Asymptomatic Carotid Surgery Trial Research Articles

Atherosclerotic Peripheral Vascular Disease Symposium II

Carotid artery disease is a major cause of ischemic stroke, the risk of which is directly related to the severity of stenosis and presence of symptoms.1,2 Stroke is the third leading cause of death in the United States, with approximately three quarters of a million strokes per year. Stroke is the leading cause of functional impairment, with more than 20% of survivors requiring institutional care and up to one third having a permanent disability.3 More worrisome, however, is the fact that as the population ages, the number of patients having strokes appears to be increasing.4 The pathophysiology of stroke may be broadly classified as hemorrhagic, embolic, or ischemic. The majority of strokes are caused by embolic events due to atheroemboli from the carotid artery, the ascending aorta, and arch vessels or cardiac thromboembolism from the left atrium or ventricle. It is estimated that carotid artery stenosis is responsible for 15% to 20% of all strokes.5 As percutaneous treatment options expand, there is uncertainty about appropriate therapy for carotid disease. This document will focus on 3 current controversies: (1) carotid artery revascularization in asymptomatic patients, (2) carotid artery stenting (CAS) in patients who are considered to be at increased surgical risk for carotid endarterectomy (CEA), and (3) the current role for CAS in patients at average surgical risk. ### Prevalence and Natural History The prevalence of asymptomatic extracranial carotid stenosis (≥50%) in persons >65 years of age is estimated to be between 5% and 10%, whereas ≤1% of patients are estimated to have a severe narrowing (>80%).6 In asymptomatic patients with ≥50% carotid artery stenoses, the annual risk of stroke is between 1% and 4.3%.2,7 Long-term (10- to 15-year) cohort studies in asymptomatic patients with moderate to severe carotid stenosis demonstrate an ipsilateral stroke rate between 0.9% and 1.1% per …

Cost-Effectiveness of Endarterectomy in Patients with Asymptomatic Carotid Artery Stenosis

Conclusion: In patients with asymptomatic carotid stenosis, carotid endarterectomy, in addition to best medical management, is cost effective in men age 73 years or less. It is unlikely to be cost effective in older men or in women. Summary: Major randomized trials of carotid endarterectomy (CEA) in addition to best medical management compared to best medical management alone have indicated CEA is effective in reducing strokes in the patient populations studied. The cost effectiveness of such a strategy in asymptomatic patients has not been well studied. In this study, the authors investigated the cost effectiveness of CEA for asymptomatic patients in comparison to a strategy of best medical management alone. The authors developed a Markov transition model to model disease progression and use of resources for both CEA combined with best medical management or the strategy of best medical management alone. The model was based on data from the randomized asymptomatic carotid surgery trial (ACST), a National Swedish Vascular Database, and expected costs and health outcomes in terms of quality adjusted life years (QALYs). Cost effectiveness was established for a Swedish setting from the Swedish societal perspective. (Base-case analysis showed incremental cost per QALY of CEA for a 65- and 75- year old man/woman was 34,557 Euros and 311,133 Euros and 58,930 Euros and 779,776 Euros respectively. A sensitivity analysis indicated that a duration of treatment effect of five years was important for the cost effectiveness results. An additional five-year duration of treatment effect (10 years total) indicated that the cost in Euros per QALY gained from CEA was 13,748 for men age 65 years and 31,384 for men age 75 years. For an additional 10 year duration of treatment effect (15 years total) the cost per QALY gained from CEA for a 65 year old man was 8,707 Euros and for a 75 year old man, 26,315 Euros. Fifteen year total treatment effect in women 65 years of age was at a projected cost of 46,421 Euros per QALY and for a woman 75 years of age, it was 114,936 Euros per QALY. Comment: It is estimated 34,557 Euros per QALY gained for a 65 year old man is cost effective. At age 73 years, for men, the cost per QALY gained with CEA was near the implicit willingness to pay for a QALY in Sweden. It indicates that men age ≤73 years of age gain enough from CEA to justify risks of CEA and high initial costs. In women, it is only those 65 years of age or under at the time of CEA and who live 15 years who will benefit from prophylactic CEA from a cost effective viewpoint. The data are obviously interesting but it seems politically untenable to deny women, and not men, prophylactic CEA for high-grade asymptomatic carotid stenosis.

Occult carotid artery disease in patients who have undergone coronary angioplasty

The aim was to evaluate the prevalence of asymptomatic mild (30-49%), moderate (50-69%) and severe (70-99%) ICA stenosis in patients who underwent previous coronary angioplasty (PTA). After obtaining ethics committee approval, 144 consecutive patients aged between 65 and 75 years were invited for carotid Duplex evaluation with a linear 6 MHz array transducer by trained vascular sonographers within a single unit. A peak systolic velocity >230 cm/s in the ICA was considered as significant (>70% stenosis). Of the 144 patients approached, 117 (81%) attended (male:female ratio 3.2:1, age range 65-75 years, median age 71 years). Duplex ultrasound revealed one occlusion, 70% or more ICA stenosis in three patients (2.6%), 50-69% stenosis in 12 patients (10.3%) and 30-49% stenosis in 29 patients (24.8%). Carotid artery disease with a luminal stenosis of 30% or more is common in patients who underwent previous PTA. The yield of significant ICA stenosis (70% or more), which would benefit from carotid endarterectomy according to the Asymptomatic Carotid Surgery Trial is low. Recommendation for initial screening and subsequent follow-up Duplex examination for evaluation of disease progression of such cohorts remains debatable.

Changing trends in surgical treatment of carotid disease in Ireland (1996–2003)

Carotid endarterectomy (CEA) is a well-established method of stroke prevention in patients with symptomatic, high-grade internal carotid artery stenosis. To assess the change in carotid surgery practice in health board regions in Ireland over two different time periods in the past 11 years (1996-1998/2001-2003). Numbers of discharges of patients with a procedure code CEA (38.12) between 1996-1998 and 2001-2003 were obtained from the Hospital In-Patient Enquiry (HIPE) database maintained by the Economic and Social Research Institute (ESRI). Population data was obtained from national censuses. There has been considerable change in the level of carotid surgery activity in specific health board regions between the two periods. Still no region comes close to achieving levels of CEA recommended by population studies. This is important in the context of the MRC asymptomatic carotid surgery trial (ACST), as the numbers suitable for CEA will probably increase further in the future.

Cost-effectiveness of endarterectomy in patients with asymptomatic carotid artery stenosis

Long-term health outcomes and costs are important when deciding whether a strategy of carotid endarterectomy in addition to best medical management should be recommended for patients with asymptomatic carotid artery stenosis. This study investigated the cost-effectiveness of such a strategy compared with a strategy of best medical management alone. Based on data from the randomized Asymptomatic Carotid Surgery Trial (ACST), a national vascular database and other published sources, expected costs and health outcomes in terms of quality-adjusted life years (QALYs) of both treatment strategies were estimated using decision-analytical modelling. Cost-effectiveness was established for a Swedish setting from a societal perspective. Base-case analysis showed that the incremental cost per QALY of a strategy with carotid endarterectomy for 65- and 75-year-old men (women) was 34,557 euros (311,133 euros) and 58,930 euros (779,776 euros) respectively. Sensitivity analyses indicated that the duration of the treatment effect after 5 years of follow-up in the ACST was important for the cost-effectiveness results. Carotid endarterectomy in addition to best medical management can be considered cost-effective in men aged 73 years or less but is less likely to be cost-effective in older men or in women.

Carotid artery stenting: to be or not to be?

Carotid endarterectomy (CEA) has been the standard of care for suitable patients with symptomatic or asymptomatic high grade carotid stenosis since the landmark NASCET (North American Symptomatic Carotid Endarterectomy Trial), ECST (European Carotid Surgery Trial) and ACAS (Asymptomatic Carotid Artery Surgery) studies performed in the 1990s and more recently the ACST (Asymptomatic Carotid Surgery Trial). Carotid artery stenting (CAS) in the treatment of both symptomatic and asymptomatic patients with high grade carotid stenosis has recently been investigated as an alternative to CEA. We present a review of the most recent CAS trials and examine some of the controversies that surround them.

Surgery Insight: carotid endarterectomy—which patients to treat and when?

Over the past 15 years, we have witnessed a resurgence of surgery for prevention of ischemic stroke. Landmark trials including the North American Symptomatic Carotid Endarterectomy Trial and the European Carotid Surgery Trial have explored the role of carotid endarterectomy in this context, comparing the procedure with best medical treatment in patients with high-grade stenosis of the internal carotid artery and transient ischemic attack or minor nondisabling stroke in the same territory. Here, we discuss the lessons learnt from these trials, and review the Asymptomatic Carotid Atherosclerosis Study and the Asymptomatic Carotid Surgery Trial, which attempted to resolve the rather vexing issue of surgical treatment for patients with asymptomatic internal carotid artery stenosis. We also review the best medical treatment for patients undergoing carotid endarterectomy in the perioperative period, and examine the risk of ischemic stroke after CABG surgery, both when this procedure is performed alongside endarterectomy and when CABG surgery and endarterectomy are performed as a two-staged procedure.

The Argument to Support Broader Application of Extracranial Carotid Artery Stent Technology

As new technology becomes available, the stent technique for the extracranial carotid artery continues to evolve into a safer, more effective therapy for stroke prevention. With the availability of embolic protection, improved stent designs, and added endovascular physician experience, outcomes for carotid artery stenting (CAS) now consistently parallel those for carotid endarterectomy (CEA). Although carotid endarterectomy was established as the gold standard for carotid revascularization, the available scientific evidence must continue to be interpreted in the context of further advancements in nearly all related areas of medicine. One multicenter randomized trial and several nonrandomized registries have successfully established the CAS indications for patients with high surgical risk and have provided evidence to support the use of CAS techniques in patients with low surgical risk. Clinicians must continue to improve their understanding of patient-specific factors and conduct research that will refine indications while optimizing current medical therapy and that will integrate CAS and carotid endarterectomy as complementary treatments. Response by LoGerfo p 1610 The outcomes for CAS have been improving over the past 10 years and now appear nearly equivalent to those for CEA. In fact, many historical similarities are seen in the development of these 2 techniques. Although CEA was established as the gold standard for extracranial carotid revascularization, the available scientific evidence must continue to be interpreted in the context of further advancements in nearly all related areas of medicine. The current research comparing CAS and CEA has not shown a clinically robust and statistically significant difference between the 2 treatments. When differences do exist, clinicians must continue to refine patient-specific indications and to conduct further research to understand these complex risk-benefit analyses in the context of advanced medical treatments and complementary revascularization techniques. The following review details the argument to support implementation of CAS technology for athero-occlusive carotid …

Invited commentary

How many of you consider gender when deciding whether carotid endarterectomy (CEA) might be appropriate in patients with asymptomatic carotid disease? Chances are, relatively few! Yet, the Asymptomatic Carotid Atherosclerosis Study (ACAS) showed no conclusive evidence that surgery conferred benefit in women, and once perioperative strokes were included, neither did the Asymptomatic Carotid Surgery Trial (ACST). When the data from the two trials are combined, the gender differences are difficult to ignore.1Rothwell P.M. ACST: Which subgroups will benefit most from carotid endarterectomy?.Lancet. 2004; 364: 1122-1123Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar Two observations from the trials might explain why women gained less benefit. First, women had a lower natural history of stroke risk than men. Second, women incurred higher morbidity and mortality after CEA, a phenomenon common to many cardiovascular operations. Accordingly, the overall benefit from CEA will be diminished. So should all asymptomatic women now be denied surgery? Definitely not! It is, however, becoming untenable to simply treat all asymptomatic men and women as if they derived equivalent benefit. Combined ACAS and ACST data1Rothwell P.M. ACST: Which subgroups will benefit most from carotid endarterectomy?.Lancet. 2004; 364: 1122-1123Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar indicate that CEA conferred a twofold reduction in stroke in men (odds ratio, 2.0; 95% confidence interval, 1.5 to 2.8) compared with neutral benefit in women (OR 1.04; 95% confidence interval, 0.7 to 1.6). However, because the confidence intervals straddle “1,” there is still a degree of statistical uncertainty. It is inevitable, therefore, that certain women will gain considerable benefit from surgery, but can they be identified? Hellings et al have reported one of the first studies to correlate plaque biology with symptom status and gender. They hypothesize that thromboembolic stroke may be less likely to occur in women because their plaques exhibit features that are less likely to predispose them to acute plaque disruption, including reduced fat, less macrophage activity, more smooth muscle cells, higher collagen, and reduced interleukin-8 and matrix metalloproteinase-8 expression, with “asymptomatic women demonstrating the highest prevalence of stable plaques.” These are important observations, despite the unexpected finding that surface thrombus was unrelated to gender, but do their data support the statement that “selecting patients for CEA based on plaque characteristics may hold promise for the future?” Readers of the Journal of Vascular Surgery will have heard this Holy Grail being quoted many times during the last 20 years! The fundamental problem remains that no one has successfully translated postoperative histologic/biochemical features into preoperative plasma markers or ultrasound/magnetic resonance imaging parameters that can then reliably and accurately identify the high-risk patient sitting in the outpatient clinic. This is largely because few unbiased asymptomatic cohorts are now available for testing the Helling and colleagues’ hypothesis. There is, however, a potential solution. There are plans to undertake randomized trials comparing CEA with angioplasty. One, the Transatlantic Asymptomatic Carotid Intervention Trial (TACIT), intends to include “best medical therapy” as a third limb, largely because many believe pharmacotherapy to have advanced considerably since ACAS and ACST were recruiting. Patients randomized in this trial could undergo preoperative assessment of plasma markers and ultrasound/magnetic resonance imaging so that the Helling and colleagues’ hypothesis can be tested. Surgical patients would provide samples for histologic and biochemical analysis, whilst medically treated patients would provide valuable natural history data. This could be the last chance to determine optimal patient selection on the basis of evidence rather than dogma. Gender-associated differences in plaque phenotype of patients undergoing carotid endarterectomyJournal of Vascular SurgeryVol. 45Issue 2PreviewCarotid endarterectomy to prevent a stroke is less beneficial for women compared with men. This benefit is lower in asymptomatic women compared with asymptomatic men or symptomatic patients. A possible explanation for this gender-associated difference in outcome could be found in the atherosclerotic carotid plaque phenotype. We hypothesize that women, especially asymptomatic women, have more stable plaques than men, resulting in a decreased benefit of surgical plaque removal. Full-Text PDF Open Archive

Carotid endarterectomy for asymptomatic carotid stenosis

Carotid endarterectomy (CEA) is of proven benefit in recently-symptomatic patients with severe carotid stenosis. Its role in asymptomatic stenosis is still debated. The Asymptomatic Carotid Surgery Trial (ACST) more than doubled the number of patients randomised to CEA trials. This revised review incorporates the recently published ACST results. Our objective was to determine the effects of CEA for patients with asymptomatic carotid stenosis. We searched the Cochrane Stroke Group Trials Register (searched May 2004), MEDLINE (1966 to May 2004), EMBASE (1980 to June 2004), Current Contents (1995 to January 1997), and reference lists of relevant articles. We contacted researchers in the field to identify additional published and unpublished studies. All completed randomised trials comparing CEA to medical treatment in patients with asymptomatic carotid stenosis. Two reviewers extracted data and assessed trial quality. Attempts were made to contact investigators to obtain missing information. Three trials with a total of 5223 patients were included. In these trials, the overall net excess of operation-related perioperative stroke or death was 2.9%. For the primary outcome of perioperative stroke or death or any subsequent stroke, patients undergoing CEA fared better than those treated medically (relative risk (RR) 0.69, 95% confidence interval (CI) 0.57 to 0.83). Similarly, for the outcome of perioperative stroke or death or subsequent ipsilateral stroke, there was benefit for the surgical group (RR 0.71, 95% CI 0.55 to 0.90). For the outcome of any stroke or death, there was a non-significant trend towards fewer events in the surgical group (RR 0.92, 95% CI 0.83 to 1.02). Subgroup analyses were performed for the outcome of perioperative stroke or death or subsequent carotid stroke. CEA appeared more beneficial in men than in women and more beneficial in younger patients than in older patients although the data for age effect were inconclusive. There was no statistically significant difference between the treatment effect estimates in patients with different grades of stenosis but the data were insufficient. Despite about a 3% perioperative stroke or death rate, CEA for asymptomatic carotid stenosis reduces the risk of ipsilateral stroke, and any stroke, by approximately 30% over three years. However, the absolute risk reduction is small (approximately 1% per annum over the first few years of follow up in the two largest and most recent trials) but it could be higher with longer follow up.

Invited commentary

Invited commentary

Current treatments in neurology: Stroke

There have been major advances in stroke treatment based on robust evidence from large clinical trials. This review covers both acute treatment and secondary prevention. Thrombolysis is now established as a therapy for ischaemic stroke presenting within 3 hours, and the possibility of extending the time window and refining the selection of suitable patients, is being addressed in further trials. Anticoagulants are of proven benefit in cardioembolic stroke, and particularly atrial fibrillation. For prevention of other stroke subtypes antiplatelet agents appear to have a better risk-benefit ratio. Evidence for the use of dual antiplatelet therapy, including the recent MATCH study, are discussed. Carotid endarterectomy is of proven benefit in patients with>70% symptomatic stenosis. Recent analysis has emphasised the importance of operating as soon after symptom onset as possible. Operating on asymptomatic carotid stenosis remains controversial; even after the recent Asymptomatic Carotid Surgery Trial which showed that by operating on 32 people one disabling stroke or death could be prevented over a 5 years period.

Emerging Therapies for Cerebrovascular Disorders

Emerging Therapies for Cerebrovascular Disorders

Invited commentary

This is one of the largest single-center series documenting early and long-term outcomes after carotid angioplasty (CAS) in a selected group of patients deemed “high-risk” for carotid endarterectomy (CEA). In particular, it is one of few published series with 10-year follow-up data. Although it is inevitable that surgeons will disagree with some of the criteria deemed to render patients at higher risk for procedural stroke (asymptomatic atherosclerotic stenosis, asymptomatic post-CEA restenosis, and asymptomatic postradiation stenosis), the title of this paper (conveniently) shifts debate away from patient selection to focus attention on late results. This is a perfectly reasonable aim, bearing in mind the skepticism of many surgeons regarding claims that the late results of CAS are at least equivalent to CEA. In this respect, the data from this paper clearly suggest that the risk of long-term stroke after CAS is remarkably low (10-year freedom from any stroke and ipsilateral stroke was 96% and 98%). These results are much better than most contemporary surgical series and represent an improvement on parallel data from the European Carotid Surgery Trial (ECST), the North American Symptomatic Carotid Endarterectomy Trial (NASCET), the Asymptomatic Carotid Atherosclerosis Study (ACAS) and the Asymptomatic Carotid Surgery Trial (ACST). None of the randomized trials came close to reporting an annual ipsilateral stroke risk of 0.2%, although Bergeron et al do cite other studies with results similar to theirs. Interestingly, the authors have not referenced the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS).1CAVATAS InvestigatorsEndovascular versus surgical treatment in patients with carotid stenosis in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVITAS) A randomised trial.Lancet. 2001; 357: 1729-1737Abstract Full Text Full Text PDF PubMed Scopus (1363) Google Scholar Although criticized for its high procedural risk, the “much maligned” CAVATAS trial is one of the few randomized studies to have shown that following successful CAS, there is no significant difference in the risk of late stroke when compared with CEA. Notwithstanding the low risk of late stroke, which is actually the most important end-point to consider, surgeons have also been critical of apparently higher rates of restenosis after CAS compared with CEA, citing this as a major limitation for the future. Once again, the data from Bergeron would seem to suggest that this concern is unfounded. In their study, cumulative freedom from restenosis >50% was 1.8%, 3.2%, and 6.8% at 1, 2 and 10 years, respectively—again, much lower than most contemporary surgical series. In CAVATAS, CAS patients incurred a 14% risk of restenosis >70% at 1 year compared with 6.7% in CEA patients. Quite why this difference should be so marked is unknown, but merits further study. This paper has not settled issues regarding patient selection and generalizability (key unresolved issues), but it does contribute towards an increasing body of evidence that long-term outcomes are probably no different to CEA. Long-term results of carotid stenting are competitive with surgeryJournal of Vascular SurgeryVol. 41Issue 2PreviewThe feasibility of carotid stenting (CS) is no longer questionable, although its indications remain debatable. Until the results of randomized trials are available, personal series and registries should help in the comparison of long-term results of CS with those of endarterectomy. We report here the long-term results of a large series of CS in our department with a long follow-up. This retrospective study reviews a single surgeon’s 11-year experience with CS. Our results are compared with those of conventional surgery emanating from our own series and the North American Symptomatic Carotid Endarterectomy Trial (NASCET), European Carotid Surgery Trial (ECST), and Asymptomatic Carotid Atherosclerosis Study (ACAS). Full-Text PDF Open Archive

Major Ongoing Stroke Trials

Major Ongoing Stroke Trials

Prevention and Health Services Delivery

The burden of stroke to the health care system in the United States continues to increase. Stroke-related hospital admissions grew from 580 000 in 1988 to 820 000 in 1997, an 18.6% increase after age adjustment.1 More effective stroke prevention provides the primary means of reducing these alarming statistics. This can be accomplished through better implementation of known preventive strategies2 and through research into new approaches to stroke prevention. Diet can affect stroke risk, with epidemiological studies indicating an inverse relationship between fruit and vegetable consumption and cardiovascular events.2 For example, one study including individuals free of cardiovascular disease at baseline found that the relative risk (RR) of stroke was reduced by 31% (RR, 0.69; 95% CI, 0.52 to 0.92) for persons in the highest quintile of fruit and vegetable intake.3 Analysis of data from the National Health and Nutrition Examination Survey (NHANES) Epidemiologic Follow-up Study supports these results.4 The study included 9608 adults aged 25 to 74 years who were free of cardiovascular disease at a baseline evaluation between 1971 and 1975. Consumption of fruits and vegetables ≥3 times per day compared with <1 time per day was associated with a 27% lower stroke incidence (RR, 0.73; 95% CI, 0.57 to 0.95) after adjustment for potential confounders, suggesting the benefit is not attributable to a healthy-user effect. The results reinforce present recommendations for an intake of 5 servings of fruits and vegetables daily. Because fruits and vegetables contain antioxidants, antioxidant food supplements might be expected to have similar benefits. However, a 3-year study of patients with coronary heart disease, low levels of high-density lipoprotein cholesterol, and normal levels of low-density lipoprotein cholesterol found no reduction in cardiovascular end points (death, myocardial infarction, stroke, and revascularization procedures) with the use of antioxidant supplements (800 IU …

Should people with asymptomatic carotid artery stenosis undergo endarterectomy for primary stroke prevention?

Halliday A, Mansfield A, Marro J, Peto C, Peto R, Potter J, et al; MRC Asymptomatic Carotid Surgery Trial (ACST) Collaborative Group. Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial. Lancet

Does the Modern Concept of ‘Best Medical Therapy’ Render Carotid Surgery Obsolete?

Few operations have aroused such intense scientific scrutiny as carotid endarterectomy (CEA). Despite the provision of level I (Grade A) evidence supporting the role of CEA in symptomatic and asymptomatic patients, its role still generates widely conflicting opinions around the globe. The latest controversies relate to; (i) recent improvements in the concept of ‘best medical therapy’, (ii) continued scepticism about the overall generalisability of the operative risks reported in the international trials and (iii) the emergence of angioplasty as an alternative to surgery. This article will focus on an increasingly popular viewpoint (especially among stroke physicians) that improvements in best medical therapy (BMT) now render carotid surgery (and thus by implication, angioplasty) obsolete. While the European Carotid Surgery Trial (ECST), the North American Symptomatic Carotid Endarterectomy trial (NASCET), the Asymptomatic Carotid Atherosclerosis Study (ACAS) and the Asymptomatic Carotid Surgery Trial (ACST) were recruiting, the concept of BMT was relatively primitive. To many clinicians it simply meant stopping smoking, starting aspirin and treating hypertension/angina ‘as best possible’. Few were prescribed lipid-lowering drugs and many hypertensive patients simply did not achieve satisfactory control of blood pressure. Moreover, the responsibility for ensuring implementation of BMT was often delegated to a junior member of the team. So what has changed? Improvements in what currently constitutes ‘modern’ BMT can be summarised as; (i) alternative (dual) antiplatelet therapy, (ii)

Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomized controlled trial: MRC Asymptomatic Carotid Surgery Trial (ACST) collaborative group. Lancet 2004;363:1491–1502

Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomized controlled trial: MRC Asymptomatic Carotid Surgery Trial (ACST) collaborative group. Lancet 2004;363:1491–1502

Major Ongoing Stroke Trials

Major Ongoing Stroke Trials