nlmpubs.nlm.nih.gov/2014.05.nlmpubs.nlm.nih.gov.tar/nlmpubs.nlm.nih.gov/alerts/carotid.txt

Text File | 1994-10-02 | 8KB | 141 lines

CLINICAL ADVISORY:  Carotid Endarterectomy for Patients With
Asymptomatic Internal Carotid Artery Stenosis
    SUMMARY: The investigators of the Asymptomatic Carotid
Atherosclerosis Study (ACAS) are reporting the interim results
of a randomized controlled clinical trial of carotid
endarterectomy in patients who have asymptomatic carotid
stenosis of greater than 60  percent reduction in diameter. In
addition to aspirin and aggressive management of modifiable risk
factors, one-half of the patients were randomly assigned to
receive surgery after angiographic confirmation of the lesion.
Carotid endarterectomy is beneficial with a statistically
significant absolute reduction of 5.8 percent in the risk of the
primary end point of stroke within 5 years and a relative risk
reduction of 55 percent. As a consequence of the trial reaching
statistical significance in favor of endarterectomy, and on the
recommendation of the study's data monitoring committee,
physicians participating in the study were immediately notified
and advised to reevaluate patients who did not receive surgery.
It is important to note that the success of the operation is
dependent on medical centers and surgeons who have a documented
perioperative morbidity and mortality of less than 3 percent,
careful selection of patients, and postoperative management of
modifiable risk factors.
    OBJECTIVE: The primary question of efficacy addressed by the
ACAS trial was: Among patients with severe but asymptomatic
carotid artery stenosis, does carotid endarterectomy, despite a
perioperative risk of any stroke or death from any cause, reduce
the overall 5-year risk of fatal and non-fatal ipsilateral
carotid stroke?(1)
    STUDY SITES: The trial was conducted in 39 U.S. and Canadian
centers that had been rigorously evaluated for neurological
expertise, quality of the ultrasound laboratory assessment, and
the quality of surgical management.(2,3) The participating
surgeons had met stringent criteria demonstrating a
perioperative complication rate less than 3 percent when the
indication for operation was asymptomatic carotid
stenosis.
    PATIENT ELIGIBILITY: Patients were eligible for
randomization if they were 40-79 years of age, had a life
expectancy of at least 5 years, gave informed consent and had at
least 60 percent carotid stenosis near the bifurcation of the
common or internal carotid artery measured in one of the
following three ways:
    A. Conventional or arterial digital subtraction angiography
indicating diameter stenosis of at least 60% using minimal
residual lumen (MRL) and the distal lumen (DL) in the equation
[1-(MRL/DL)] x 100.
    B. Doppler ultrasonography showing a peak systolic frequency
or end diastolic frequency greater than the machine-specific
cutpoint with predicted false positive rate of 5% determined by
correlation of Doppler flow velocities with arteriography in 50
consecutive cases.
    C. Doppler ultrasonography showing a peak
systolic frequency or end diastolic frequency greater than the
machine-specific cutpoint with predicted 10% false positive and
OPG-Gee examination pressure reduction of > 5 mm Hg.
    Patients were excluded for conditions which were likely to
cause mortality or render follow-up difficult within the 5-year
period. No patients with symptoms associated with TIA/stroke or
previous endarterectomy on the randomized artery were included.
Other exclusions were unstable angina pectoris, uncontrolled
atrial fibrillation, severe diabetes, uncontrolled hypertension,
renal insufficiency, hepatic disease, cancer, and other
conditions which would confound evaluation for end points or
contraindicate surgical management.
    INTERVENTION: After obtaining informed consent, one-half of
the patients were randomly allocated to surgical management.
Patients randomized to surgical management who did not have a
prerandomization arteriogram, had an arteriogram prior to
surgery to verify the degree of stenosis and to ascertain
whether there were contraindications to endarterectomy, such as
distal arterial disease. All patients were started on 325mg of
aspirin daily and aggressive reduction of modifiable risk
factors.
    MAIN OUTCOME MEASURES: The primary end point for evaluation
was any stroke or death following randomization and within the
30 day perioperative period for patients receiving surgery, a
comparable 42 day period from randomization for those not
assigned to surgery, and any ipsilateral stroke or stroke death
thereafter. All neurological symptoms and/or signs were
evaluated by a neurologist. Patients were interviewed about
neurologic symptoms and medical status every 3 months,
alternating between telephone and in-clinic interviews. During
the clinic visit, a neurologist examined the patient and the
ACAS surgeon or his designee made a second assessment if
symptoms or signs were found. All potential end points were
adjudicated by a blinded end point review committee.
    MAIN RESULTS: Between December 1987 and December 1993, 1662
eligible patients were randomized, 828 to receive surgery and
834 to medical management only. Analysis of randomized patients
shows a male to female preponderance of 2:1; approximately half
were between the ages of 60 and 69 and 37 percent were 70 or
older. Ninety-five percent were Caucasian. Recognized risk
factors for stroke, such as hypertension (64%), diabetes (23%),
prior myocardial infarction (21%), prior contralateral
TIA/stroke (25%) and smoking (26%), were balanced between the
two groups.
    As of July 31, 1994, the median follow-up was 2.7 years and
there were 4,465 patient years of observation for endpoints. The
aggregate risk of any stroke or death in the perioperative
period for the surgery group was 2.3%. Of 424 post-randomization
arteriograms, 31 were Doppler false positive (7.4%) and five
strokes were precipitated by arteriography (1.2%). Utilizing
Kaplan-Meier projections in an intention-to-treat analysis, the
aggregate risk over 5 years for the primary outcome was 4.8% for
patients who were assigned to receive surgery and 10.6% for
patients who were treated medically. The relative risk reduction
conferred by surgery was 55 percent (23-73%, 95 percent
confidence interval, p=0.004).
    Following endarterectomy, men had 69 percent relative risk
reduction of primary endpoint, while women had a 16 percent
relative risk reduction. Additional analyses and study will be
required to explore the reasons for this apparent difference.
The ACAS trial group is now completing follow-up, expanding the
database, performing additional statistical analyses, and
seeking expeditious publication of results.
    CONCLUSION: Carotid endarterectomy, performed in medical
centers with documented combined perioperative morbidity and
mortality for asymptomatic endarterectomy of less than 3
percent, and on carefully selected patients who continue to
have aggressive modifiable risk factor management is beneficial
for patients who meet eligibility criteria of asymptomatic
carotid stenosis exceeding 60 percent diameter reduction
confirmed by arteriography.
    References
    1. The Asymptomatic Carotid Atherosclerosis Study Group
(Toole JF, Howard, VJ, Chambless LE): Study design for
randomized prospective trial of carotid endarterectomy for
asymptomatic atherosclerosis. Stroke 1989;20:844-849.
    2. Howard G, Chambless LE, Baker WH, Ricotta JJ, Jones AM,
O'Leary D, Howard VJ, Elliott TJ, Lefkowitz DS, Toole JF: A
multicenter validation study of Doppler ultrasound versus
angiogram. J Stroke Cerebrovasc Dis 1991;1:166-173.
    3. Moore WS, Vescera CL, Robertson JT, Baker H, Howard VJ,
Toole JF:  Selection process for participating surgeons in the
Asymptomatic Carotid Atherosclerosis Study (ACAS). Stroke
1991;22:1353-1357.
    Keywords: Carotid stenosis, endarterectomy, stroke,
randomized trial, carotid ultrasonography