Update of the Evidence
for the USPSTF
Tracy Wolff, MD, MPHa; Janelle Guirguis-Blake, MDb; Therese Miller, DrPH.a; Michael
Gillespie, MD, MPH;b and Russell Harris, MD, MPHd
This article was first published in the Annals of Internal Medicine. Select for copyright and source information.
Contents
Abstract
Introduction
Methods
Results
Discussion
References
Notes
Abstract
Background: Cerebrovascular disease is the third leading cause
of death in the United States. The proportion of all strokes attributable to
previously asymptomatic carotid stenosis is low. In 1996, the US. Preventive Services Task Force concluded that evidence was insufficient to recommend for or
against screening of asymptomatic persons for CAS by using physical examination
or carotid ultrasonography.
Purpose: To examine the evidence of benefits and harms of
screening asymptomatic patients with duplex ultrasonography and treatment with
carotid endarterectomy for carotid artery stenosis (CAS).
Data
Sources: MEDLINE® and Cochrane Library
(search dates January 1994 to April 2007), recent systematic reviews, reference
lists of retrieved articles, and suggestions from experts.
Study Selection:
English-language randomized, controlled trials (RCTs) of screening for CAS;
RCTs of carotid endarterectomy versus medical treatment; systematic reviews of
screening tests; and observational studies of harms from carotid endarterectomy
were selected to answer the following questions: Is there direct evidence that
screening with ultrasonography for asymptomatic CAS reduces strokes? What is
the accuracy of ultrasonography to detect CAS? Does intervention with carotid
endarterectomy reduce morbidity or mortality? Does screening or carotid
endarterectomy result in harm?
Data
Extraction: All studies were
reviewed, abstracted, and rated for quality by using predefined USPSTF
criteria.
Data
Synthesis: No RCTs of screening for
CAS have been done. According to systematic reviews, the sensitivity of ultrasonography
is approximately 94%, and the specificity is approximately 92%. Treatment of
CAS in selected patients by selected surgeons could lead to an approximately 5–percentage
point absolute reduction in strokes over 5 years. Thirty-day stroke and death
rates from carotid endarterectomy vary from 2.7% to 4.7% in RCTs; higher rates
have been reported in observational studies (up to 6.7%).
Limitations: Evidence is inadequate to stratify people into
categories of risk for clinically important CAS. The RCTs of carotid
endarterectomy versus medical treatment were conducted in selected populations
with selected surgeons.
Conclusion: The actual stroke reduction from screening
asymptomatic patients and treatment with carotid endarterectomy is unknown; the
benefit is limited by a low overall prevalence of treatable disease in the
general asymptomatic population and harms from treatment.
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Introduction
Cerebrovascular
disease is the third leading cause of death in the United States.1
Approximately 500 000 people in the United States each year experience a first
stroke.1 The mortality rate for cerebrovascular disease has declined by
nearly 70% since 1950.2 Much of the decrease is probably due to reduced
cigarette smoking and improved control of hypertension.
Carotid
artery stenosis (CAS) is pathologic atherosclerotic narrowing of the
extracranial carotid arteries. The contribution of CAS to overall stroke burden
is difficult to approximate. Eighty-eight percent of strokes are ischemic, and 20%
or fewer of these are due to large-artery stenosis.3-9 A subgroup of patients
have large-artery stenosis due to stenosis of the carotid bifurcation or
proximal carotid artery that is approachable by carotid endarterectomy; some of
these patients are asymptomatic.
A "clinically
important degree of CAS" is defined as the percentage of stenosis that
corresponds to a substantially increased risk for stroke. Because stroke risk
depends on more than the degree of carotid artery narrowing, it is difficult to
define categories of CAS that are associated with various risk levels of stroke
in asymptomatic people. Most studies of treatment for CAS consider stenosis of 50% or greater or 60% or greater to be clinically
important. The most important risk factor
is previous cerebrovascular disease. Other risk factors include hemodynamic
factors; atrial fibrillation; collateral circulation; patient age (>65 years);
male sex; comorbid conditions; and cardiovascular risk factors, such as
hypertension, cigarette smoking, clotting mechanisms, and plaque structure.10-16 The presence of the strongest reported risk
factors, smoking or heart disease, approximately doubles the risk for CAS.14,15 However, no single risk factor or clinically useful risk model
incorporating multiple factors clearly discriminates people who have clinically
important CAS from people who do not.
Several
population-based cohort and cross-sectional studies have examined the prevalence
of CAS. These prevalence estimates are based on a positive result on a
screening carotid ultrasonography. Estimates of the prevalence of CAS from
population-based studies range from 0.5% to 8%.5,10,17–19 On the basis of population-based
studies and the accuracy of ultrasonography, we estimate the actual prevalence
of clinically important CAS (60% to 99%) to be approximately 1% or less in the
general primary care population and about 1% in persons age 65 years or older.
A detailed discussion on the prevalence of CAS is available in a larger report
at www.ahrq.gov/clinic/uspstf/uspsacas.htm.20
Carotid
endarterectomy has been proposed as a strategy for reducing the burden of suffering
due to stroke, in addition to controlling such risk factors as tobacco use and
hypertension. Randomized, controlled trials (RCTs) have shown that carotid
endarterectomy effectively reduces stroke among people who have severe CAS and
have had a transient ischemic attack or "minor stroke." It is not clear,
however, whether screening asymptomatic people (those who have never had a transient
ischemic attack) to detect CAS and treatment with carotid endarterectomy are effective
in reducing stroke.
Before
carotid endarterectomy, cerebral angiography after ultrasonography may be used
to confirm CAS. A small percentage of patients will be harmed by the angiographic
procedure itself. In an RCT of carotid endarterectomy in asymptomatic patients,
1.2% of patients who had angiography had a nonfatal stroke. Prospective studies
of cerebral angiography have found rates of persistent neurologic complications
of 0.1% to 0.5%.21-23 Because of the increased risk for stroke, there is
disagreement on whether cerebral angiography should be used to confirm a
positive ultrasonography screening result. Current practice varies widely: Some
surgeons do other confirmatory tests, such as magnetic resonance angiography
(MRA) or computed tomographic angiography (CTA), whereas others request
angiography before carotid endarterectomy.
In
1996, the U.S. Preventive Services Task Force (USPSTF) concluded that evidence was
insufficient to recommend for or against screening of asymptomatic persons for
CAS by using physical examination or carotid ultrasonography.24 This
recommendation was based on new evidence at the time, including data from ACAS
(Asymptomatic Carotid Artery Study), an RCT involving 1662 persons with
asymptomatic stenosis greater than 60%. Results of ACAS suggested that the
overall benefit of treatment with carotid endarterectomy depends greatly on the
perioperative complications. At that time, information was limited about carotid
endarterectomy complications in the general population. Since the previous Task
Force review, the largest RCT of carotid endarterectomy versus medical treatment
for asymptomatic CAS, the ACST (Asymptomatic Carotid Surgery Trial), and
several large studies on actual harms of carotid endarterectomy have been
published.
This
review updates the 1996 USPSTF review of screening for CAS, focusing on duplex ultrasonography
as the screening test (with various confirmatory tests) and carotid
endarterectomy as the treatment for clinically important CAS. Medical
interventions and screening with carotid auscultation were not reviewed in this
report. The USPSTF has reviewed screening for several known risk factors of
carotid artery stenosis and stroke, including hyperlipidemia, hypertension,
aspirin prophylaxis, and smoking. The evidence reports and recommendations are
available at the Agency for Healthcare Research and Quality (AHRQ) Web site at www.preventiveservices.ahrq.gov.
Figure 1 shows the analytic framework for this review, which was developed by following
USPSTF methods.25 The USPSTF developed 4 key questions from the analytic
framework to guide its consideration of the benefits and harms of screening
with ultrasonography for CAS. The key questions were as follows.
Key question 1: Is there direct
evidence that screening adults with duplex ultrasonography for asymptomatic CAS
reduces fatal or nonfatal stroke?
Key question 2: What is the accuracy
and reliability of duplex ultrasonography to detect clinically important CAS?
Key question 3: For people with
asymptomatic CAS 60% to 99%, does intervention with carotid endarterectomy
reduce CAS-related morbidity or mortality?
Key question 4: Does screening or carotid
endarterectomy for asymptomatic CAS 60% to 99% result in harm?
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Methods
The USPSTF designated key questions 1, 2, and 3 as
subsidiary questions for which they requested nonsystematic reviews to assist
them in updating their recommendations. Key question 4 was the only key
question for which the USPSTF requested a systematic evidence review.
Data
Sources and Searches
We
searched MEDLINE® for English-language articles published between 1 January 1994 and 2 April 2007 that addressed key questions 1, 2, and 3. We identified
additional studies by examining the reference lists of major review articles
and by consulting experts. For key question 3, we performed a MEDLINE® search
for RCTs, systematic reviews, and meta-analyses that compared carotid
endarterectomy with medical therapy for asymptomatic people with CAS. We
identified 1 in-process RCT by its inclusion in a systematic review, and we included
it once it was published.
For
key question 4, we performed a systematic search of MEDLINE® for English-language
articles published between 1 January 1994 and 2 April 2007 by using the focused Medical Subject Heading terms endarterectomy, carotid and outcome
and process assessment. We also selected a key study from this search and
identified related articles through MEDLINE®. Additional studies were identified
through a search of the Cochrane database, discussions with experts, and
hand-searching of reference lists from major review articles and studies.
Study
Selection
Titles
and abstracts of articles retrieved for key questions 1, 2, and 3 were nonsystematically
selected and reviewed by 2 reviewers. The process was considered nonsystematic
because articles were selected for review and abstracted by 1 reviewer.
Articles for key question 1 were selected for inclusion if they were RCTs; compared
screened versus nonscreened groups; used ultrasonography, MRA, or CTA as
screening methods; reported outcomes of strokes or death in asymptomatic persons;
and were performed in a population generalizable to the United States. For key
question 2, we included systematic reviews that compared screening tests (ultrasonography,
MRA, or CTA) with angiography in asymptomatic persons and were performed in a
population generalizable to the United States. Articles for key question 3 were
included if they were RCTs of carotid endarterectomy comparing surgical
treatment with medical treatment, reported 30-day complication rates (stroke
and death) of carotid endarterectomy, included only asymptomatic patients, and
were performed in a population generalizable to the United States.
For
key question 4, 3 reviewers independently reviewed the abstracts and selected
articles from titles and abstracts on the basis of inclusion and exclusion
criteria. In general, studies were selected if they were large, multi-institution,
prospective studies that reported 30-day mortality or stroke outcomes for
asymptomatic patients undergoing carotid endarterectomy. Studies were excluded
if they did not report outcomes by symptom status, included patients receiving carotid
endarterectomy combined with other major surgeries, were not performed in the United States, included patients with re-stenosis, or covered patients at extremely high
risk. Appendix Table 1 shows detailed search terms and inclusion and exclusion
criteria. Abstracts that were chosen by fewer than 3 reviewers were discussed
and selected on the basis of consensus.
Data
Extraction and Quality Assessment
For
all citations that met the eligibility criteria, 2 authors reviewed the full
articles and independently rated their quality. The 2 reviewers achieved consensus
about article inclusion, content, and quality through discussion; disagreements
were resolved by the involvement of a third reviewer. Data on the following
items were extracted from the included studies for key question 4: source
population; sample size; average age; proportion white; proportion male;
average degree of stenosis; and the proportion of persons with important comorbid
conditions, including contralateral stenosis, smoking, diabetes, hypertension,
and coronary artery disease. Quality evaluations of articles for all key questions
were performed by using standard USPSTF methods for determining internal and
external validity.25 We evaluated the quality of RCTs and cohort studies on
the following items: initial assembly of comparable groups, maintenance of
comparable groups, important differential loss to follow-up or overall high
loss to follow-up, measurements (equality, reliability, and validity of outcome
measurements), clear definition of the interventions, and appropriateness of
outcomes. We evaluated systematic reviews and meta-analyses on the following
items: comprehensiveness of sources considered, search strategy, standard
appraisal of included studies, validity of conclusions, recency, and relevance. Appendix Table 2 describes the criteria and definitions for USPSTF
quality ratings more thoroughly.
Data
Synthesis and Analysis
Because
the review was nonsystematic, we synthesized data from the included studies for
key questions 1, 2, and 3 qualitatively in tabular and narrative format. Although
we performed a systematic review for key question 4, we synthesized the data qualitatively
rather than quantitatively because of the different patient characteristics and
varied outcome assessments. Synthesized evidence was organized by key question.
Role
of the Funding Source
The
general work of the USPSTF is supported by the Agency for Healthcare Research
and Quality. This specific review did not receive separate funding.
Return to Contents
Results
In
summary, we found no direct evidence of the benefit of screening with ultrasonography
for CAS in asymptomatic adults (key question 1). We found 2 systematic reviews
on the accuracy of ultrasonography screening (key question 2); for CAS 60% to 99%,
the sensitivity is approximately 94% and the specificity is approximately 92%.
Three fair- or good-quality RCTs were found and reported that in selected
patients with selected surgeons, treatment with carotid endarterectomy for
asymptomatic CAS could lead to an approximately 5—percentage point absolute
reduction in strokes over 5 years (key question 3).
For
key question 4, the initial literature search for the systematic review returned
397 titles. The titles, abstracts, and full articles were reviewed by 3 reviewers,
who excluded 232 studies after review of returned titles. Most of the studies
were excluded at the title stage because they were not on carotid
endarterectomy, were not multisite, or only included outcomes for symptomatic persons.
The reviewers excluded 134 studies at the abstract stage (Figure 2). Most
studies were excluded because they included only symptomatic persons, were not multisite,
had no relevant outcomes, or had a small sample. Three full articles were
identified through expert consultation or from reviewing the reference lists of
major review articles. Twenty full articles were excluded because they were an incorrect
type, were not multisite, only included symptomatic persons, or did not report
relevant outcomes. Fourteen articles were ultimately included for key question
4 on the harms of carotid endarterectomy. In addition, 3 good- or fair-quality
RCTs identified for key question 3 provided evidence on harms under trial
conditions.
The
harms of carotid endarterectomy for asymptomatic CAS, reported in most studies
as 30-day stroke and death rates, vary from 2.7% to 4.7% in the RCTs; higher
rates have been reported in observational studies (up to 6.7%). The results of
the literature search and synthesis are discussed below, under the
corresponding key question subheading.
Key
Question 1
Is
there direct evidence that screening adults with duplex ultrasonography for
asymptomatic CAS reduces fatal or nonfatal stroke?
We
found no studies addressing this question that met our inclusion criteria.
Key
Question 2
What
is the accuracy and reliability of ultrasonography to detect clinically
important CAS?
We
found 2 meta-analyses on the accuracy of ultrasonography to detect clinically
important stenosis. A recent meta-analysis by Nederkoorn and colleagues
included studies published from 1993 through 2001 and estimated the accuracy of
carotid duplex ultrasonography using digital subtraction angiography as the
reference standard; this meta-analysis was rated as fair quality because it had
limited sources for studies and did not have information on the standard
appraisal of studies.26 Carotid duplex ultrasonography had an estimated
sensitivity of 86% (95% CI, 84% to 89%) and a specificity of 87% (CI, 84% to 90%)
for detecting CAS of 70% to 99%.26 A second meta-analysis of carotid duplex ultrasonography
found similar sensitivity and specificity for carotid duplex ultrasonography to
detect 70% or greater stenosis (90% [CI, 84% to 94%] and 94% [CI, 88% to 97%], respectively).27 This meta-analysis was rated good quality because of the
comprehensiveness of sources and search strategies, the explicit selection
criteria, and the standard appraisal of studies. To detect CAS 50% or greater,
the authors suggested a cut-point that had a sensitivity of 98% and a
specificity of 88%. By using a graph in that article and applying the same cut-point
as was suggested for detecting CAS 70% or greater, we estimate that the
sensitivity of carotid duplex ultrasonography to detect CAS 60% or greater is
about 94%, with a specificity of about 92%.
The
reliability of carotid duplex ultrasonography is questionable. One
meta-analysis noted that the measurement properties used among various ultrasonography
laboratories varied greatly, to a clinically important degree.27
We
found 1 meta-analysis on the accuracy of MRA and 1 meta-analysis on the
accuracy of CT in detecting clinically important carotid stenosis. The fair-quality
meta-analysis by Nederkoorn and colleagues reported that MRA has about the same
accuracy as ultrasonography.26 CTA has gained wide acceptance in some
centers as a follow-up test to ultrasonography in confirming CAS. In certain
cases, it has been used in place of vascular arteriography. A recent good-quality
systematic review that used comprehensive data sources and a standard appraisal
of studies found that the accuracy of CTA does not greatly differ from that of ultrasonography
and MRA28 Although CTA is safer than angiography as a confirmatory test, it
is unlikely to be a useful screening test because of its cost and because it
entails radiation exposure and injection of intravenous contrast dye. Although MRA
does not use contrast dye or have significant radiation exposure, it is time-consuming
and costly and is also not suitable as a screening test at this time.
Key Question 3
For people with asymptomatic CAS 60% to 99%, does
intervention with carotid endarterectomy reduce CAS-related morbidity or
mortality?
We
identified 5 RCTs comparing carotid endarterectomy and medical management for
asymptomatic CAS: the WRAMC (Walter Reed Army Medical Center) study,29 the MACE
(Mayo Asymptomatic Carotid Endarterectomy) study,30 the VACS (Veterans
Affairs Cooperative Study,31 ACAS,32 and ACST.33 We selected for
inclusion 2 good-quality studies (ACAS and ACST) and 1 fair-quality study
(VACS). We excluded the WRAMC study because it did not use ultrasonographic
assessment of CAS, had few participants, and used unclear definitions of
outcomes. We excluded the MACE study because of its small number of
participants, small number of strokes, and lack of aspirin treatment in the
surgical group.
Study
Characteristics
The
3 fair- or good-quality studies, VACS, ACAS, and ACST, compared carotid
endarterectomy plus medical management with medical management alone in persons
without symptoms attributable to the studied artery. Table 1 shows characteristics
and outcomes of these studies, and Appendix Table 3 provides more detail
on all RCTs. Medical management included the standard risk factor management at
the time of the trials, including aspirin and some degree of blood pressure and
lipid control. In VACS, 444 men with 50% to 99% stenosis confirmed by
angiography were randomly allocated and followed for a mean of 47.9 months.34
All participants were male, 88% were white, and the median age was 64.5 years.
The participants had a generally high cardiovascular risk: Approximately 50%
were current cigarette smokers, about 30% had diabetes, and 63% had
hypertension.
The
ACAS screened about 42 000 people and selected 1662 with angiographically
confirmed CAS 60% or greater for random allocation to carotid endarterectomy or
medical therapy.32 The sample was 95% white and 66% male, and the mean age
of participants was 67 years. The participants had high cardiovascular risk: About
20% had had a previous contralateral carotid endarterectomy, more than 20% had
had a previous contralateral transient ischemic attack or stroke, 64% had
hypertension, 26% smoked cigarettes, and 23% had diabetes. Surgeons with low carotid
endarterectomy complication rates were selected for participation in the study.
The
international, multicenter ACST randomly assigned 3120 persons with CAS 60% or
greater and followed them for a mean of 3.4 years.33 Both groups received
medical management by their primary care providers. Although it is difficult to
determine the intensity of medical management, the mean systolic blood pressure
at baseline for all participants was 153 mm Hg and mean total cholesterol level
was 5.8 mmol/L [224 mg/dL]. Aspirin was widely used. More than 50% of the
patients were receiving antihypertensive medications, but the achieved systolic
blood pressure was not reported. Lipid-lowering agents were used less frequently
at the beginning of the study and were used by more than 50% of participants
during the last 3 years of the study. The degree of CAS was determined by ultrasonography.
Angiography was not required but was often used for confirmation of CAS during
the first few years of the study, and less frequently used in the final years.
As in ACAS, patients were carefully selected and were generally at high
cardiovascular risk, and surgeons were carefully selected for low complication
rates. The mean age was 68 years, and 66% of participants were male, 65% had
hypertension, 20% had diabetes, and 24% had had a previous contralateral carotid
endarterectomy.
Summary
of Study Results
The
2 largest and highest-quality RCTs have shown an absolute reduction of stroke
and perioperative death of approximately 5% from carotid endarterectomy compared
with medical treatment for CAS 60% to 99% in selected patients with selected
surgeons. This benefit includes an approximate 3% rate of perioperative stroke
or death.
After
4 years of follow-up, the stroke rate in VACS was lower in the carotid
endarterectomy group than in the medical treatment group (8.6% vs. 12.4%).
However, the incidence of perioperative stroke or death in the carotid
endarterectomy group was 4.7%. When all strokes or perioperative events were
considered, there was no difference between carotid endarterectomy and medical
management. After 2.7 years of follow-up, the ACAS investigators calculated 5-year
outcomes on the basis of Kaplan–Meier curves. They estimated that the 5-year
rate of ipsilateral stroke and any perioperative stroke or death was lower in
the carotid endarterectomy group than in the medical therapy group (5.1% vs. 11.0%;
relative risk reduction [RRR], 0.53 [CI, 0.22 to 0.72]) If strokes associated
with angiography were included, the difference between groups was 5.6% versus
11.0%, or an absolute difference of 5.4 percentage points over 5 years. These
rates include a perioperative rate of stroke or death of 2.7% overall (1.7% for
men and 3.6% for women). The estimated RRR was greater for men than for women:
0.66 and 0.17, respectively. The treatment groups did not statistically
significantly differ in all-cause mortality. After 3.4 years of follow-up, the
ACST investigators calculated 5-year outcomes. They estimated that the carotid
endarterectomy group would have a lower 5-year rate of any stroke or
perioperative death than the medical group: 6.4% versus 11.8% (difference, 5.4
percentage points [CI, 2.96% to 7.75% percentage points]). About half of the
strokes prevented by carotid endarterectomy were disabling. The perioperative
rate of stroke or death was 3.1% overall and was higher for women than for men
(3.7% vs. 2.4%). The groups did not statistically significantly differ in
all-cause mortality.
The
RCTs on carotid endarterectomy for asymptomatic CAS have important limitations.
The participants and surgeons in the RCTs were highly selected, which reduces
the generalizability of the findings to the primary care setting. In addition,
the 30-day perioperative results of the RCTs were reported as a combined
outcome and did not include an important complication, acute nonfatal
myocardial infarction. Another important limitation of the RCTs on treatment
with carotid endarterectomy is that the medical treatment arm in the RCTs was poorly
defined, was not kept constant over the course of the study, and was probably not
comparable to current standards of optimal medical management.
Key
Question 4
Does
screening or treatment for asymptomatic CAS 60% to 99% with carotid
endarterectomy result in harm?
The
potential harms of a program of screening for CAS for the purpose of performing
carotid endarterectomy include the harms associated with false-positive
screening tests (for example, anxiety; labeling; the harms of any confirmatory
work-up, such as angiography; or the harms of unnecessary carotid
endarterectomy in people who do not undergo angiography); and the harms of carotid
endarterectomy itself (for example, bleeding, infection, stroke, and death).
The harms of angiography are discussed in the introduction to this article. We
found no studies on anxiety or labeling among people with false-positive results
on ultrasonography screening. We did find evidence concerning the harms of carotid
endarterectomy. Carotid endarterectomy entails a clear risk for perioperative
complications of carotid endarterectomy, including stroke, death, and
myocardial infarction. Some observational studies have shown rates of
perioperative complications that were higher than the 3% reported in the RCTs.
Study
Characteristics
We
identified 14 good- or fair-quality studies that met our inclusion criteria and
evaluated carotid endarterectomy complications in patients with asymptomatic
CAS. Appendix Table 4 shows detailed study characteristics, quality
ratings, and results of the observational studies. Thirteen observational
studies were secondary analyses of administrative databases: 2 studies used
data on patients attending a Veterans Affairs medical center,.35-36 7 studies
used data from patients receiving Medicare benefits,.37-43 and 4 studies
used a similar data set of patients admitted to 6 New York hospitals.44-47
The final study was a systematic review of studies published between 1994 and
2000 on harms of carotid endarterectomy.48 The primary perioperative
complication measure in the studies was either death/stroke or
death/stroke/myocardial infarction within 30 days of surgery. All of the
observational studies included patients referred to a hospital or medical
center for carotid endarterectomy as a result of CAS. Few data were provided on
the severity of stenosis. The studies included patients who did and did not have
neurologic symptoms, but we reviewed only studies that reported complication
rates separately for asymptomatic patients. The mean age of patients ranged
from 67 to 74 years. Six of the studies collected information on race; in those
studies, most participants were white (range, 87% to 95%). Almost all
participants in the 2 Veterans Affairs studies were male, whereas the other
studies include 36% to 47% women.
Bratzler
and colleagues used a claims database and medical records from Medicare
recipients who underwent carotid endarterectomy in 1993 or 1994.37 We
quality rated this study as good: Data for outcomes were collected from 2 sources,
correlation between data abstractors was high, and the investigators used
standard definitions of outcomes. The fair-quality study by Cebul and
colleagues used Ohio Medicare claims data on patients who underwent carotid
endarterectomy between July 1993 and June 1994; their sample was predominantly
white, and the study used only a subset of all patients receiving carotid
endarterectomy during the time frame.38
Two
good-quality studies on the same database of patients undergoing carotid
endarterectomy at Veterans Affairs medical centers had well-defined inclusion
criteria and abstraction processes and used methods that probably limited
differential outcome measurement, including contacting all patients and
families 30 days after surgery35-36 Two good-quality studies by Kresowik
and colleagues used Medicare claims databases from 10 states; the first was
conducted for June 1995 to May 1996, and the second for June 1998 to May 1999.41-42 These studies were very large and included medical record data in addition
to data in the claims database. Another good-quality study by Kresowik and
colleagues used similar methods as above but used the Iowa Medicare database.43
A fair-quality study by Karp and colleagues used Medicare claims data from Georgia; agreement between the reviewer and the physicians on indications for surgery was
limited.40
Four
studies used the same database of Medicare recipients from 6 New York hospitals
who had carotid endarterectomy in 1997 or 1998.44-47 The individual
studies used similar methods but had different research questions and
consequently excluded cases with missing data using different criteria. Although
these 4 studies had some limitations, the overall quality of the studies was
rated as good because both outpatient and inpatient data were used for outcome
measurement, studies used trained independent abstractors, 2 investigators
independently reviewed records of patients with an outcome, and few patients
were excluded because of missing data.
The
2007 study by Halm and colleagues was performed on an administrative database
of Medicare recipients in New York State who received carotid endarterectomy
between January 1998 and June 1999.39 We rated this study as fair-quality owing
to several limitations, including the exclusion of many patients because of
missing data. The systematic review by Bond and colleagues included studies
that reported 30 day stroke and death rates by indication and excluded studies
on combined carotid endarterectomy and coronary artery bypass grafting.48
This study had several limitations, including a lack of discussion on the
standard assessment of study quality, that resulted in a fair-quality rating.
Summary
of Study Results
The
30-day perioperative stroke or death rates in asymptomatic persons in the
Medicare and New York City studies ranged from 2.3% to 3.7%. One Veterans
Affairs study showed a perioperative stroke or death rate of 1.6%.35 The
systematic review of 103 studies found an overall stroke and death rate at 30
days of 3.0% in studies published since 1995.48
The
observational studies that reported on perioperative nonfatal myocardial
infarction showed a rate of approximately 0.7% to 1.1%,35,40,44 Patients
with more comorbid conditions had a rate of nonfatal myocardial infarction up
to 3.3%.44 The rate of nonfatal perioperative myocardial infarction reported
for the surgical group in the RCTs varied from 1.9% in VACS to 0.6% in ACST.31,33 The participants did not receive routine postoperative electrocardiography
or serum markers of myocardial involvement.
Two
Medicare-based studies found variation in perioperative stroke and death among
10 states.41,42 In the first study, the statewide rates ranged from 2.3% in
Indiana to 6.7% in Arkansas.41 A follow-up study for the same 10 states
found similar results as in 2001, with rates ranging from 1.4% in Georgia to 6.0% in Oklahoma.42
Studies
provided little information about rates of other complications, including the
impact on quality of life. None of the observational studies that we evaluated
gave specific rates of other complications for asymptomatic patients. However,
among the RCTs, the VACS reported a surgical complications rate of 3.8% for
cranial nerve injuries (none of these injuries were permanent), 5.2% for
hypotension, and 25% for hypertension.34
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