Endarterectomy for Asymptomatic Carotid Artery Stenosis Executive Committee for the Asymptomatic Carotid Atherosclerosis Study

Objective.\p=m-\To determine whether the addition of carotid endarterectomy to tion in individuals with asymptomatic he- aggressive medical management can reduce the incidence of cerebral infarction in modynamically significant carotid artery patients with asymptomatic carotid artery stenosis. stenosis? Design.\p=m-\Prospective, randomized, multicenter trial. Setting.\p=m-\Thirty-nineclinical sites across the United States and Canada. For editorial comment see 1459. Patients.\p=m-\Between December 1987 and December 1993, a total of 1662 pa- tients with asymptomatic carotid artery stenosis of 60% or greater reduction in di- Secondary objectives were to deter¬ ameter were data are available on 1659. At rec- randomized; follow-up baseline, mine the surgical success in lesion re¬ were ognized risk factors for stroke similar between the two treatment groups. moval and the incidence ofrecurrent ca¬ Intervention.\p=m-\Dailyaspirin administration and medical risk factor management rotid stenosis, the rate of progression or for all patients; carotid endarterectomy for patients randomized to receive surgery. regression of carotid atherosclerosis in Main Outcome Measures.\p=m-\Initially,transient ischemic attack or cerebral infarc- the medically treated comparison group, tion occurring in the distribution ofthestudy artery and any transient ischemic attack, and the incidence of all other vascular stroke, or death occurring in the In March 1993, the events, such as TIA, myocardial infarc¬ perioperative period. primary vascular outcome measures were changed to cerebral infarction occurring in the distribution tion, and death related to dis¬ of the study artery or any stroke or death occurring in the perioperative period. ease during follow-up. Results.\p=m-\Aftera median follow-up of 2.7 years, with 4657 patient-years of ob- METHODS servation, the risk over 5 for stroke and aggregate years ipsilateral any periopera- The design and of the tive stroke or death was estimated to be 5.1% 11.0% organization for surgical patients and for ACAS are detailed elsewhere.13 treated Thirty- patients medically (aggregate risk reduction of 53% [95% confidence inter- nine clinical centers were chosen from an val, 22% to 72%]). applicant pool of 55. All obtained institu¬ Conclusion.\p=m-\Patientswith asymptomatic carotid artery stenosis of 60% or tional review board approval ofthe study greater reduction in diameter and whose general health makes them good candi- protocol. dates for elective surgery will have a reduced 5-year risk of ipsilateral stroke if ca- rotid endarterectomy performed with less than 3% perioperative morbidity and Recruitment mortality is added to aggressive management of modifiable risk factors. Study participants were recruited from (JAMA. 1995;273:1421-1428) ultrasound vascular laboratories, practi¬ tioners who auscultated carotid bruits, and physicians who found carotid steno¬ MORE THAN 500 000 new strokes occur abling stroke may occur in 20% of pa¬ sis during evaluation for peripheral vas¬ annually in the United States, and it has tients, and thereafter in 1.5% to 5% an¬ cular surgery or contralateral CEA. been estimated that carotid artery dis¬ nually.6"8 On the other hand, the 30-day Inclusion criteria were age between ease may be responsible for 20% to 30% major morbidity and mortality for pa¬ 40 and 79 years; compatible history and of them.1 The annual stroke event rate tients who undergo surgery for asymp¬ findings on physical and neurological for asymptomatic patients with hemody- tomatic stenosis ranges from 0.0% to 3.8%, examinations; performance of required namically significant carotid artery ste¬ and that for patients with symptomatic laboratory and electrocardiograph^ ex¬ nosis ranges from 2% to 5%.2"6 Carotid stenosis may be 6%.9 Because the role of aminations no earlier than 3 months be¬ artery stenosis usually is identified after carotid endarterectomy (CEA) for asymp¬ fore randomization; patient accessibil¬ transient ischemie attack (TIA), but for tomatic carotid artery stenosis had not ity and willingness to be followed for 5 many patients, cerebral infarction caused been proved,10-12 the Asymptomatic Ca¬ years; and valid informed consent. by artery-to-artery embolism or carotid rotid Atherosclerosis Study (ACAS) was Exclusion criteria were cerebrovascu¬ occlusion is the initial event. Progression initiated in 1987.13 The ACAS is an in¬ lar events in the distribution of the study of asymptomatic carotid artery stenosis vestigator-initiated randomized trial de¬ carotid artery or in that of the vertebro- to occlusion is unpredictable and can be signed to test whether CEA should be a basilar arterial system; symptoms refer¬ disastrous; at the time of occlusion, dis- component of management for selected able to the contralateral cerebral hemi¬ patients with asymptomatic stenosis of sphere within the previous 45 days; the common carotid the internal ca¬ contraindication to a A complete list of the collaborators in the bulb, aspirin therapy; dis¬ Asymp- or tomatic Carotid Atherosclerosis Study appears at the rotid sinus, both. The question ad¬ order that could seriously complicate sur¬ end of this article. dressed was: Will CEA added to aggres¬ gery; or a condition that could prevent Reprint requests to Stroke Center and Department of sive reduction of modifiable risk factors continuing participation or was likely to Neurology, Bowman Gray School of Medicine of Wake and Forest University, Medical Center Blvd, Winston\x=req-\ administration of aspirin reduce the produce disability or death within 5 years. Salem, NC 27157-1068 (James F. Toole, MD). 5-year risk of ipsilateral cerebral infarc- (Detailed information regarding eligibil-

Downloaded From: http://jama.jamanetwork.com/ by a University of Rochester User on 01/21/2014 ity and exclusion is available on request randomized using the permuted block patients completed a medical history ques¬ from the corresponding author.) method with at least three different block tionnaire and TIA/stroke questionnaire The ACAS definition of hemodynami- sizes determined randomly, stratified by and underwent physical and neurological cally significant carotid stenosis required center, gender, number of eligible arter¬ examinations and a Mini-Mental State Ex¬ that at least one ofthree criteria was met: ies, and previous contralateral CEA. The amination.17 Risk reduction management arteriography within the previous 60 days assignment category was communicated was reviewed and aspirin adherence was indicating stenosis of at least 60% reduc¬ to each clinical center by the statistical determined by pill count. tion in diameter (if the arteriogram was coordinating center through an individu¬ Doppler ultrasound studies were re¬ performed 61 to 364 days before random¬ alized computer program arranged so peated at the 3-month follow-up, every 6 ization, Doppler ultrasonography was re¬ that the clinical center could neither pre¬ months thereafter during the first 24 quired to verify that the artery had not dict nor reject an assignment. months, then yearly, and at potential or examination within the verified end or at exit from the occluded); Doppler Medical Treatment point preceding 60 days showing a frequency or study after 5 years; CCT was repeated at velocity greater than the instrument-spe¬ All patients received 325 mg ofregular potential end point or exit. Electrocar¬ cific cut point with 95% positive predic¬ or enteric-coated aspirin daily (provided diogram was repeated when clinically in¬ tive value (PPV); or Doppler examination by Sterling Health USA, New York, NY). dicated and at exit. showing a frequency or velocity greater Stroke risk factors and their modification Patients were instructed to notify the than the instrument-specific 90% PPV cut were reviewed with all patients at the coordinator if symptoms suggesting pos¬ point confirmed by ocular pneumople- time of randomization and again during sible TIA or stroke occurred. The co¬ thysmographic (OPG-Gee) examination subsequent interviews and telephone fol¬ ordinator scheduled urgent evaluations performed within the previous 60 days. low-up. This included discussion of dia- by the ACAS neurologist and surgeon, A patient could enter the study with stolic and systolic hypertension, diabetes and activated the end point verification unilaterally or bilaterally asymptomatic, mellitus, abnormal lipid levels, excessive system. hemodynamically significant stenosis, but consumption of ethanol, and tobacco use. In addition to identification of events only one artery was the study artery. If Whenever possible, the recommendations from clinic visits and telephone contacts, two arteries were eligible, the one with ofthe ACAS Risk Factor Reduction Com¬ hospital discharge diagnoses and death the greater stenosis was selected. If the mittee were followed (available on re¬ certificates were reviewed for coronary stenoses were identical, the left carotid quest from the corresponding author). events and strokes. was chosen. Patients randomized artery End Point Definition to on the basis of or Surgical Treatment surgery Doppler and Verification Doppler with OPG-Gee were required to In addition to 325 mg of aspirin daily have an arteriogram prior to CEA. If a and risk factor modification counseling, A TIA was defined as a focal ischemie postrandomization arteriogram revealed patients randomized to the surgical arm neurological deficit of abrupt onset last¬ the contralateral artery to have the received the normal evaluation and care ing at least 30 seconds and resolving com¬ greater stenosis, it then became the study of a surgical patient. They were sched¬ pletely within 24 hours. Deficits persist¬ artery. The nonstudy artery was man¬ uled to undergo CEA within 2 weeks of ing longer than 24 hours were classified aged medically unless a cerebrovascular randomization. If an arteriogram or cra¬ as stroke.18 All strokes or deaths occur¬ event occurred, at which time CEA could nial computed tomogram (CCT) had not ring within 30 days after randomization be considered. been performed, the patient underwent in the surgical and 42 days in the medical the procedure(s) before CEA. The arte¬ groups were included as end points to Measurements Artériographie riogram must have demonstrated a ste¬ reflect operative morbidity and mortal¬ The minimal residual lumen (MRL) nosis of 60% or greater. Patients with a ity. The difference in times reflected an and the distal lumen (DL) were mea¬ postrandomization, presurgery arterio¬ average 12-day interval between random¬ sured on the same radiograph. The MRL gram demonstrating less than 60% ste¬ ization and surgery. was the smallest lumen diameter at the nosis or a distal abnormality such as an- Initial review was conducted under a site of the stenotic lesion. The DL was eurysm, arteriovenous malformation, or stringent timetable involving one exter¬ the diameter at the first point distal to siphon stenosis exceeding the proximal nal expert masked for local diagnosis, the MRL at which the arterial walls stenosis did not undergo surgery but were treatment assignment, clinical center, and became parallel. Percentage of stenosis retained in the surgical arm for compari¬ temporal relationship to surgery (ifdone). was calculated as 100 x (1-[MRL/DL]). son analyses. Asymptomatic cerebral in¬ In addition, every potential event was farction demonstrated by CCT was not abstracted, masked, and reviewed to¬ Ultrasound Measurements an exclusion for surgery.15 No attempt gether by all six experts on the End Point Because of the heterogeneity among was made to standardize or control an¬ Review Committee. Our analyses are ultrasound devices and techniques, we es¬ esthesia or surgical techniques used by based on their diagnoses. tablished a cut point for each by compar¬ the 117 ACAS-credentialed surgeons.16 Secondary analyses considered any ing Doppler ultrasonography with arte- The surgeon, the ACAS neurologist, stroke and perioperative death; any stroke riograms performed within 42 days ofeach and the ACAS patient coordinator ex¬ and any death; and any ipsilateral TIA other. Doppler cut points were computed amined each patient 24 hours after CEA. and stroke and any perioperative TIA, for peak systolic frequency or, ifindeter- All deficits occurring through the 30- stroke, or death. The ACAS used cat¬ minant, end diastolic frequency, based on day perioperative period required the egories 2 through 5 of the Glasgow scale data from 50 consecutive patients.14 administration of the end point review to determine a major stroke, defined as a process (described below). stroke resulting in moderate or severe Randomization disability, persistent vegetative state, or An ACAS neurologist and an ACAS Follow-up death.19 for evaluations were conducted surgeon gave joint approval entering Follow-up Statistical patients. Once the eligibility criteria had at 1 month and thereafter every 3 months, Analyses been confirmed and after informed con¬ alternating between clinic visits and tele¬ Initially, the primary end points for sent was obtained, the patient was phone contacts. During the clinic visit, evaluation of the two treatments were

Downloaded From: http://jama.jamanetwork.com/ by a University of Rochester User on 01/21/2014 Table 1.—Baseline Characteristics of Randomized Table 2.—Artériographie Stenosis of the Ipsilateral Carotid Artery Patients by Treatment Assignment, in Percentages* Prerandomization Arteriogram Treatment I Postrandomization Assignment :-o Stenosis_Medical_Surgical_Total (%)_Presurgery Arteriogram Surgical Medical 0-59_Not applicable_NA_NA_32(8)_ Baseline Characteristic (n=825) (n=834) 60-69_131_137_268(42)_139 (34)_ Age, y 70-79_94_93_187(29)_110(26)_ 40-49 2 2 50-59 13 15 80-89_75_79_154(24)_107(26)_ 60-69 50 46 90-99_13_20_33(5)_24(6)_ 70-79 36 38 Total 313 329 642* 412f Race White 94 95 *Two patients were missing, one in each group. Black 3 3 tTwo patients were missing. Other 3 2 Sex ther resolved the issue ofwhether CEA risk levels are also M 66 66 group-specific pro¬ F 34 34 prevents unheralded cerebral infarction. vided for calculation of absolute risk re¬ History Therefore, in March 1993, the ACAS duction. For the primary event the num¬ 69 Coronary artery dlseaset 69 Executive Committee and the Data and ber of treated to one Hypertension:): 64 64 patients prevent Cancer 12 10 Safety Monitoring Committee voted to event over 5 years was calculated as the Diabetes mellitus 25 21 restrict the primary end point to stroke inverse of the absolute risk reduction.26 disease at 6 5 Lung entry and or Intention-to-treat were used Current cigarette smoker 28 24 perioperative complications analyses Bilaterally eligible arteries 10 death. for all comparisons unless otherwise in¬ Previous contralateral For baseline comparisons, we used two- dicated, regardless of postrandomization 20 19 Endarterectomy tailed t tests for the means of crossover. End for TIA or stroke§ 22 27 comparing ineligibility or points EC-IC bypass <1 0 continuous variables and 2 for compar¬ medical patients who received CEA af¬ Subclavlan bypass <1 <1 distributions of ter verified end were cat¬ Bruits In ing categorical variables, ipsilateral point neck]| with no for as Ipsilateral 76 74 adjustment multiple compari¬ egorized perioperative ifthey occurred Contralateral 44 42 sons. Kaplan-Meier estimates of 5-year within 30 days of CEA. AU tests were Infarct on CT scann risk were between two tailed. Any location 22 24 aggregate compared silent 9 treatment groups either Green¬ Ipsilateral using COHORT Contralateral occlusion wood's formula for variances, for a CHARACTERISTICS 10 large- by Doppler sample testignoringrandomization strati¬ During the 6 years ofthe study, more *TIA indicates transient ischemie attack; EC-IC, exter¬ fication,22 or randomization tests, respect¬ than 42 000 patients were screened and nal carotid-internal carotid; and CT, computed tomographic. ing randomization strata.23 In the initial 1662 patients were randomized. tDefined as of Twenty- positive history angina, coronary artery of treatment 1991 four contributed more than bypass, previous myocardial Infarction, or abnormal elec¬ years comparison, centers 30 trocardiogram. through 1993, the tests were for 2-, 3-, or patients each, and 13 contributed more ÍPositive response to "Has your doctor ever told you risk. The randomiza¬ than 50 The number that you had high blood pressure or were hypertensive?" 4-year aggregate patients. average §Significant difference between groups at .05 level tion test was the primary method for in¬ of patients recruited per center was 43. (unadjusted for multiple comparisons). terim treatment comparisons (see From March 1988 October ¡Bruit question not evaluated for 51 surgical and 52 below). through medical patients. Ipsilateral/contralateral refers to ran¬ By the time of study closure values 1993, 12080 CEAs were performed at domized artery. from the two methods agreed within the sites. Six were scan was not available on 71 and 60 .002, percent (683) per¬ HCT surgical so that all results and on medical patients. test confidence in¬ formed "likely eligible nonrandom- tervals (CIs) reported are based on large- ized" patients of ACAS physicians, 6% ipsilateral TIA, stroke, or any periopera¬ sample tests unless otherwise noted. (758) were performed on already ran¬ tive TIA, stroke, or death. The primary Semiannual treatment comparison anal¬ domized ACAS patients, and the rest analysis is the comparison of the 5-year yses were used to advise the Data Safety were performed on symptomatic pa¬ risk of cerebrovascular events in the two and Monitoring Committee whether a sig¬ tients, ineligible patients, or patients of groups. Because both treatments were in nificance boundary had been crossed. The surgeons not collaborating in the ACAS. wide use, a two-sided test ofthe null hy¬ stopping rule was a modified O'Brien- Patient characteristics are presented pothesis (a=.05) was chosen. Power cal¬ Fleming24 rule for mamtaining the desired in Table 1. Of the 1662 randomized pa¬ culations included all randomized patients overall significance level despite repeated tients, three in the surgery group were according to original treatment assign¬ testing. The modification was for testing lost to follow-up after randomization and ments (intention-to-treat analysis). As¬ at selected intervals rather than prede¬ are excluded from analysis, leaving 1659. suming an annual event rate in the worse- termined numbers of events. The five The 825 surgical and 834 medical patients outcome group of 3% for TIA and 1% for analyses originally planned were changed were compared for 189 baseline charac¬ cerebral infarction, these calculations in¬ to 10, because recruitmentlagged and TIA teristics, with only six tests yielding nomi¬ dicated that 750 patients were needed in was deleted as a primary end point. The nal statistically significant differences at each treatment arm for 90% power to critical value for the test statistic was 6.00 the .05 level. Two thirds of the patients detect a 35% difference in 5-year event at the first test and 2.07 for the 10th, as were men, 95% were white, and 48% were rates, allowing for as much as 20% loss to compared with 1.96 for a single test at the aged 60 through 69 years. Mean age was follow-up. significance level .05. The study was 67 years; mean weight, 81 kg for men and The results of the Veterans Affairs stopped after the eighth test, when the 67 kg for women; mean systolic blood trial20 demonstrated that CEA is pref¬ critical value was 2.38, corresponding to a pressure, 146 mm Hg; mean diastolic blood erable to medical management for pre¬ nominal significance level of .017. pressure, 78 mm Hg; and mean total cho¬ venting TIA in asymptomatic carotid Treatment comparisons are reported lesterol concentration, 5.90 mmol/L (228 stenosis, and the North American Symp¬ herein in terms of relative risk reduc¬ mg/dL). Approximately 75% of patients tomatic Carotid Endarterectomy Trial21 tion, the 5-year risk reduction due to had a bruit associated with the study ar¬ demonstrated that infarction following surgery as a proportion of risk in the tery, and in 43%, a contralateral carotid TIA is better managed surgically. Nei- medical group.25 Absolute treatment bruit was heard; 21% had a previous myo-

Downloaded From: http://jama.jamanetwork.com/ by a University of Rochester User on 01/21/2014 Table 3.—Number of Observed Events in Median 2.7-Year Follow-up, Estimated Number and Percentage of Events in 5 Years, Reduction Due to Surgery in 5-Year Risk as a Proportion of Risk in the Medical Group (95% CI), and Large-Sample Value for Treatment Group Difference, by Event Type* Medical (n=834) Surgical (n=825) I Reduction Due Observed Kaplan-Meier Observed Kaplan-Meier to Surgery in 5-y Risk No. of Events Estimate of 5-y No. of Events Estimate of 5-y as a Proportion of Risk in Median 2.7-y Event Risk, in Median 2.7-y Event Risk, in Medical Group Event Type Follow-up No. (%) Follow-up No. (%) (95% CI) Ipsilateral stroke or any perloperative stroke or death 52 92(11.0) 33 42(5.1) 0.53 (0.22 to 0.72) .004 Major Ipsilateral stroke or any perloperative major stroke or death 24 50 (6.0) 28 (3.4) 0.43 (-0.17 to 0.72) .12 Ipsilateral TIA or stroke or any perioperative TIA or stroke or death 102 160(19.2) 55 67 (8.2) 0.57 (0.39 to 0.70) <.001 Any stroke or any perioperative death 86 146(17.5) 60 102(12.4) 0.29 (-0.05 to 0.52) .09 Any major stroke or perioperative death 40 76(9.1) 28 53 (6.4) 0.30 (-0.30 to 0.62) .26 Any stroke or death 155 266(31.9) 127 211 (25.6) 0.20 (-0.02 to 0.37) .08 Any major stroke or death 213(25.5) 100 171 (20.7) 0.19 (-0.08 to 0.39) .16 *CI Indicates confidence interval; and TIA, transient ischemie attack.

cardial infarction, and 21% a previous gery because of severe cardiac disease. mittee diagnosis and the local physician coronary artery bypass. Sixty-four per¬ Three had a stroke or died before arte- diagnosis. These events included six cent had hypertension, 26% were ciga¬ riography or surgery was performed. Ar- hemorrhagic strokes, two cerebral in¬ rette smokers, and 23% had diabetes mel- teriograms found 33 patients to be ineli¬ farctions in the distribution of the ran¬ litus. gible, six because of intracranial abnor¬ domized artery, three cerebral infarc¬ Four hundred seven patients (25%) malities and 27 because of less than 60% tions in the nonrandomized distribution, had had a previous hemispheric event carotid artery stenosis. Eight patients did and five deaths not due to stroke. contralateral to the and not have surgery for various other rea¬ study artery, Treatment 1155 (70%) were asymptomatic in the sons. Of the 834 patients randomized to Comparisons distribution of both arteries. medical treatment, 45 received CEA with¬ The study achieved its significance Thirty-nine percent of patients were out a verified ipsilateral TIA or stroke. boundary after a median of 2.7 years of randomized on the basis of an arterio¬ Thus, 146 (9%) patients did not receive follow-up, with 9% ofpatients having com¬ gram showing at least 60% stenosis ofthe the assigned treatment. Eleven patients pleted 5 years; 26%, 4; 44%, 3; 68%, 2; and carotid artery. Fifty-five percent were dropped out from follow-up in the medi¬ 87%, 1 year of follow-up. Because surgi¬ randomized with a Doppler PPV cut point cal and nine in the surgical group. cal patients were at greatest risk during ofat least 95%, and 6% with a Doppler cut During the perioperative period, 19 sur¬ the first month after endarterectomy, point of at least 90% confirmed by OPG- gical patients (2.3%) had a stroke or died. whereas the risk for medical patients was Gee. The positive predictive value ofDop¬ Two patients had a stroke, one died prior distributed throughout 5 years, compari¬ pler, estimated from the postrandomiza- to hospitalizaron, and five had a cerebral sons near term greatly understated the tion presurgery angiogram, was 93%. infarction as a direct result of arteriog- differences expected after 5 years. Table Table 2 shows the distribution of per¬ raphy, one of whom died. There were 10 3 presents the observed number ofevents centage of stenosis for prerandomiza- nonfatal strokes and one fatal myocardial and also the Kaplan-Meier estimates pre¬ tion and postrandomization arteriograms infarction during the 30-day postsurgery dicted ifall patients had been followed for before CEA. Because the health status period. In the comparable perioperative 5 years. The estimated 5-year risk of ip¬ of patients who received prerandomiza- period for the medical group, three pa¬ silateral stroke and any perioperative tion arteriograms may differ from that tients (0.4%) had a cerebral infarction (two stroke or death was 11.0% for the medical of those who did not, a weighted esti¬ patients) or died (one patient). For the group and 5.1% for the surgical group. mate based on both categories is in¬ surgical group, the risk in the periopera¬ The reduction in 5-year ipsilateral stroke cluded. Five percent ofpatients had ste¬ tive period was 2.3% (95% CI, 1.28% to risk in the surgical group was 53% of the nosis of the randomized artery less than 3.32%), whereas for the medical group it estimated 5-year risk in the medical group 60%; 39%, 60% to 69% stenosis; 28%, was 0.4% (95% CI, 0.0% to 0.8%). (95% CI, 22% to 72%). The value for the 70% to 79% stenosis; 25%, 80% to 89% All patients randomized to the surgical test of the difference between the treat¬ stenosis; and 5%, 90% to 99% stenosis, group were required to have arteriogra- ment groups in 5-year risk of primary for a mean percentage of stenosis of 73%. phy. Of the 414 patients who underwent event was .004 by the large-sample test The Central Reading Center classified arteriography prior to CEA, five expe¬ and the randomization test. For the pri¬ 536 baseline CCTs15 as showing cerebral rienced a cerebral infarction, for an ar¬ mary end point of ipsilateral stroke and infarction. If an infarcì was present, it tériographie complication rate of 1.2%. It any perioperative stroke or death, the was further classified by age, size, dis¬ is estimated that if all 724 patients re¬ survival curves in the Figure cross near tribution, and volume. Local and central ceiving CEA had undergone arteriogra¬ 10 months and become significantly re¬ readers agreed on 89% of the cases. Us¬ phy as a part of the ACAS, 8.7 artério¬ duced in the surgical group by 3 years ing the Central Reading Center as the graphie cerebral infarctions would have (P<.05). standard, the sensitivity of local reading occurred in addition to the 11 primary The results for secondary end points was 71% and the specificity was 94%. events in the 30 days following surgery, are in the same direction although not for an overall rate of 2.7% for cerebral always statistically significant (Table 3 RESULTS infarction or death from the procedure. and Figure). Ipsilateral TIA or stroke or Ofthe 825 surgical patients, 101 did not Sixteen fatalities, potentially due to any perioperative TIA, stroke, or death— have ipsilateral arteriography or CEA, strokes, were reviewed by the Cere- the original primary end point for the 45 because ofpatient refusal despite prior brovascular End Point Review Commit¬ ACAS—showed a 57% reduction in 5-year agreement to accept either treatment. tee. In no case was there a difference risk for the surgery group (95% CI, 39% Twelve patients were rejected for sin·- between the End Point Review Com- to 70%). In terms of any stroke or death,

Downloaded From: http://jama.jamanetwork.com/ by a University of Rochester User on 01/21/2014 Table 4.—Number of Deaths, Overall and by Treatment Group, in the ACAS, December 1987 Stroke or Perioperative Any Stroke or Ipsilateral December 31, 1994* Death or Stroke Perioperative Death Through Treatment Group I I Cause of Death Surgical Medical Perioperative only 3 1 Ipsilateral stroke 2 3 0.8 Stroke on contralateral side or posterior circulation 1 2 Cerebral hemorrhage 3 4 Acute myocardial infarction 21 24 0.7 Other cardiac disease 15 24 Other vascular disorder 1 2 Respiratory failure 10 9 Cancer 15 13 Tuberculosis 1 0 e Major Ipsilateral Stroke or Any Perioperative Any Major Stroke or o Renal failure 2 ¬ Major Stroke or Perioperative Death Perioperative Death Gastrointestinal system disease 4 3 Nervous system disease 1 0 Trauma 2 0 0.9 Unknown 0 2t Total Deaths 83 Deaths per 100 person-years of 3.5 3.8 0.8 0.8 follow-up *ACAS indicates Asymptomatic Carotid Atheroscle¬ rosis Study. 0.7 0.7 tOne patient died at home, the other at a non-ACAS facility. The patient coordinators were unable to obtain I information as to the causes of deaths.

Ipsilateral TIA or Stroke or Perioperative Any Stroke all had an arteriogram performed before TIA or Stroke or Death or Death so the risk of stroke from 1.0-K 1.0 randomization, undergoing an arteriogram was not in¬ cluded in the calculations. If a 1.2% ar¬ teriogram risk were added to the sur¬ gery groups at the three stenosis levels, the risk reductions become 0.35,0.49, and 0.13, respectively, which are consistent with the overall results of the ACAS. COMMENT The ACAS was designed to test the of CEA for Years of Follow-up efficacy preventing ipsilat¬ eral stroke during a 5-year period. Even this report includes patients fol¬ of without end at a time treatment though Proportion patients point given during follow-up, by group, using Kaplan- lowed for a median of 2.7 Meier estimation method. Solid line indicates medical patients; broken line, surgical patients; and TIA, tran¬ up only years, sient ischemie attack. with 9% having completed 5 years of fol¬ low-up, the data demonstrate a statisti¬ the surgery group had a 20% reduction in not shown). Table 5 shows a larger risk cally significant (P=.004) difference be¬ events (95% CI, -2% to 37%). The reduc¬ reduction due to CEA for younger pa¬ tween the estimated 5-year ipsilateral tion due to CEA in majoripsilateral stroke tients, but the difference is not statisti¬ stroke rates of 11.0% for the medical and or perioperative death was 43% (95% CI, cally significant (P=.50). 5.1% for the surgical group. Moreover, -17% to 72%). Table 4 shows the causes Reanalysis excluding the 146 cross¬ the results are in the same direction for of death were similar for the two groups, overs, ie, restricted to those patients who all subgroups considered, including deciles except for death not proved to result from received the assigned treatment, shows of stenosis (although not statistically sig¬ myocardial infarction. that surgery reduced 5-year stroke risk nificant because ofsmall sample size), and Table 5 summarizes results for ipsilat¬ by 55% (95% CI, 23% to 74%). Alterna¬ for various secondary cerebrovascular end eral stroke or any perioperative stroke or tively, for the 1155 patients who had no points. Furthermore, the results are vir¬ death by patient subgroups. In men, CEA contralateral TIA, stroke, or endarter- tually the same when restricted to all reduced the 5-year event rate by 66% ectomy prior to randomization, surgery patients receiving the assigned treatment, (95% CI, 36% to 82%); in women, the reduced the 5-year stroke risk by 46% and are almost identical for patients with¬ event rate was reduced by 17% (95% CI, (95% CI, 0% to 71%) (Table 5). out previous contralateral symptoms or -96% to 65%). However, the difference The percentage of stenosis for the 642 endarterectomy. between genders was not statistically sig¬ patients who received an arteriogram Approximately 70% ofour medical and nificant (P=.10). The proportion of wom¬ within 6 months preceding randomiza¬ surgical patients had artériographie ste¬ en with perioperative complications was tion is shown in Table 5. Throughout the noses less than 80%. Even so, the esti¬ 3.6%, compared with 1.7% for men CP=.12). three groups, ie, for patients with 60% to mated 5-year ipsilateral stroke rate in However, among patients who had no 69%, 70% to 79%, and 80% to 99% ste¬ the ACAS medical group was 11.0% perioperative event, 5-year risk was re¬ nosis, there was no statistically signifi¬ (about 2.3% annually). The stroke rate duced by 56% for women (95% CI, -50% cant gradation in reduction of 5-year risk in the medically managed group de¬ to 87%), compared with a reduction of of primary event, but sample sizes were creased to the lower end of the previ¬ 79% for men (95% CI, 52% to 91%) (data small. The patients for this comparison ously reported range, perhaps as a re-

Downloaded From: http://jama.jamanetwork.com/ by a University of Rochester User on 01/21/2014 Table 5.—Number and Percentage of Perioperative Strokes or Deaths, Number of Observed Events in Median 2.7-Year Follow-up, Estimated Number and Percentage of 5-Year Ipsilateral Strokes or Perioperative Strokes or Deaths, and Reduction Due to Surgery in 5-Year Risk as a Proportion of Risk in the Medical Group, With 95% CI, by Subgroup* Reduction Due Total Events to Surgery in 5-y Risk as Proportion of Risk Perioperative No. of Events Estimated Eventst in the Medical Group Treatment No. at Events, Observed in Median for 5-y Follow-up, Patient Group Group Risk No. (%) 2.7-y Follow-up No. (%) Estimate 95% CI All Surgical 825 19(2.3) 33 42(5.1) 0.53 0.22 to 0.72 Medical 834 3 (0.4) 52 92(11.0) Men Surgical 544 9(1.7) 22(4.1) 0.66 0.36 to 0.82 Medical 547 3 (0.5) 38 66(12.1) Women Surgical 281 10(3.6) 15 20 (7.3) 0.17 -0.96 to 0.65 Medical 287 0 (0.0) 25 (8.7) Age <68 y Surgical 408 6(1.5) 13 19(4.7) 0.60 0.11 to 0.82 Medical 394 2 (0.5) 23 47(11.8) Age *68 y Surgical 13(3.1) 20 23 (5.5) 0.43 -0.07 to 0.70 Medical 440 1 (0.2) 29 43 (9.7) Bilaterally asymptomatic Surgical 585 12(2.1) 24 32 (5.5) 0.46 0.00 to 0.71 Medical 3 (0.5) 34 58(10.2) Previous contralateral endarterectomy Surgical 240 7 (2.9) 11 (4.5) 0.65 0.13 to 0.86 or TIA or stroke previous Medical 264 0 (0.0) 18 33(12.6) Patients receiving assigned treatment Surgical 724 16(2.2) 37(5.1) 0.55 0.23 to 0.74 Medical 789 3 (0.4) 50 91 (11.5) % Stenosis* 60.0-69.9 Surgical 137 4 (2.9) 9 (6.3) 0.45 -0.70 to 0.82 Medical 131 0 (0.0) 15(11.4) % Stenosis* 70.0-79.9 Surgical 93 1(1.1) 2 (2.2) 0.67 -0.65 to 0.94 Medical 94 0 (0.0) 6 (6.7) % Stenosis* 80.0-99.9 Surgical 99 1 (1.0) 2 (2.0) 0.45 -2.19 to 0.91 Medical 0 (0.0) 3 (3.7)

*CI indicates confidence interval; and TIA, transient ischemie attack. tUsing Kaplan-Meier estimation. ^Percentage of stenosis of randomized artery at baseline, for patients with prerandomization angiogram within 6 months of randomization. suit of vigorous risk factor management consistent with others that established ing less than the required 60%. and exclusion of high-risk patients. that symptomatic patients with carotid If all patients who underwent surgery There were no significant differences stenosis greater than 70% were best had received arteriography as part of the in primary event rates between patient treated by CEA.21^ surgical treatment, the absolute risk re¬ groups with and without symptoms or Because a 10% difference in lumen duction would have been from 11.0% to previous CEA of the contralateral ca¬ diameter on arteriogram is approxi¬ 5.6%. Using ACAS eligibility require¬ rotid artery. With an annual mortality mately 0.5 mm, and the lumen area ste¬ ments, 19 CEAs would be necessary to rate of 3.7%, approximately 89% of pa¬ nosis difference is only 6%, this cannot prevent one stroke over 5 years.25 This tients survived long enough to benefit be measured accurately, and when min¬ ratio would be less if patient subsets at from the protective effect of the opera¬ iaturized images are used, these differ¬ higher risk for stroke could be identified. tion, because the crossover in favor of ences cannot be discerned. Therefore, A CEA can be performed with a low surgery occurred within the first year. we believe that stenoses with 60% and complication rate even in elderly pa¬ Four other randomized prospective 70% reductions in diameter are both tients. In selected instances, some ACAS studies of CEA for asymptomatic ca¬ hemodynamically significant, and that surgeons now operate without arteri¬ rotid artery stenosis have been reported. putative difference by decile is within ography on the basis ofnoninvasive stud¬ One did not include stenosis exceeding the range of observer variability.3032 ies33·34 and sometimes discharge patients 90%,26 another was terminated early be¬ It has been suggested that arteriog- 24 hours following surgery.35 These and cause of excess cardiac events,27 and a raphy should have been required for all other measures may reduce costs if third, the European Asymptomatic Ca¬ ACAS patients to ensure that only those proved generally feasible. rotid is with than 60% stenosis were en¬ Surgery Trial, ongoing.28 greater CONCLUSIONS The fourth, the Veterans Affairs Co¬ tered. However, it was the judgment of operative Trial, randomized 444 patients the ACAS group that the hazards and The ACAS has demonstrated that the and published results based on a mean costs ofarteriography were not warranted incidence of cerebral infarction can be follow-up of 47.9 months. The Veterans for patients in our medical group. This reduced by CEA and that stringent qual¬ Affairs study differed from the ACAS was borne out by the 1.2% stroke rate ity control measures can reduce surgical in that only men were studied and all from arteriography. Our Doppler criteria morbidity and mortality. A major reason patients had an arteriogram.20 were established to maintain a PPV of was the 30-day morbidity and mortality Like the Veterans Affairs trial, the 95%.14 Retrospective analysis of all post- ofACAS patients, estimated to have been ACAS showed an advantage for CEA in randomization, presurgery arteriograms 2.7% if all surgery patients had under¬ preventing TIAs, cerebral infarctions, and demonstrated that our actual PPV was gone arteriography as part of the study. death in men. In addition, the ACAS 93%. This indicates that our medical pa¬ This includes artériographie complications showed an advantage in reducing the risk tients did indeed have significant carotid of 1.2%. These results may be improved ofipsilateral stroke alone. Ourresults are artery stenosis, with fewer than 5% hav- further by reducing risk associated with

Downloaded From: http://jama.jamanetwork.com/ by a University of Rochester User on 01/21/2014 contrast arteriography. The ACAS has MD; Victor J. Celani; Nancy Eckert, RN; James Laura Sauerbeck, RN; L. R. Roedersheimer, MD; Judith established that men with a good life ex¬ Goodreau, MD; Hutchinson, RN; Donna Richard Fowl, MD; John Tew, MD; Richard Kemp- who have carotid Jenny, RN; Zwu-Shin Lin, MD; Alice Madden, RN; czinski, MD; Robert Reed, MD; Richard Welling, pectancy asymptomatic James L. McCullough, MD; Kenneth McDonald, MD; Christine Blum, RN; Bill Schomaker, RN. artery stenosis with at least 60% reduc¬ MD; William Pistone, MD; Alexander D. Rae\x=req-\ Bowman Gray School ofMedicine of Wake For- tion in diameter are protected from stroke Grant, MD; James Redenbaugh, MD; James Rex, est University, Winston-Salem, NC [52]: David by CEA, whereas the results for women MD; Christopher J. Wohlberg, MD. Lefkowitz, MD; J. Michael McWhorter, MD; Charles Marshfield Clinic, Wisconsin L. Jean Robert are less certain. the rela¬ [121]: Percy Branch, MD; Satterfield; Cordell, Following CEA, Karanjia, MD; Mark Swanson, MD; Sandra Lobner, MD; Richard Dean, MD; George Plonk, MD; Gary tive stroke risk reduction for men and LPN; R. Lee Kolts, MD; Marvin E. Kuehner, MD; Harpold, MD; James F. Toole, MD; Francis Walker, women combined is 53%, with an abso¬ Bradley C. Hiner, MD; Kenneth P. Madden, MD; MD; Cathy Nunn, RN RVT; Larry Myers, MBA, lute 5-year risk reduction from 11.0% to Robert D. Carlson, MD; J. Steven Davis, MD; Tho- RDMS, RVT; Charles Tegeler, MD; Sharon Hardin, 5.1%. The reduction in stroke risk mas Gallant, MD; John J. Warner, MD; Ann Faust, RVT, RCMS; Dana Meads, RT-R, RVT. 5-year RVT; Nancy Fryza, RVT; John Hasenauer, RVT; University ofIowa Hospital and Clinics, Iowa among men was 66% and among women Mary Regner, RVT; Linette Ronkin, RVT; Sharon City [49]: Harold P. Adams,Jr, MD; Christopher M. 17%, perhaps because of the higher peri- Schaefer, RVT; Dawn Strack, RVT; Lynn C. Loftus, MD; Lynn A. Vining, RN; Birgette H. Ann operative complicationrateinwomen. Ex¬ Turner, RVT; Walgenbach, RVT; Julie Bendixen, MD, PhD; Jos\l=e'\Biller, MD; John D. Cor- and Graves; Sara Michalski; Linda Schuette. son, MD; Patricia H. Davis, MD; John C. Godersky, cluding artériographie perioperative Columbia University, New York, NY [91]: J. P. MD; David L. Gordon, MD; Michael R. Jacoby, MD; complications, the risk reduction was 79% Mohr, MD; Donald Quest, MD; Annette Cruz; Laurens J. Kappelle, MD; Timothy F. Kresowik, for men and 56% for women. Ralph Sacco, MD; T. K. Tatemichi, MD; Randolph MD; E. Eugene Marsh III, MD; Betsy B. Love, MD; Marshall, MD; Henning Mast, MD; Oscar Ramos, Asad R. Shamma, MD; Karla J. Grimsman, RN; The Asymptomatic Carotid Atherosclerosis Study MD; James Correll, MD; Richard Libman, MD; Dawn M. Karboski, RN; Ed V. Miller, RVT. clinical trial was supported by an investigator\x=req-\ George Petty, MD; Anilda Cabrere, MD; Lorraine Johns Hopkins Bayview Medical Balti- initiated Center, research grant (RO1 NS22611) from the US Oropeza, RN, RVT; Tina Gonzalez. more, Md [46]: Constance Johnson, MD; Calvin Public Health Service National Institute of Neuro- University of Kentucky Chandler Medical Cen- Jones, MD; Brenda Stone, CRNP; Mairi Pat logical Disorders and Stroke. ter, Lexington [88]: Byron Young, MD; Creed Pet- Maguire, RN; Christopher Earley, MD; Peter The authors acknowledge the volunteerism ofall tigrew, MD; Ruthie Sadler, RN; Robert Dempsey, Kaplan, MD; John Cavaluzzi, MD; Gerald Waters, patients in the Asymptomatic Carotid Atheroscle- MD; Eric Endean, MD; Jerry Sherrow, RVT; Mar- PA-C; Betty Chachich, RN. rosis Study. cie Hauer, RN; Charles Lee, MD; Jane Norton; Mi- St John's Mercy Medical Center, St Louis, Mo Funding Agency.\p=m-\National Institute of Neu- chael McQuillen, MD; Sally Mattingly, MD; Steven [44]: Arthur Auer, MD; William Logan, MD; Mary rological Disorders and Stroke, Bethesda, Md: Mi- Dekosky, MD; Andrew Massey, MD. Wilcox, RN, BSN; Barbara Green, MD; Joseph chael D. Walker, MD; John R. Marler, MD; Murray H\l=o^\pitalde l'Enfant Jesus, Qu\l=e'\becCity, Quebec Hurley, MD; Richard Pennell, MD; John Woods, Goldstein, DO; Patricia A. Grady, PhD. [86]: Denis Simard, MD; Jean-Fran\l=c;\oisTurcotte, MD; Richard Levine, MD; James Nepute, MD; Jef- Executive Committee.\p=m-\James F. Toole, MD, MD; Charlotte Benguigui, RN; Jacques C\l=o^\te,MD frey Thomasson, MD; Claire Blackburn, RN, RVT; chair; William H. Baker, MD; John E. Castaldo, (deceased); Jean-Marie Bouchard, MD; Claude Marcia Foldes, BSN, RVT; Kathy Klemp, RN, MD; Lloyd E. Chambless, PhD; Wesley S. Moore, Roberge, MD; Denis Brunet, MD; Fernand B\l=e'\dard; RVT; Becky Nappier, RT, RVT; Karen Ruther- MD; James T. Robertson, MD; Byron Young, MD; R\l=e'\ginaldLangelier, MD; Marcel Lajeunesse; Jean ford, BSN, RVT; Sally Schroer, RN, BSN; Jena Virginia J. Howard, MSPH (ex officio). Marc Bigaouette; Jasmin Parent. Hogan, RN, RVT; Lynne Thorpe, RN, RVT. Executive Committee Liaison.\p=m-\John R. Marler, University of California at San [78]: Pa- Arizona Health Sciences MD. Diego University of Center, trick Lyden, MD; Robert Hye, MD; Stacy Lewis, Tucson [42]: William M. Feinberg, MD; Glenn C. Operations Center.\p=m-\Bowman Gray School of RN; Gerry Cali, RN; Traci Babcock, RN; Barbara Hunter, MD; Denise C. Bruck, AAS; Victor M. Medicine of Wake Forest University, Winston\x=req-\ Taft-Alvarez, RN; John Rothrock, MD; Mark Bernhard, MD; Kenneth E. McIntyre, MD; L. Philip Salem, NC: James F. Toole, MD; Virginia J. Brody, MD; Richard Zweifler, MD; Mark Sedwitz, Carter, MD; Scott S. Berman, MD; Joseph L. R. Howard, MSPH; Suzanne Purvis; Dee Dee Vernon; MD; Bruce Stabile, MD; Julie A. Freischlag, MD; Mills, MD; Enrique L. Labadie, MD; Darry S. Kelley Needham; Pam Beck; Marty Dozier; David Yehuda G Wolf, MD; James Sivo; John Forsythe; Johnson, MD; Constantine G. Moschonas, MD; Rob- S. Lefkowitz, MD; George Howard, DrPh; John R. Melody Adame. ert H. Scott C. Joachim Crouse Hamilton, MD; Forrer, MD; III, MD; David M. Herrington, MD; Curt D. Loyola University Medical Center, Maywood, F. Seeger, MD; Raymond F. Carmody, MD; Brenda Furberg, MD, PhD; Karla Essick; Ralph M. Hicks, Ill [77]: William H. Baker, MD; Sudha Gupta, MD; K. Void, RN, BSN; Richard L. Joan E. La- MEd. Carlson; Jr, MA, Katy Burke; Howard P. Greisler, MD; Fred N. guna; John P. Krikawa; Jenifer J. Devine, RN, BSN, Statistical Coordinating Center.\p=m-\University of Littooy, MD; Michael A. Kelly, MD. RVT; Amalia M. L. North Castrillo; Sheryl Kistler, RN, Carolina at Chapel Hill: Lloyd E. Chamb- University ofTennessee, Memphis [74]: James T. RVT; Betty Ledbetter; Kathleen (Sue) Dorr. less, PhD; J. J. Nelson, MSPH; Will Ball; Ernestine Robertson, MD; William Pulsinelli, MD; Judith A. of Medical Jack- Sean University Mississippi Center, Bland; Condon, MS; Thomas Elliott, MS (de- Campbell, RN, BSN; John Crockarell, MD; Clarence son [39]: Robert R. Smith, MD; Armin F. Haerer, ceased); James E. Grizzle, PhD; Dick Hayes, MCJ; Watridge, MD; J. Acker, MD; Samard Erkulwater, MD; Robin L. Brown, RN, BSN; William Russell, Scott Henley; Jeffrey Johnson, MSPH; James MD; Michael Jacewicz, MD; Gail Walker; Patrick MD; Edward Rigdon, MD; Robert Rhodes, MD; Locklear, MS; Margaret S. Misch, MS; Catherine C. O'Sullivan, MD; Curtis Sauer, MD; Ken Vasu, MD; Evelyn Smith, RVT; Michael Graeber, MD; David Paton, MSPH; Skai Schwartz, MA; Climmon Kenneth Gaines, MD; Bijan Bakhitian, MD; Tulio E. Doorenbos, MD; S. H. Subramony, MD; David L. Walker; O. Dale Williams, PhD. Bertorini, MD; Susan Bennett, PA-C; Terrye Tho- Gordon, MD. Data and Safety Monitoring Committee.\p=m-\ mas, BSN; Nan Stahl, RN; Connie Taylor, RN; Mary Milton S. Hershey Medical Center, Hershey, Pa J. Donald Easton, MD, chair; Jerry Goldstone, MD; Ann Giampapa; Joan Connell; Judy Riley; Angeleah Robert G. Robert W. John [35]: Atnip, MD; Brennan, M. Hallenbeck, MD; Julian T. Hoff, MD; Her- Bradley; Jeanette Davis, RN; Kathy Newman; Re- MD; Diane Friedman, RN, MSN; Marsha M. Neu- bert R. Richard A. PhD. Karp, MD; Kronmal, becca Manning; Marcella McCrea. myer, RVT; Brian L. Thiele, MD; Florence Smith, Cranial Computerized Tomography Reading University Hospital, London, Ontario [63]: RN; John D. Barr, MD; R. Bradford Duckrow, MD; Center.\p=m-\Universityof Cincinnati (Ohio): Thomas Vladimir Hachinski, MD; Gary Ferguson, MD; Jon W. Kevin G. Cindy Janesky, MD; Meilstrup, MD; Brott, MD; Thomas A. Tomsick, MD; Joseph Cheryl Mayer, RN; Henry J. M. Barnett, MD; S. J. P. McNamara, MD; Lawrence D. Rodichok, MD; Broderick, MD; Laura Sauerbeck, RN; Christine Peerless, MD; A. M. Buchan, MD; Howard Reich- Leslie Stewart, MD; Maureen Sullivan, MD; Mark Blum, RN. man, MD; Andrew Kertesz, MD; Stephen Lownie, Wengrovitz, MD. Cerebrovascular End Point Review Commit- MD; Carole White, RN; Allan Fox, MD; Richard University ofTexas Southwestern Medical Cen- tee.\p=m-\MarkDyken, MD, chair; John C. M. Brust, MD; Rankin, MD. ter, Dallas [35]: G. Patrick Clagett, MD; Hal Unwin, Arthur R. Dick, MD; Robert A. Gotshall, MD; Albert Victoria Hospital, London, Ontario [61]: J. MD; Wilson Bryan, MD; Chris Matkins; Carolyn Heyman, MD; Phillip D. Swanson, MD. David Spence, MD; H. W. K. Barr, MD; Leslie Patterson; Candy Alway, RDMS; Patty Boyd; Publications Committee.\p=m-\JamesF. Toole, MD, Paddock-Eliasziw, RN; L. J. P. Assis, MD; J. H. W. Mary Inman, RN; Christie Albiston; Eva Scoggins; chair; Harold P. Adams, Jr, MD; Lloyd E. Chamb- Pexman, MD; Maria DiCicco, RVT; Barb Tate, RN; John Robert Swilling. less, PhD; Dempsey, MD; Calvin B. Ernst, Caroline James, RVT. University of California at Los Angeles [35]: MD; John Rothrock, MD (with special appreciation Virginia Mason Clinic, Seattle, Wash [57]: Ed- Wesley S. N. to N. Moore, MD; Stanley Cohen, MD; Stanley Cohen, MD, for desk editing). mond Raker, MD; James Coatsworth, MD; Sandy Kathleen G. Walden, RN; Samuel S. Ahn, MD; Ed- Participating Centers (in order ofnumber ofpa- Harris, RN; Hugh Beebe, MD; Richard win C. J. Dennis tients Birchfield, Amos, MD; Baker, MD; Bruce H. randomized, number ofpatients in brackets, MD; Kathy Butler-Levy; Robert Crane, MD; David Dobkin, MD; Carlos E. Julie and listed in the Donayre, MD; A. personnel following order: Princi- Fryer, MD; James MacLean, MD; Laird Patterson, Freischlag, MD; Hugh A. Gelabert, MD; Sheldon E. pal Investigator, Co-Investigator, Coordinator, and MD; Terence Quigley, MD; John Ravits, MD; Jordan, MD; Herbert I. Machleder, MD; William J. Other Key Personnel, Current and Past) Lynne Taylor, MD; Stacy Pullen, RDMS; Shannon Quinones-Baldrich, MD; Jeffrey L. Saver, MD; Lehigh Valley Hospital, Allentown, Pa [142]: Boswell, RDMS; Karen Kenny, RDMS, RVT. Suzie M. Richard C. John El-Saden, MD; Holgate, MD; Castaldo, MD; Gary Nicholas, MD; Joan University ofCincinnati Ohio [55]: Thomas Brott, Bradley A. J. Bruce Peter Jabour, MD; Jacobs, MD; Longenecker; Barbour, MD; Alan Berger, MD; Joseph Broderick, MD; Thomas Tomsick, MD; Theresa M. Abraham, RN; Candace L. Vescera,

Downloaded From: http://jama.jamanetwork.com/ by a University of Rochester User on 01/21/2014 RN; Jeanine A. von Rajcs, RN; Vicki L. Carter, Donna Atkins, RN; Phyllis B. Turner, RN, RVT; J. the indications for carotid endarterectomy. Sur- RN, RVT; Dale T. Carter, RVT; De Ette Dix-Goss, Gordon Burch, MD; Donald B. Nolan, MD; Renee gery. 1988;104:932-933. RVT; Eugene C. Hernandez, RVT. Speese; Candace D. Foley, RN. 13. The Asymptomatic Carotid Atherosclerosis Oregon Health Sciences University, Portland Singing River Hospital, Pascagoula, Miss [6]: Ter- Study Group. Study design for randomized pro- [34]: Lloyd Taylor, MD; Bruce Coull, MD; Letha rence J. Millette, MD; Dewey H. Lane, MD; Cynthia spective trial of carotid endarterectomy for asymp- Loboa, RN, RVT; Gregory Moneta, MD; John Por- Almond, RN, RVT; Roland J. Mestayer III, MD. tomatic atherosclerosis. Stroke. 1989;20:844-849. ter, MD; Richard Yeager, MD; Lucy Whittaker, RN. California Pacific Medical Center, San Fran- 14. Howard G, Chambless LE, Baker WH, et al. A Yale University, New Haven, Conn [34]: cisco [4]: Phillip Calanchini, MD; Robert Szarnicki, multicenter validation study of Doppler ultrasound Lawrence M. Brass, MD; Richard J. Gusberg, MD; MD; Pat Radosevich; Linda Elias; Peggy McCor- versus angiogram. J Stroke Cerebrovasc Dis. 1991; Anne M. Lovejoy, PA-C; Pierre B. Fayad, MD; mick; Charles Gould, MD; Forbes Norris, MD; Eric 1:166-173. Bauer Sumpio, MD, PhD; George H. Meier, MD; Denys, MD; Robert Bernstein, MD; Donna Du- 15. Brott T, Tomsick T, Feinberg W, et al, for the Vicky M. Chang, ANP, MSN; Karen Marzitelli, bono; Keith Atkinson; Mark Peters. Asymptomatic Carotid Atherosclerosis Study In- ANP, MSN; Douglas Chyatte, MD; Lynwood Ham- Northwestern University Medical School, Chi- vestigators. Baseline silent cerebral infarction in mers, DO; Fran Lepore, RDMS, RT; Frank J. cago, Ill [4]: Bruce Cohen, MD; James Yao, MD; the Asymptomatic Carotid Atherosclerosis Study. Pavalkis, PA-C; Jill Mele; Donna Kisiel, PA-C. Susan Roston, RN; Donna Blackburn, RN; Jos\l=e'\ Stroke. 1994;25:1122-1129. University of Arkansas for Medical Sciences, Biller, MD; Jeffrey Saver, MD; Linda Chadwick, 16. Moore WS, Vescera CL, Robertson JT, Baker Little Rock [32]: Robert W. Barnes, MD; Michael Z. RN; Douglas Chyatte, MD; Walter McCarthy, MD; WH, Howard VJ, Toole JF. Selection process for Chesser, MD; R. Lee Archer, MD; Bernard W. William Pearce, MD; Jeff Frank, MD; Ernesto surgeons in the Asymptomatic Carotid Atheroscle- Thompson, MD; Colette MacDonald; Gary W. Bar- Fernandez-Beer, MD; James Patrick, MD. rosis Study. Stroke. 1991;22:1353-1357. one, MD; John F. Eidt, MD; David Harshfield, MD; University of Rochester, New York [3]: Richard 17. Folstein MF, Folstein SE, McHugh PR. 'Mini- David McFarland, MD; Jess R. Nickols, MD; E. Green, MD; Richard Satran, MD; John Ricotta, Mental State': a practical method for grading the Carol Howard, BSN, RN, RVT; M. 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