(Stroke. 1997;28:891-898.)
© 1997 American Heart Association, Inc.
Articles |
From the Division of Neurosurgery, Department of Surgery (J.H.W., J.M.F.), and the Department of Public Health Sciences (M.E.S.-A.), MacKenzie Health Sciences Centre, University of Alberta, Edmonton, Canada.
Correspondence to J.M. Findlay, Division of Neurosurgery, Department of Surgery, 2D1.02 MacKenzie Health Sciences Centre, University of Alberta, 8440-112 St, Edmonton, AB, Canada, T6G 2B7. E-mail jmfind{at}planet.eon.net
| Abstract |
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Methods Using health records, we retrospectively
reviewed 291 consecutive CEAs performed in our region over 18 months.
Based on randomized controlled trial results and standardized
remeasurements of angiographic carotid stenoses, indications
for CEA were considered appropriate for symptomatic carotid
stenoses
70%, uncertain for <70% symptomatic
or
60% asymptomatic stenoses, or inappropriate
for <60% asymptomatic stenoses and for patients
with preoperative neurological or medical instability.
Results We found that 41% of patients (118/291) were asymptomatic. Surgical indications were appropriate in 33% of cases (92/281), uncertain in 49% (138/281), and inappropriate in 18% (51/281). Stroke or death occurred within 30 days postoperatively in 5.2% (9/174) of symptomatic patients and 5.1% (6/117) of asymptomatic patients. At least one cardiac complication (angina, congestive heart failure, dysrhythmia, or myocardial infarction) developed in 8.9% (26/291). Independent preoperative risk factors for stroke or death were histories of angina or congestive heart failure and lack of antiplatelet medication; for cardiac complications, risk factors were age >75 years and a history of congestive heart failure.
Conclusions Almost 1 in 5 patients underwent CEA inappropriately, which was most commonly due to apparent overestimation of stenosis severity, and half had uncertain indications. Our high complication rate possibly negated any overall surgical benefit in the large group of asymptomatic patients.
Key Words: carotid endarterectomy complications health services misuse risk factors
| Introduction |
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Using the results of the recently reported randomized trials examining CEA as guidelines, the goal of this study was to determine the appropriateness and complication rates of all CEAs performed in our city over a recent 18-month period. Part of this analysis required an assessment of the accuracy of preoperative ultrasonography and angiography practiced in our region. We also wished to determine any risk factors in our patient population that were significantly predictive of postoperative stroke or death and cardiac complications.
| Subjects and Methods |
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Carotid angiograms were remeasured in a standardized fashion by one investigator (J.H.W.) who was blinded to patient identity and the original reported degree of stenosis. Angiograms that were difficult to interpret were evaluated in consultation with the senior author (J.M.F.) in a similar blinded manner. The angiographic method of measurement used was that of NASCET, ie, comparing the greatest degree of linear diameter stenosis of the ICA at the carotid bifurcation to the diameter of the distal normal ICA.15 These results were compared with the angiographic percentage of stenosis appearing on the original radiologist's report and the reported range of stenosis determined by ultrasonography. The presence or mention of an angiographic flow-limiting critical stenosis resulting in the appearance of a distally thin ICA, or a delay in contrast filling of the ICA compared with the adjacent external carotid artery, was classified as a 95% stenosis.16 Carotid bifurcation plaques were graded according to their angiographic appearance as being ulcerated, irregular, or smooth.17 The distal ipsilateral cerebral vasculature was assessed for arterial stenosis, defined as narrowing >50% of the local luminal diameter. Ultrasonography data were collected from the actual ultrasound report as obtained from the in-hospital record or referring diagnostic facility. No attempt was made in this study to establish standards of ultrasonographic equipment or technique. Angiography or ultrasonography reports using only subjective descriptors such as "severe" to quantify carotid stenosis were excluded from comparison analyses.
The appropriateness of operative indications was determined on the
basis of a review of five recent randomized controlled trials examining
CEA9 10 11 12 13 and clinical practice guidelines established by
both the American Heart Association18 and the Canadian
Neurosurgical Society (cerebrovascular writing group for the Canadian
Neurosurgical Society).18A With use of these criteria in
conjunction with our NASCET remeasurement values, the appropriateness
of CEA for each patient examined in this study was classified into one
of the following categories: (1) appropriate for
symptomatic patients with isolated and surgically
accessible carotid stenoses
70%, (2) uncertain for patients
with either symptomatic stenoses of <70% or
asymptomatic stenoses
60%, or (3) inappropriate
for patients with asymptomatic stenoses of <60%
and for those patients with significant neurological instability or
high-risk medical conditions. Preoperative neurological instability,
based on criteria as originally described by Sundt et al19
and more recently validated in a retrospective study,20
was defined as a progressing neurological deficit or a neurological
deficit within 1 day before CEA. High-risk preoperative medical
conditions were defined as unstable angina (defined as angina
developing at rest or of new onset), myocardial infarction within 3
months before CEA, or uncontrolled CHF. Patients were considered
symptomatic from their carotid disease if there was a
documented history of any prior cerebral or retinal ischemia
referable to the vascular territory of the stenotic carotid
artery (ie, ipsilateral transient ischemic attack, stroke,
amaurosis fugax, or retinal infarction). Patients with nonhemispheric
or nonretinal symptoms, such as dizziness, syncope, or bilateral visual
difficulties, were regarded as being asymptomatic from
their carotid disease.
The primary outcome event in this analysis was stroke or death occurring within 30 days of surgery. Any hemispheric neurological deficit lasting more than 24 hours was classified as a stroke. A major stroke was defined as one producing a significant functional deficit. For example, a patient rendered incapable of independent activities of daily living or requiring further rehabilitation was classified as having a major deficit, whereas mild weakness in a patient otherwise capable of independent ambulation and returning home on discharge was classified as a minor stroke. The degree of clinical recovery after hospital discharge was not assessed. A secondary outcome event was the development of at least one postoperative in-hospital cardiac complication (namely, angina, CHF, dysrhythmia, or myocardial infarction).
Data were collected using a computer database (FileMaker Pro 2.1,
Claris Corp) and analyzed with statistical software (SPSS 6.1,
SPSS Inc). Results were expressed as mean±SEM. The pooled
chance-corrected measure of agreement between the original
interpretation and the NASCET remeasurement value of the angiograms was
expressed as a
summary statistic. Univariate testing
used
2 and Fisher's exact tests for comparison
of proportions. Measures of association between risk factors and
outcome events were expressed as odds ratios with 95% CI. Level of
significance was set at P
.05, and all tests were
two-tailed. The associations between risk factors and outcome events
were also evaluated with multivariate analyses
using logistic regression models. Dependent variables were the
dichotomous outcomes of stroke or death and cardiac complications.
Independent variables used in these models included those listed in
Table 5
, as well as the following dichotomous variables: history of
diabetes mellitus, history of claudication, history of valvular
heart disease, preoperative neurological instability (present or
absent),19 20 preoperative systolic blood pressure
(>160 mm Hg or
160 mm Hg), carotid plaque irregularity
(present or absent),17 carotid plaque ulceration
(present or absent),17 intraoperative shunting (yes or
no), surgical service (neurosurgical or nonneurosurgical), and
postoperative bradycardia (<60 or
60 beats per minute). A stepwise
procedure was used to include variables in the model using values
of P
.05 for variable inclusion and P
.10
for exclusion.
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| Results |
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All patients had undergone carotid or cerebral angiography before
surgery, and 97% (281/291) of cases had angiograms available for
remeasurement. For this analysis, comparisons were made with
respect to each artery (both operated and nonoperated) rather than per
patient. Thirty arteries were excluded because the original radiologist
did not numerically quantify the degree of stenosis narrowing.
When the angiographic stenoses on both operated and nonoperated
sides were remeasured with the NASCET method, there was an overall
moderate agreement with the original radiologist's interpretation
(symptomatic stenosis:
=0.72 and 95% CI, 0.64
to 0.80; asymptomatic stenosis:
=0.67 and 95%
CI, 0.57 to 0.77) (see Table 2
). The method of
angiographic measurement used by the original radiologist could not be
reliably determined in this study.
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Stenoses on ultrasonography in our region are reported in
percentage ranges rather than specific values. Of the 248 patients who
underwent carotid ultrasonography as the initial diagnostic
test, 219 had ultrasonography reports available for review (88%), and
214 had both ultrasonographic and angiographic studies examined (86%).
Ultrasonographic accuracy was investigated per artery (both operated
and nonoperated) rather than per patient. After reports that did not
quantify carotid disease were excluded, 392 arteries were left for
analysis. As shown in Table 3
, preoperative
ultrasonography generally had a high sensitivity (89% and 97%) but
only moderate specificity (58% and 67%) for carotid disease of
50%
and
80%, respectively.
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With our criteria of appropriateness in conjunction with the NASCET
remeasurement values, the appropriateness of CEA was determined for our
patient population; the results are summarized in Table 4
. Appropriate indications for CEA were found in 33% of
patients (92/281), whereas 49% had indications considered uncertain
(138/281), and inappropriate surgical indications were found in 18% of
patients (51/281). Of the 51 cases with inappropriate indications, 23
(45%) were asymptomatic patients who were originally
incorrectly measured as having
60% stenosis, 14 (27%) were
asymptomatic patients who underwent surgery despite
stenoses correctly measured at <60%, 8 (16%) were patients
with preoperative neurological instability, and 6 (12%) were patients
at high preoperative medical risk. Recognizing the marked benefit of
CEA for severe symptomatic disease that was found in
NASCET9 and therefore the possible tendency to
operate on patients with stenoses that approached this degree
of narrowing, we reanalyzed the data using modified criteria by
which symptomatic stenoses
65% were considered
appropriate for CEA. However, this only minimally increased the
proportion of appropriate indications to 37% (104/281) and decreased
uncertain indications to 45% (126/281).
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Inappropriate use of CEA was found to vary widely among individual
surgeons, ranging from 0% to 33% (P=.07, df=8,
2 test). Of CEAs performed by the neurosurgical
service, 14% were classified as inappropriate versus 21%
inappropriate CEAs for the nonneurosurgical services, a difference that
was not statistically significant (P=.15,
2 test). Uncertain indications for CEA were found
in 33% to 67% of individual surgeons' series (P=.26,
df=8,
2 test). When stratified
according to surgical service, neurosurgeons used CEA for uncertain
indications significantly less often than their surgical colleagues
(40% versus 55%, P=.006,
2
test).
Overall, in this series there were six major strokes and five minor
postoperative strokes occurring within 30 days of surgery. (Two
additional minor strokes that developed as a result of angiography in
previously asymptomatic patients were not included in the
outcome analysis.) All strokes that occurred in this study were
ischemic, and all were in the territory of the operated carotid
artery. Of the four deaths that occurred in this series, two were due
to myocardial infarction, one was due to ischemic bowel
secondary to cardiovascular causes, and one was due to
interstitial pneumonitis. The combined stroke or death rate
in this series was 5.2±1.7% for symptomatic patients
(9/174) and 5.1±2.0% for asymptomatic patients (6/117).
Although a broad range of stroke or death rates for individual surgeons
was observed (0% to 33%), the relatively small number of operations
performed by the large number of surgeons in this analysis may
have contributed to an inability to statistically associate stroke or
death rates to individual surgeons (P=.22, df=8,
2 test) or to surgical specialty. The combined
stroke or death rate was 4.1% for neurosurgery and 5.9% for all other
surgical specialties combined (P=.49,
2 test).
Significant risk factors for stroke or death were determined by
univariate analysis and multiple logistic
regression and are summarized in Tables 5
and 6
. Independent preoperative risk factors for stroke or
death by multivariate analysis were a history
of angina, a history of CHF, and lack of preoperative antiplatelet
medication. At least one cardiac complication developed in 8.9% of
patients (26/291). The risk factors for cardiac complications,
determined by univariate and multivariate
analyses, are also summarized in Tables 5
and 6
. Multiple
logistic regression yielded age >75 years and a history of CHF as
being significant independent variables associated with cardiac
complications.
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| Discussion |
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On a smaller scale, Asaph and colleagues22 found that in a retrospective community surgical audit of 243 patients from 1986 through 1987, 37% of CEA patients underwent surgery for <80% asymptomatic stenosis. After these results were publicized, a local surgical committee formulated the following appropriate indications for CEA: carotid lesions causing transient ischemic attack or reversible ischemic neurological deficit, "significant" carotid stenoses causing stroke with subsequent recovery, asymptomatic carotid stenoses >80%, or any other reason if supported by a disinterested third party. As a result, over the succeeding 21 months, there was a drop in the number of operations performed, the surgical complication rate, and the number of "inappropriate" operations for asymptomatic carotid disease.
Such concerns over the appropriateness of CEA, along with its unproven
efficacy and possible excessive use,1 2 3 resulted in the
initiation of a number of randomized controlled CEA trials, including
NASCET,9 ECST,10 the symptomatic
and asymptomatic American Veterans Affairs
trials,11 12 and ACAS.13 The published
results of these studies have supplied evidence to support different
indications for CEA with correspondingly variable degrees of
certainty, and they have also provided benchmarks for acceptable
complication rates associated with each indication (Table 7
). Although NASCET and ECST measured carotid
stenosis in different ways, the preliminary results of both
indicate that CEA is much more effective than medical therapy in
preventing stroke for severe symptomatic stenoses,
providing that the perioperative stroke or death rate
is <6%.18 Surgery for patients with
symptomatic stenoses <70% was designated an
uncertain indication for CEA in our analysis, since NASCET had
not yet completed comparing CEA with medical therapy for such patients
during our study period and manuscript preparation. Because NASCET
specifically excluded patients with progressing or disabling
neurological deficits and those with uncontrolled medical illness, and
because previous studies have suggested that patients with these risk
factors have a high risk of postoperative stroke,19 20 in
our review patients with these features were considered inappropriate
candidates for surgery.
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Asymptomatic stenosis >60% (as determined by the NASCET method) was classified as an uncertain indication for CEA in our analysis. The only randomized controlled study to date indicating efficacy of CEA for stroke prevention in asymptomatic patients is ACAS, and the results of that study require careful interpretation.13 Although this trial demonstrated that the risk of stroke or death was significantly lowered in the surgical group, the absolute risk reduction with CEA was only slightly more than 1% per year projected over 5 years. As well, major strokes were not prevented, women did not appear to benefit from CEA, and the overall positive result for surgery was only realized with a very low 2.3% perioperative stroke or death rate. These concerns, coupled with the fact that the natural history of asymptomatic carotid stenosis is fairly benign with an annual stroke or death risk on the order of only 1% to 2%,23 24 suggest that the results of ACAS may be statistically but not clinically significant. It may be argued that before the ACAS results were first published in December 1994,25 halfway during our study period, there was even less compelling scientific evidence to suggest that asymptomatic stenosis was a good indication for CEA. Because the benefit of CEA for asymptomatic stenosis seems marginal and dependent on both the patients treated and a very low operative complication rate, we decided a priori in our analysis that this indication would be considered "uncertain" rather than unequivocally "appropriate."
Data from randomized controlled trials have afforded an opportunity to base determinations of CEA appropriateness on objective evidence of surgical efficacy. Previous studies evaluating the appropriateness of CEA may have been limited by biases in the opinions of what was considered appropriate surgery.26 27 28 29 Our analysis is also unique in that it links surgical appropriateness with standardized carotid stenosis remeasurements. Our choice of the NASCET method of measurement was based on its relatively high intraobserver and interobserver reliability30 and its use in most of the randomized controlled CEA trials that have provided the basis of our classification of appropriateness.9 11 12 13 31 The finding of our study, where reasonable but not strong agreement was found between the original radiologist's interpretation and the remeasurement value, validates previous concerns that CEA may be performed on the basis of inaccurate or nonuniform stenosis measurements.32 However, the actual impact of this discrepancy on the management of our patients could not be determined, since it is not known whether each surgeon in our study based treatment on the radiologist's report or on personal review and measurement of the angiogram. The fact that the most common discrepancy found was an overestimation of stenosis severity suggests that surgeons either were not consistently and accurately remeasuring angiograms with the NASCET method before making a decision regarding surgery or were making management decisions only partly based on the degree of stenosis.
We found that the sensitivity of ultrasound for assessing angiographic
stenoses in our study population was fairly high, although the
specificity of this imaging technique was only moderate. As well, the
reliability of ultrasonography in our region may be suspect, since the
positive predictive value of ultrasonography was only 50% for
detecting severe stenoses
80%. In our series, carotid
ultrasound tended to overestimate the actual severity of carotid
stenosis. Other studies have shown ultrasonography to be less
accurate in assessing mild and moderate stenoses than severe
stenoses, with one study demonstrating test sensitivities
ranging from 25% to 92%, depending on the degree of vessel
narrowing.33 34 35
In our study, by combining the best indication for surgery as
ascertained from patient records with the carotid stenosis
remeasurement value, we found that 49% of patients who underwent CEA
had an uncertain indication and that the majority of these patients had
asymptomatic stenoses
60%. Inappropriate CEAs
were found in 18% of our patient population or in almost 1 in every 5
patients overall. This group was made up largely of patients with
<60% asymptomatic stenoses, of which 62% (23/37)
had original angiographic readings that overestimated the NASCET
remeasurement value. The remainder in this group underwent surgery in
the face of neurological instability or high-risk medical comorbidity.
An argument can be made, however, to consider neurologically unstable
patients separately rather than as inappropriate surgical candidates a
priori. Although unproven, it may be that some of these patients may in
fact benefit overall from CEA, even with an elevated attendant
perioperative complication rate, if their risk of
stroke or death without surgery is greater than with CEA.
While efficacy of CEA for symptomatic stenoses <70% may yet be shown in the continuing part of NASCET, perhaps the most disquieting finding in our analysis was the large proportion of patients undergoing surgery for asymptomatic stenosis. Available evidence suggests that any modest benefit from surgery for asymptomatic patients is realized only with a very low perioperative complication rate, which may be difficult to achieve outside the research setting.
Complications of CEA
A recent literature review of studies published since 1980 that
examined the results of CEA performed for symptomatic
carotid stenosis found a mean stroke or death rate of 5.6%
(95% CI, 4.4 to 6.9).36 For the symptomatic
subgroup of patients in our series, the 5.2% stroke or death rate was
similar to this and the 5.8% rate found in NASCET.9
However, the 5.1% postoperative stroke or death rate in our
asymptomatic patients was higher than the 3.4% rate found
in a review of asymptomatic series37 and
significantly more than the corresponding 1.2% rate found in ACAS
(Fisher's exact test, P=.01).13 The
comparatively greater complication rate for our
asymptomatic patients probably negated any overall benefit
from CEA for this patient subgroup in our region. This observed higher
frequency of complications is unexplained, but it possibly may be
related to technical performance or patient selection or may
simply be a realistic overall portrayal of CEA as it is practiced in a
community-wide setting. Higher complication rates in community-based
studies, compared with randomized controlled trials, are not
unexpected. In randomized controlled trials, artificial constraints
such as stringent inclusion and exclusion criteria, generally excellent
patient care, and close patient follow-up may result in better outcomes
than in routine clinical practice.
Several groups have described potential risk factors for surgical complications after CEA.8 38 39 40 41 In 1975, Sundt et al19 provided evidence that patients with certain cardiovascular and neurological risk factors were at highest risk for postoperative myocardial infarction and stroke. Some of these same risk factors have been confirmed statistically in a retrospective analysis of 1160 CEA patients.20 The authors of this latter study found seven predictors that can stratify candidates for CEA at higher risks of stroke and cardiac complications: age over 75 years, symptomatic (versus asymptomatic) stenosis, severe hypertension, CEA in preparation for coronary artery surgery, a history of angina, intraluminal thrombus apparent on angiography, and intracranial arterial stenosis. Our analysis of a smaller group of patients identified a history of angina, a history of CHF, and lack of antiplatelet agent use before surgery as preoperative independent variables associated with stroke or death.
Although risk factors for cardiac complications alone after CEA have been less commonly studied in the literature, patients undergoing CEA frequently harbor occult or symptomatic cardiac disease.42 43 44 45 46 47 48 49 Our present study identified age over 75 years and a history of CHF as independent preoperative variables predictive of cardiac complications after CEA. The detection of these risk factors may allow the preoperative identification of high-risk patients who may then be given more intensive perioperative monitoring or treatment.50
The findings of this study emphasize the usefulness of a regional analysis in uncovering local clinical concerns. We determined that CEA may be overused in our region because of the substantial number of operations for inappropriate and uncertain indications. In particular, the observed high number of complications suggests restricting the use of CEA for our asymptomatic patients. We are currently undertaking a local prospective quality-control program to address the issues identified in this study. However, it may be reasonable to assume that these concerns are not isolated to our own region only. Because estimates have placed the proportion of operations for asymptomatic carotid disease at 25% to 50% of all CEAs performed in the United States,51 our disturbing findings regarding the misuse of CEA and elevated complication rates may reflect similar problems in other communities. It deserves mention that surgical audits such as reported here are time-consuming and expensive endeavors, and they require the interpretive skills of individuals familiar with cerebrovascular disease. As additional information from randomized controlled trials becomes available,52 thus more fully defining the indications for CEA, appropriateness classifications can be revised, new audits undertaken, and previous audits reanalyzed.
In summary, the combined rate of uncertain and inappropriate surgeries was high at 67% in our healthcare region, with half of all patients undergoing CEA for uncertain indications. Inappropriate surgery was seen in about 1 in 5 patients in this analysis and was related mainly to overestimation of mild and moderate asymptomatic carotid stenoses, but it was also due to the use of CEA in the presence of significant neurological and medical instability in some instances. The uniform use of a standard method of angiographic measurement of carotid stenosis may reduce the rate of surgeries for uncertain and inappropriate indications. A substantial proportion of our study population was asymptomatic, and any benefit of surgery for these patients was overshadowed by a significant risk of postoperative stroke or death. The preoperative identification of high-risk patients through risk factor analysis may offer an opportunity to reduce complication rates. Independent local audits of surgical performance are recommended to identify areas of concern at a regional level.
| Selected Abbreviations and Acronyms |
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Received November 18, 1996; revision received February 25, 1997; accepted March 3, 1997.
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