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Clinical Alert: Clinical Advisory on Carotid Endarterectomy for Patients With Asymptomatic Internal_carotid_artery Stenosis Clinical Alert: Clinical Advisory on Carotid Endarterectomy for Patients With Asymptomatic Internal_carotid_artery Stenosis National Institutes of Neurological_disorders and Stroke (NINDS) September 28,1994 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_assigned randomly 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_notified immediately 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_documented a 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 nonfatal ipsilateral carotid stroke?( 1) STUDY SITES: The trial was_conducted in 39 U_s . and Canadian centers that had_been_evaluated rigorously 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_uncontrolled unstable angina_pectoris 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_allocated randomly 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_recognized Caucasian 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 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. 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. 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 The full text of this alert has_been_mailed to all libraries that are members of the National Network of Libraries of Medicine. U_s. National Library of Medicine, 8600 Rockville Pike, Bethesda, MD 20894 National_institutes_of_health, Department_of_health & Human Services Copyright, Privacy, Accessibility Last updated: 15 March 1996