JStroke Cerebrovasc Dis 1995;5:56-57 © 1995 National Stroke Association
National Institute of Neurological Disorders and Stroke Clinical Advisory
Carotid Endarterectomy for Patients with Asymptomatic Internal Carotid Artery Stenosis
The investigators of the Asymptomatic Carotid Atherosclerosis Study 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% 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 angiograhic confirmation of the lesion. Carotid endarterectomy is beneficial with a statistically significant absolute reduction of 5.8% in the risk of the primary end point of stroke within 5 years and a relative risk reduction of55%. 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 th e operation depends on medical centers and surgeons who have a documented perioperative morbidity and mortality of less than 3%, careful selection of patients, and postoperative management of modifiable risk factors . Key Words: Carotid stenosis-Endarterectomy-Stroke-Randomized trial-Carotid ultrasonography.
Objective The primary question of efficacy addressed by the Asymptomatic Carotid Atherosclerosis Study (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 overallS-year risk of fatal and nonfatal ipsilateral carotid stroke (I)?
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% when the indication for surgery was asymptomatic carotid stenosis. 56 ] STROKE CEREBROVASC DIS, VOL. 5, NO.1, 1995
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% carotid stenosis near the bifurcation of the common or internal carotid artery measured in one of the following three ways . 1. 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 - (MRLlDL] X 100. 2. 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. 3. Doppler ultrasonography showing a peak systolic frequency or end-diastolic frequency greater than the machine-specific cutpoint with predicted
CAROTID ENDARTERECTOMY IN ASYMPTOMATIC ICA STENOSIS
10% false-positive and OPG-Gee examination pressure reduction of >5 mm Hg. Patients were excluded for condtions that were likely to cause mortality or render follow-up difficult within the 5-year period. No patients with symptoms associated with transient ischemic attack/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 that 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 325 mg of aspirin daily and aggressive reduction of modifiable risk factors.
ty-five percent were Caucasian. Recognized risk factors for stroke, such as hypertension (64%), diabetes (23%), prior myocardial infarction (21%), prior contralateral transient ischemic attack/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 end points. The aggregate risk of any stroke or death in the perioperative period for the surgery group was 2.3%. Of 424 postrandomization 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% (23-73%, 95% confidence interval, p = 0.004). Following endarterectomy, men had 69% relative risk reduction of primary end point, whereas women had a 16% 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 data base, performing additional statistical analyses, and seeking expeditious publication of results.
Main Outcome Measures The primary end point for evaluation was any stroke or death following randomization and within the 3D-dayperioperative 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 neurological 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, 1,662 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% were 70 or older. Nine-
Conclusions Carotid endarterectomy, performed in medical centers with documented combined perioperative morbidity and mortality for asymptomatic endarterectomy of less than 3%, 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% 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;20:844-9. 2. Howard G, Chambless LE, Baker WH, et aI. A multicenter validation study of Doppler ultrasound versus angiogram. J Stroke Cerebrovasc Dis 1991;1:166-73. 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;22:1353-7.
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