Outcomes of carotid endarterectomy for asymptomatic stenosis in Sweden are improving: Results from a population-based registry

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1 Outcomes of carotid endarterectomy for asymptomatic stenosis in Sweden are improving: Results from a population-based registry Björn Kragsterman, MD, a Håkan ärsson, MD, hd, a Johan Lindbäck, MSc, b David Bergqvist, MD, hd, a and Martin Björck, MD, hd, a on behalf of the Swedish Vascular Registry (Swedvasc), Uppsala, Sweden Objective: In large randomized trials, carotid endarterectomy (CEA) for asymptomatic stenosis has shown a net benefit compared with best medical treatment. To justify an increased number of procedures for this indication, the perioperative risk of stroke or death must not exceed that of the trials. The aim of this study was to evaluate the outcome in routine clinical practice in Sweden in a population-based study. Methods: The Swedish Vascular Registry (Swedvasc) covers all centers performing CEA. Data on all registered CEAs during 1994 to 2003 were analyzed both for the whole time period and for two 5-year periods to study alterations over time. Four validation procedures of the registry were performed. Medical records were reviewed for both a random sample and a target sample (a total of 12% of the CEAs for asymptomatic stenosis). Swedvasc data were cross-matched with the In-atient-Registry (used for reimbursement) and the opulation-registry (death). Results: A total of 6182 CEAs were registered, 671 being for asymptomatic stenosis. In the validation process, no missed registration of major stroke or death was found. atients with asymptomatic stenosis had, when the whole time-period was analyzed, a perioperative combined stroke or death rate of 2.1%. Outcome improved over time; the combined stroke or death rate decreased from 3.3% (11/330) from 1994 to 1998 to 0.9% (3/341) from 1999 to 2003 (.026). During the second time period, no patient with a perioperative major stroke or death was reported. Conclusions: This extensively validated national audit of CEA for patients with asymptomatic carotid artery stenosis showed results well comparable with those of the randomized trials. The results improved over time. (J Vasc Surg 2006; 44:79-85.) The efficacy of carotid endarterectomy (CEA) in preventing stroke among patients with severe asymptomatic stenosis has been demonstrated in large randomized trials. 1-3 Compared with those operated on for a symptomatic carotid artery stenosis, 4-7 the perioperative morbidity in patients with an asymptomatic stenosis has an even more pronounced influence on the overall benefit of the procedure. On implementing CEA for asymptomatic stenosis, the results in every day clinical practice must be in agreement with the results from the randomized trials. Until 2003 in Sweden, about 12% of the CEAs were performed for asymptomatic stenosis, but after the results from the Asymptomatic Carotid Surgery Trial (ACST) were presented, 2 8 the proportion increased to 20% in To justify this increase in CEA for asymptomatic stenosis, the perioperative results need to be evaluated. The Swedish Vascular Registry (Swedvasc) covers all centers performing CEA in the country. The aim of this study was to audit the perioperative outcome of this procedure for asymptomatic From the Department of Surgical Sciences, Uppsala University Hospital, a and Uppsala Clinical Research Center, University Hospital. b This study was supported by a grant from Gorthon Foundation, Helsingborg, Sweden. Competition of interest: none. Reprint requests: Björn Kragsterman, Section of Surgery, Department of surgical sciences, Uppsala University hospital, SE Uppsala, Sweden ( bjorn.kragsterman@surgsci.uu.se) /$32.00 Copyright 2006 by The Society for Vascular Surgery. doi: /j.jvs stenosis on a population basis. The audit also included validation of the registry. MATERIAL AND METHODS CEA. The Swedish Vascular Registry (Swedvasc) started as a regional registry in 1987 and has had national coverage since 1994, thus including all centers performing CEA in the country (population about 9 million). Data were retrieved on all elective CEAs registered during a 10-year period (1994 to 2003). No combined procedures (ie, with thoracic surgery) or procedures for restenosis were included. In this study, the definition of asymptomatic stenosis excluded all ipsilateral carotid artery events and nonhemispheric symptoms such as posterior circulation events and nonspecific symptoms 6 months. Comparison was made between the cohorts operated on for asymptomatic vs symptomatic stenosis regarding baseline characteristics and perioperative complications (30 days). Data were analyzed during two 5-year periods (1994 to1998 and 1999 to 2003), to study changes over time regarding treatment and outcome of the patients with asymptomatic stenosis. The study received ethics approval from the registry review board, which according to Swedish law has the authority concerning registry data. Swedvasc. Swedvasc contains prospectively registered basic demographic data, risk factors, surgical tech- 79

2 80 Kragsterman et al JOURNAL OF VASCULAR SURGERY July 2006 nique, and postoperative outcome at 30 days. Data on the degree of stenosis, status of the contralateral carotid artery, synchronous procedures, antiplatelet and anticoagulation therapy, or type of anesthesia are not included in the registry. The register has been described in detail previously. 9 ostoperative neurologic deficits are classified as either ipsilateral carotid territory events consisting of (1) transitory ischemic attack (TIA), including amaurosis fugax, (2) transient stroke (deficit 24 hours and 30 days), (3) permanent stroke (deficit 30 days); or as other perioperative neurologic or cerebrovascular events, including all perioperative neurologic events not classified as an ipsilateral carotid territory event, for example contralateral carotid territory events or posterior circulation events. Local nerve injuries, hematomas, and wound infection are registered. Risk factors in Swedvasc have had the same definitions throughout the study-period. Cerebrovascular disease is all present or previous neurologic events (stroke, TIA, or amaurosis fugax); diabetes, treatment with insulin, oral medication, or diet; hypertension, medication or a diastolic blood-pressure 110; cardiac disease, previous myocardial infarction, atrial fibrillation, heart failure, angina pectoris, coronary artery bypass, operation for valvular disease or signs of ischemia on an electrocardiogram; previous vascular surgery, open or endovascular procedure or amputation for vascular disease; renal insufficiency, a serum creatinine 150 mol/l; and smoking, regular smoking 5 years. Validation. All patients were cross-matched with the National opulation-registry, which was possible by the unique personal identity code of every Swedish citizen. This results in 100% accurate data on mortality and date of death. From the cohort of patients operated on for asymptomatic stenosis, we collected complete medical records for both a general and a targeted validation procedure. First, a random sample of approximately 10% of all procedures was identified, using the SSS (SSS Inc, Chicago, Ill) random sample of cases functions. Second, unclear complication registrations were identified in the entire asymptomatic cohort. These included (1) perioperative thrombosis or occlusion and (2) peripheral embolization registered without neurologic complication, as well as those with a registration of (3) cerebrovascular event and also those (4) lacking a registration of 30-day complications (missing field). A fourth validation procedure was performed to evaluate how many CEAs may not have been registered in Swedvasc. ermission was granted from the National Board of Health and Welfare to compare the number of operations in Swedvasc with that of the In-atient Registry (IR) for each hospital for the year The IR is used for reimbursement, and the hospitals have an economic incentive to register their operations in that registry. Unfortunately, we were not granted permission to compare data on the individual level, as cross-matching data registries using the unique personal identity code is restricted by Swedish law. The validation process is also illustrated in the Figure. In the validation process, unregistered or incorrectly registered permanent strokes were also classified into minor or major strokes in an attempt to evaluate the severity of neurologic deficit in these missed registrations. The classification of functional status was retrospective and based on the data in the medical records. Minor stroke was defined as minimal focal neurologic deficit persisting 24 hours but not leading to disability or significant impairment in activities of daily living. Major stroke was defined as a deficit lasting 30 days and inducing a change in lifestyle. Statistics. Analyses were done using SSS and R 2.2 (R-roject for Statistical Computing, Vienna, Austria) 10 Continuous variables were summarized by the -me dian (and quartiles), and categoric variables were summarized by percentages. Continuous variables were compared with the Wilcoxon-Mann-Whitney test and categoric variables with the earson 2 test. Analyses of risk factors for the different combined outcomes (listed in Table I) were performed using multiple logistic regression models. The selected model was designed based on the number of adverse events, the completeness of the variables in the database, and on the clinical relevance. As the numbers of adverse evens were small, the numbers of variables that may be included in the model were limited (recommended to be one variable per 10 events) Results are presented as odds ratios (OR) with 95% confidence intervals (CI). A statement of statistically significant implies a.05. RESULTS Validation. In the cross-match with the National opulation-registry, all perioperative deaths had been reported to the Swedvasc. Complete medical records were obtained for 82 (89%) of 92 of the random sample and target validation, and in reviewing the records we found two permanent strokes and two transient strokes incorrectly registered, and one transient stroke and one TIA not registered (Table II) The two incorrectly registered permanent strokes were considered as minor strokes, according to the severity classification (in Methods). During 2003, 771 CEAs were registered in Swedvasc and 782 patients in the IR. Three hospitals had exactly the same number of procedures in both registries; 10 had more in Swedvasc and eight had more in the IR. In those latter eight hospitals, 32 surplus operations were registered in the IR. A total of 4.1% (32/782) of those in the IR were unregistered in Swedvasc. (Cross-match on individual level was not permitted see Methods) The registry was corrected regarding complications before the analysis within the asymptomatic cohort. In comparison with the (uncorrected) symptomatic cohort, both the uncorrected and corrected data were presented. Thus, we did not identify any unregistered death or major stroke in the validation process. CEA. CEA was performed in 22 of 44 vascular units reporting to the registry, and of these, five did not operate on patients with asymptomatic stenosis. During this 10-

3 JOURNAL OF VASCULAR SURGERY Volume 44, Number 1 Kragsterman et al 81 Fig. The four different validation procedures of the Swedvasc registrations for carotid endarterectomy (CEA) of asymptomatic stenosis. year period (1994 to 2003), 6182 carotid endarterectomies on 5821 patients were registered, the numbers with indication asymptomatic stenosis were 671 (10.9%) of 6182 CEAs on 636 (10.9%) of 5821 patients. Bilateral CEAs were performed on 361 (6%) of 5821 patients, of which 152 (24%) of 636 were among patients with at least one asymptomatic stenosis. Operations for bilateral asymptomatic lesions were performed in 35 (6%) of 636 patients. Bilateral operations were staged. Mean age was 70 years (quartiles 64, 75) for both the symptomatic and asymptomatic group. There were no gender differences; men comprised 63.8% of patients with asymptomatic stenosis and 66.6% of those with symptomatic stenosis (.16). The differences in baseline characteristics for the whole time period, with respect to indication, are presented in Table III. The indications for the symptomatic patients were minor stroke in 40%, TIA in 37%, amaurosis fugax in 20%, and nonhemispheric symptoms in 2%. atch closure was performed in 34% for asymptomatic vs 32% for symptomatic lesions (.199). The perioperative morbidity and mortality rates are shown in Table IV, with a combined stroke (permanent and transient) or death rate of 1.6% for (uncorrected) asymptomatic vs 4.3% for the symptomatic group (.001). Two fatal strokes (of 3 deaths) occurred among the procedures for asymptomatic and 17 (of 74 deaths) among those for symptomatic stenosis. Local nerve injury occurred with similar rate for the two groups, with 6.7% for asymptomatic vs 7.0% for symptomatic stenosis (.762). ostoperative bleeding or hematomas were registered for 6.4% of asymptomatic vs 6.4% of symptomatic lesions (.506). The wound infections rates were 0.6% for the asymptomatic vs 0.9% for the symptomatic indication (.413). Among the patients with asymptomatic stenosis, many were randomized into the ACST. Approximately half of the 532 Swedish patients who were recruited would have been allocated to immediate CEA (266 ACST/671 Swedvasc 40%). CEA for asymptomatic stenosis. Data from the asymptomatic cohort was divided into two 5-year periods (1994 to 1998 and 1999 to 2003). During the first period, 330 operations were performed (12.6% of the total number of CEAs during that time period), compared with 341 procedures (11.7%) during the second. Baseline characteristics were comparable between the two periods, except that hyperlipidemia (.001) and hypertension (.002) were more frequent in the second period (Table V). atch closure was more often used during the second period (28 % vs 40 %,.001). The frequency of eversion endarterectomy increased over time (0.3% vs 5.9%,.001) erioperative morbidity and mortality rates are shown in Table I. There were no deaths and only one permanent (minor) stroke during the second period Multiple regression analysis. Logistic regression analysis was performed testing the factors of age, gender, and patch for different combinations of outcome. When all stroke, TIA, cardiovascular complications, and death were used as outcome in the model, the only significant variable Table I. erioperative morbidity (neurologic and cardiovascular) and mortality for carotid endarterectomy with indication asymptomatic stenosis during the two time periods Complication n n 341 ermanent stroke 1.5% (5) 0.3% (1).093 Transient stroke 1.5% (5) 0.6% (2).238 Stroke (permanent and transient) 3.0% (10) 0.9% (3).044* TIA 0.3% (1) 0.3% (1).983 Cerebrovascular event 1.8% (6) 1.5% (5).723 Death 0.9% (3) 0.0% (0).078 Cardiovascular complication 4.6% (15) 3.8% (13).640 ermanent stroke and death 1.8% (6) 0.3% (1).052 Stroke (permanent and transient), death 3.3% (11) 0.9% (3).026* Stroke, TIA, death 3.6% (12) 1.2% (4).036* Stroke, TIA, cerebrovascular event, death 4.2% (14) 2.3% (8).168 Stroke, TIA, cardiovascular complication, death 7.6% (25) 4.7% (16).119 TIA, Transient ischemic attack. *Indicates significance (.05); earson 2 test.

4 82 Kragsterman et al JOURNAL OF VASCULAR SURGERY July 2006 Table II. Validation of perioperative neurological complication registration after CEA with indication asymptomatic stenosis Validation N patient-records obtained/requested N incorrect registrations Neurologic deficit Classification in registry Classification in validation Random sample 65/71 (93%) 2 1. Minor contralateral finger dysfunction (IV-V) 2. Contralateral facial paresis (corner of Target sample 1. Thrombosis or occlusion; 2/3 2. eripheral embolization; 2/2 3. Cerebrovascular event; 6/9 4. Missing 30-day registration; 7/7 Total 82/92 (89%) 5 mouth) 1 Contralateral arm dysfunction (minutes duration) Transient stroke Local neurology Not registered ermanent stroke ermanent stroke TIA 0 NA NA NA 2 1. Ipsilateral (worsening) arm dysfunction (3 days duration) 2. Contralateral hand/arm dysfunction ( 7 days duration) 1 Contralateral hand dysfunction and aphasia ( 5 days duration) Cerebrovascular event Cerebrovascular event Not registered Transient stroke* Transient stroke Transient stroke TIA, transient ischemic attack; NA, not applicable. Results from a random sample as well as target validation of unclear perioperative complication registrations (see Material and Method). *Ipsilateral stroke but with a contralateral occlusion, most likely a peroperative hypoperfusion injury that should have been registered as a surgical complication (transient stroke). Table III. Baseline characteristics for asymptomatic and symptomatic patients undergoing carotid endarterectomy during 1994 to 2003 Baseline characteristics Asymptomatic stenosis, n 671 (n) Symptomatic stenosis, n 5511 (n) Cerebrovascular disease 62.5% (406) 92.5% (4926)*.001 Diabetes mellitus 19.2% (122) 18.9% (942).864 Hyperlipidemia 54.0% (218) 49.8% (1399).114 Hypertension 65.1% (420) 60.2% (3081).017 Cardiac disease 47.4% (304) 44.7% (2282).184 revious vascular surgery 39.5% (254) 16.5% (829).001 Chronic pulmonary disease 8.6% (55) 8.6% (425).935 Renal insufficiency 6.0% (38) 3.7% (179).004 Smoking 41.4% (251) 42.0% (1956).769 For definitions see Material and Methods. *Among the patients with symptomatic stenosis registered as indication for the procedure, almost all should have the risk factor cerebrovascular disease, if these preoperative registrations were complete and correct. The difference of 7.5% represents, almost unexceptionally, missing fields. Indicates significance (.05), earson 2. identified was age, where an OR of 1.67 (95% CI, 1.11 to 2.50) was found for each SD of 8.3 years (.01), which implies that the patient at age 78.3 has a 67% increased risk compared with the patient at age 70. It can also be described as an OR of 2.85 (95% CI, 1.44 to 5.62) among those 75 years of age. In the same model, women had an OR of 1.45 (95% CI, 0.74 to 2.85) and patch OR of 0.77 (95% CI, 0.37 to 1.59). DISCUSSION The perioperative stroke or death rate for CEA of asymptomatic stenosis in this validated population-based

5 JOURNAL OF VASCULAR SURGERY Volume 44, Number 1 Kragsterman et al 83 Table IV. erioperative morbidity (neurological and cardiovascular) and mortality for carotid endarterectomy for the whole time period (1994 to 2003) Complication Symptomatic stenosis n 5511 (not corrected) (n) Asymptomatic stenosis n 671 (corrected) (n) Asymptomatic stenosis n 671 (n) ermanent stroke 2.1% (113) 0.6% (4).009* 0.9% (6).036* Transient stroke 1.3% (72) 0.9% (6) % (7).544 Stroke (permanent and transient) 3.4% (185) 1.5% (10).009* 1.9% (13).043* TIA 1.3% (73) 0.1% (1).008* 0.3% (2).020* Cerebrovascular event 2.0% (108) 1.8% (12) % (11).545 Cardiovascular complication 2.5% (135) 4.2% (28).009* 4.2% (28).010* Death 1.4% (74) 0.4% (3).048* 0.4% (3).051 ermanent stroke and death 3.1% (169) 0.7% (5).001* 1.0% (7).003* Stroke (permanent and transient) and death 4.3% (239) 1.6% (11).001* 2.1% (14).005* Stroke, TIA, death 5.6% (311) 1.8% (12).001* 2.4% (16).001* Stroke, TIA, cerebrovascular event, death 6.6% (363) 2.8% (19).001* 3.3% (22).001* Stroke, TIA, cardiovascular complications, death 8.3% (460) 6.3% (42) % (46).182 TIA, Transient ischemic attack. *Indicates significance (.05), earson 2 test. Table V. Baseline characteristics for patients with asymptomatic stenosis, divided in two 5-year periods Baseline characteristics n 330 (n) n 341 (n) Age, mean (quartiles) 70 (64;74) 69 (64;75).715 Gender; male 61.8% (204) 65.8% (223).286 Cerebrovascular disease 62.2% (201) 62.7% (205).903 Diabetes 16.4% (52) 21.9% (70).079 Hyperlipidemia 44.4% (79) 61.5% (139).001* Hypertension 59.2% (189) 70.9% (231).002* Cardiac disease 49.1% (156) 45.8% (148).412 revious vascular surgery 40.0% (128) 39.0% (126).797 Chronic pulmonary disease 8.0% (13) 9.3% (30).56 Renal insufficiency 4.2% (13) 7.9% (25).052 Smoking 39.4% (117) 43.4% (134).321 For definitions see Material and Methods. *Indicates significance (.05), earson 2 test; Wilcoxon test for age. study was 2.1% for the whole time period and decreased over time to 0.9% in the second period (1999 to 2003). There was no perioperative death or major stroke after CEA for asymptomatic stenosis during the second time period. The combined stroke or death rate in this national audit compared favorably with the results in previous large randomized trials, as in Asymptomatic Carotid Atherosclerosis 1,2 Study (ACAS) 2.3% and in ACST 2.8%. When all neurologic morbidity (irrespective of duration or side) and mortality was included, the 30-day complication rate was 2.3% in the more recent time period. The perioperative combined stroke or death rate decreased from 3.3% to 0.9% in the second period (.026), and this improved outcome over time is in agreement with other reports. In two recent series, similar results were obtained for patients undergoing CEA for asymptomatic stenosis, while analyzing outcome for different time periods. 11,12 Bond et al 13 recently published a meta-analysis of CEA, where the pooled estimate of the absolute risk of stroke or death decreased for the asymptomatic indication in the more recent articles ( 1995). Comparing baseline characteristics between the patients with asymptomatic and symptomatic stenosis, the high rate of previous vascular surgery (40%) among those with asymptomatic lesions probably reflects how they were often identified, namely when investigated or followed-up for other lesions and procedures (ie, aneurysm, lower extremity ischemia or contralateral symptomatic carotid stenosis). In the asymptomatic cohort, 24% had bilateral operations, contributing to the fact that almost 63% of these patients had cerebrovascular disease registered at baseline as a preoperative risk factor. Others may have symptomatic contralateral occlusion or previous ( 6 months ago) cerebrovascular events of various causes. It is important to bear in mind that these patients represent a highly selected group with atherosclerotic manifestations and may therefore bias the results. However, the potentially negative bias introduced was not clearly reflected in the perioperative outcome in this series. Furthermore, the patients with asymptomatic stenosis had more registered comorbidities (cerebrovascular discussed above) compared with patients who had symptomatic stenoses. The incidence of hypertension and renal insufficiency

6 84 Kragsterman et al JOURNAL OF VASCULAR SURGERY July 2006 were significantly higher in this patient group. In a study of 14 patients with renal insufficiency, Ayerdi et al reported increased perioperative mortality after CEA. Even though most of the baseline characteristics were similar over time for the patients with asymptomatic stenosis, the frequency of hypertension and hyperlipidemia increased during the second period, implying that the improvement in outcome was not due to a favorable difference in case-mix. The increased registration of hyperlipidemia may reflect a more active awareness of this risk factor together with an increased prescription of statins, but the incomplete registrations, especially in the first period, may introduce a bias. Other investigators have reported a protective effect of statins in patients undergoing CEA, 15,16 however, and an increased statin use in the second period could have contributed to the improved outcome. A similar, somewhat contradictory, contribution to the improved outcome may also be explained by hypertension. A more active treatment of this risk factor may reduce both the cerebrovascular and cardiovascular risk. Some concerns have been raised that the advancements in medical treatment may decrease the stroke risk for patients with asymptomatic carotid stenosis, resulting in reduced netbenefit of CEA. However, data from this study suggest that the surgical risk also decreases with contemporary treatment and that the overall outcome may still be in favor of surgery. Improvements in surgical technique may also have contributed to improved results. atch angioplasty is suggested as being beneficial, but that was not confirmed in the present study. A possible explanation may be that although the frequency significantly increased over time, only 40% had patch closure in the more recent time period. Another factor influencing the predictive value may be the small number of adverse events. Eversion endarterectomy gained popularity during this series but still only represents 5.9% of all CEAs during the second period. Furthermore, randomized trials 20,21 have not consistently demonstrated benefit with ever - sion endarterectomy compared with conventional technique. 22 The type of anesthesia was not registered in Swedvasc, so its possible effect on the complication rate could not be addressed. Age was the only significant risk factor in the logistical regression analysis, in agreement with the results from There are limitations and strengths in this study. In analyzing risk factors, the small numbers of perioperative events limit the ability of extensive subgroup or multiple regression analysis. A potential weakness with registry studies (open audit) is self-reported data. Swedvasc is validated in different aspects annually. 8,9,27 CEA has been especially studied on 9,28 several occasions with high accuracy in the registry. In the validation process of this study, which included cross matching against two other registries, random sampling, and targeted validation, we could not identify a single patient with unreported major stroke or death. In this study, many of the asymptomatic patients were included in ACST (40%) and underwent an independent examination by a neurologist at follow-up (30 days). atients at an increasing number of Swedish hospitals have a routine neurologist s examination at 30 days, which is recommended by the Steering Committee of Swedvasc. One of the benefits of an open audit is the possibility to get updated information on changes in practice and results. Vascular surgeons in Sweden have generally been restrictive with CEA for asymptomatic stenosis. Indications for the procedure have most often been based on the degree of stenosis, but other factors (eg, extent of contralateral disease) vary between centers and individual surgeons, and could not be assessed in this study. There has been a stable level of CEAs for asymptomatic patients (11% to 12%) until recently, when this indication increased after the results of 27 ACST were made public (20% and increasing). When changes in practice are implemented on the basis of results from the trials, perioperative complication rates must be regularly assessed. In doing so, the results from this population-based study may justify an increase in carotid endarterectomy for patients with asymptomatic stenosis, also in this routine clinical setting. CONCLUSION The perioperative outcomes in this extensively validated national audit of carotid endarterectomy for asymptomatic stenosis were well comparable with those of the large randomized trials. Furthermore, there were decreasing complication rates over time. AUTHOR CONTRIBUTIONS Goldstein et al 23 who reported significantly higher stroke or death rate for those 75 years. In both ACAS and ACST, those 75 years had a less favorable outcome, 1,2 although not statistically significant. These trials also demonstrate less benefit for CEA of asymptomatic stenosis for women compared with men, partly due to a higher perioperative risk. 1,2 In this series no significant gender differences were noted in the outcome, which is consistent with other reports that have specifically analyzed women 24,25 operated on for an asymptomatic stenosis. In another 26 recent large series of CEAs, Hartun et al reported a REFERENCES higher stroke rate for women in univariate analysis. That difference was lost with multivariate analysis; however, the indication for surgery could not be assessed in their study. 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7 JOURNAL OF VASCULAR SURGERY Volume 44, Number 1 Kragsterman et al MRC Asymptomatic Carotid Surgery Trial (ACST) Collaborative Group. revention of disabling and fatal stroke by successful carotid endarterectomy in patients without recent neurological symptoms: randomized controlled trial. Lancet 2004;363: Hobson RW, Weiss DG, Fields WS, for the Veteran affairs study group. Efficacy of carotid endarterectomy for asymptomatic carotid stenosis. N Engl J Med 1993;328: North American Symptomatic Carotid Endarterectomy Trial Collaborators. Beneficial effects of carotid endarterectomy in symptomatic patients with high-grade stenosis. N Engl J Med 1991;325: North American Symptomatic Carotid Endarterectomy Trial Collaborators. Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. N Engl J Med 1998;339: European Carotid Surgery Trialist s Group. MRC European Carotid Surgery Trial: interim results for symptomatic patients with severe (70-99%) or mild (0-29%) carotid stenosis. Lancet 1991;337: European Carotid Surgery Trialist s Group. Randomised trial of endarterectomy for recent symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST). Lancet 1998;351: Swedvasc Yearly Report Available at: 9. Bergqvist D, Troeng T, Elfström J, Hedberg B, Ljungström K-G, Norgren L, et al. Auditing surgical outcome. Ten years with the Swedish Vascular Registry - Swedvasc. Eur J Surg 1998;164: R Development Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. ISBN ; Kresowik TF, Bratzler DW, Kresowik RA, Hendel ME, Grund SL, Brown KR, et al. Multistate improvement in process and outcomes of carotid endarterectomy. J Vasc Surg 2004;39: Darling RG 3rd, Kreienberg B, Roddy S, aty SK, Chang BB, Lloyd WE, et al. Analysis of the effect of asymptomatic carotid atherosclerosis study on outcome and volume of carotid endarterectomy. Cardiovasc Surg 2000;6: Bond R, Rerkasem K, Rothwell M. Systematic review of the risk of carotid endarterectomy in relation to the clinical indication for and timing of surgery. Stroke 2003;34: Ayerdi J, Sampson LN, Deshmukh N, Farid A, Gupta SK. Carotid endarterectomy in patients with renal insufficiency: Should selection criteria be different in patients with renal insufficiency? Vasc Surg 2001;6: McGirt MJ, erler BA, Brooke BS, Woodworth GF, Coon A, Jain S, et al. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors reduce the risk of perioperative stroke and mortality after carotid endarterectomy. J Vasc Surg 2005;42: Kennedy J, Quan H, Buchan AM, Ghali WA, Feasby TE. Statins are associated with better outcome after carotid endarterectomy in symptomatic patients. Stroke 2005;36: Archie JR Jr. A fifteen-year experience with carotid endarterectomy after a formal operative protocol requiring highly frequent patch angioplasty. J Vasc Surg 2000;31: Rockman CB, Halm EA, Wang JJ, Chassin MR, Tuhrim S, Formisano, et al. rimary closure of the carotid artery is associated with poorer outcomes during carotid endarterectomy. J Vasc Surg 2005;42: Bond R, Rerkasem K, AbuRahma AF, Naylor AR, Rothwell M. atch angioplasty versus primary closure for carotid endarterectomy. Cochrane Database Syst Rev 2004;2:CD Ballotta E, Da Giau G, Saladini M, Abbruzzese E, Renon L, Toniato A. Carotid endarterectomy with patch closure versus carotid eversion endarterectomy and reimplantation: A prospective randomized study. Surgery 1999;125: Cao G, Giordano G, De Rango, Zannetti S, Chiesa R, Coppi G, et al. and Collaborators of the EVEREST Study Group. Eversion versus conventional carotid endarterectomy: late results of a prospective multicenter randomized trial. J Vasc Surg 2000;31: Cao G, De Rango, Zannetti S, Giordano G, Ricci S, Celani MG. Eversion versus conventional carotid endarterectomy for preventing stroke. Cochrane Database Syst Rev 2001;1:CD Goldstein LB, Samsa G, Matchar DB, Oddone EZ. Multicenter review of preoperative risk factors for endarterectomy for asymptomatic carotid artery stenosis. Stroke 1998;29: Rockman CB, Castillo J, Adelman MA, Jacobowitz GR, Gange J, Lamparelo J, et al. Carotid endarterectomy in female patients: are the concerns of the Asymptomatic Carotid Atherosclerosis Study valid? J Vasc Surg 2001;33: Lee J-W, omposelli F, ark KW. Association of sex with perioperative mortality and morbidity after carotid endarterectomy for asymptomatic carotid stenosis. J Cardiothor Vasc Anesth 2003;17: Harthun NL, Kongable GL, Baglioni AJ, Meakem TD, Kron IL. Examination of sex as an independent risk factor for adverse events after carotid endarterectomy. J Vasc Surg 2005;41: Swedvasc Yearly Report Available at: Kragsterman B, Logason K, Ahari A, Troëng T, ärsson H, Bergqvist D. Risk factors for complications after carotid endarterectomy - a population based study. Eur J Vasc Endovasc Surg 2004;28: Submitted Jan 12, 2006; accepted Mar 6, 2006.