions of an outcome event,
among patients with 70 to 99 percent stenosis who underwent carotid endarterectomy. Point estimates are shown for
the risk of each event at 30 days, 5 years, and 8 years after surgery. The risk of disabling ipsilateral stroke at 30 days
includes all perioperative deaths and disabling strokes. The risks of ipsilateral stroke, any stroke, and any stroke or death
include all perioperative deaths and all strokes of any type.
0.0
1.0
06
0.2
0.4
0.6
0.8
7 81 2 3 4 5
Years after Surgery
RISK OF EVENT (%)
Disabling ipsilateral stroke
Ipsilateral stroke
Any stroke
Any stroke or death
Disabling ipsilateral stroke
Ipsilateral stroke
Any stroke
Any stroke or death
2.1
5.8
5.8
5.8
5.1
13.0
22.3
31.0
6.7
15.2
29.4
46.6
Proportion without Events
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BENEFIT OF CAROTID ENDARTERECTOMY IN PATIENTS WITH SYMPTOMATIC MODERATE OR SEVERE STENOSIS
Volume 339 Number 20 · 1425
Ameriso, F.A. Weaver, A.E. Yellin; Winnipeg, Man. — B.A. Anderson, D.F.
Gladish, M. West; Memphis, Tenn. — C. Watridge, V. Bizzle, S. Erkulwater,
J.T. Robertson; Chicago — C. Helgason, V. Glover, J. DeBord, J. Schuler,
J.-P.C. Spire, B. Cohen, J. Biller, J. Yao, M.A. Kelly, M.J. Devalle; Calgary,
Alta. — K.M. Hoyte, M.E. Robertson, G.R. Sutherland; San Diego, Calif.
— C. Jackson, J. Rothrock, N. Kelly, R. Hye; Tucson, Ariz. — B.M. Coull,
W.M. Feinberg, D.C. Bruck, G.C. Hunter; Columbia, Mo. — H.H. White,
W. Hamilton, M.K. Gumerlock, J.J. Oro; Providence, R.I. — J.D. Easton,
J.-A. Sarafin, N. Knuckey; Sheffield, United Kingdom — G. Venables, C.
Doyle, J. Beard; Chicoutimi, Que. — M. Beaudry, D. Boivin; Tampere,
Finland — T. Kuurne, L. Eronen, J. Salenius; Phoenix, Ariz. — R.F. Spet-
zler, S.L. Hunsley, J.L. Frey; Miami — A. Forteza, R. Kelley, A. Living-
stone; Hines, Ill. — S.R. Gupta, J. Maggio, F.N. Littooy; Melbourne,
Australia — P. Gates, L. Rath, J. Gurry; Boston — P.A. Wolf, E. Licata-
Gehr, N.L. Cantelmo, J.O. Menzoian, S. Warach, C. Mayman, J.J. Skillman,
A. Ropper, S. Razvi; Tampa, Fla. — S. Zachariah, D. Bandyk; Bronx, N.Y.
— D.M. Rosenbaum, R.A. De Los Reyes, F. Veith; Oulu, Finland — M.
Hillbom, K. Ylonen; Kuopio, Finland — J. Sivenius, I. Oksala; St. Louis —
D.W. Thompson, C. Gomez, K.R. Smith, Jr.; Parkville, Australia — S.
Davis, P. Field, R. Gerraty; Jackson, Miss. — R.R. Smith; Pittsburgh — L.E.
Knepper, S. DeCesare, M. Webster; Dublin, Ireland — G. Shanik; Albu-
querque, N.M. — G.D. Graham, E.C. Benzel, A. Bruno; Madison, Wis. —
C. Acher, R. Levine; Cincinnati — R.E. Welling, R.L. Reed; Philadelphia
— R.H. Rosenwasser, D. Jamieson; Utrecht, the Netherlands — L.J. Kap-
pelle, B.C. Eikelboom; Hamilton, Ont. — R.J. Duke, J.D. Wells; Geelong,
Australia — P. Gates, I.B. Faris; Nedlands, Australia — W.M. Carroll; Lex-
ington, Ky. — B. Young. L.C. Pettigrew; Baltimore — C. Johnson, C.
Jones; Eau Claire, Wis. — R.A. Narotzky, A. Murrle; Perugia, Italy — S.
Ricci, P. Cao; Jerusalem, Israel — A. Reches, Y. Berlatzky; Petah Tikva, Israel
— J. Streifler, A. Zelikovski; Heidelberg, Australia — G.A. Donnan, J.P.
Royle; Minden, Germany — O. Busse, J. Gronniger; Haifa, Israel — S.
Torem; Hot Springs, Ark. — R.G. Pellegrino, J. Arthur; Allentown, Pa. —
J.E. Castaldo, J. McCullough; New York — J.P. Mohr, D.O. Quest, S. Jonas,
J. Jafar, D. Barbut; Buffalo, N.Y. — L.A. Hershey, G.R. Curl, I. Gutierrez,
P. Kinkel, J. Budny; St. John’s, Newf. — A. Goodridge; Lahti, Finland —
C. Hedman, H. Huusari; Gainesville, Fla. — J.M. Seeger; New Hyde Park,
N.Y. — R. Libman, J. Cohen; Worcester, Mass. — E. Arous; Daw Park,
Australia — R. Foreman; Sacramento, Calif. — J. Byer, A. Tajlil; Stockholm,
Sweden — N.G. Wahlgren; Des Moines, Iowa — L. Struck, D.H. Stubbs;
Detroit — S. Chaturvedi, F. Diaz; Perth, Australia — G. Hankey, M.
Goodman; Johannesburg, South Africa — V. Fritz, L. Levien; Wynnewood,
Pa. — M. Alter; Regina, Sask. — F. Veloso, C. Ekong; Omaha, Nebr. —
E.A. Waltke, A.P. Gasecki, T.G. Lynch; Rochester, N.Y. — C.G. Benesch, R.
Green; Schenectady, N.Y. — P.E. Spurgas; Albany, N.Y. — B.I. Tranmer.
Members of the Executive Committee, Writing Committee, Monitoring
Committee, and Adjudication Committee, representatives of the National
Institute of Neurological Disorders and Stroke, and management staff are
listed on our Web site (www.nascet.rri.on.ca).
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