Cathy A. Sila, M.D. Medical Management : Recommendations for the treatment of a patient with asymptomatic carotid stenosis of 70 to 80%, such as the patient in the case vignette, should be based on an understanding of the adverse events that are most likely to occur and the benefits and risks of the treatment over time. The best outcome-based data for patients with asymptomatic carotid stenosis come from the Asymptomatic Carotid Atherosclerosis Study (ACAS) and the Asymptomatic Carotid Surgery Trial (ACST; Current Controlled Trials number, ISRCTN26156392 [controlled-trials.com] ).1,2 Although stroke may be the most feared consequence of carotid disease,
the most common adverse event in these studies was death from myocardial infarction or other (nonstroke) cardiovascular causes. Nonfatal myocardial infarctions were not reported separately, but the rate of fatal events alone is consistent with a high risk of coronary heart disease according to the Framingham model (>20% over a 10-year period). Fatal or nonfatal strokes were the next-most-common adverse events, but only one third to one half of these strokes were ischemic and ipsilateral and could be attributed to the carotid stenosis. Aggressive medical management of vascular risk factors can reduce both coronary and cerebrovascular events in patients with carotid disease, although the definition and execution of medical therapy vary from trial to trial. In five randomized clinical trials (including ACAS and ACST) of medical therapy alone for asymptomatic carotid stenosis as compared with endarterectomy plus medical therapy, the medical therapy consisted of an antiplatelet regimen and counseling about risk factors, but the subsequent care of patients was delegated to the primary physician. Although the degree of compliance with antiplatelet therapy was reported, the degree of success with control of risk factors was not. In the ACST, the definition of best medical therapy evolved during the study, with patients in the final cohort receiving antiplatelet therapy (given to 90% of patients), antihypertensive therapy (81%), and lipid-lowering therapy (70%). Three of the five trials, including a total of 925 patients with asymptomatic carotid stenosis of more than 50%, showed no significant reduction in the risk of stroke or death with endarterectomy as compared with medical therapy alone. In the two larger trials, including a total of 4782 patients with asymptomatic carotid stenosis of 60 to 99% or 70 to 99%, adding endarterectomy to medical therapy did reduce the combined rate of ipsilateral stroke at 5 years and perioperative stroke and death (11.0 to 11.8% reduced to 5.1 to 6.4%), with low procedural risk (2.3 to 3.1%). However, the goal of preventing a disabling or fatal stroke with the use of surgery was achieved only in ACST, and that reduction of 0.5% per year means that 40 patients would need to be treated to prevent one major stroke over a 5-year period. Medical therapy alone should be recommended if procedural risks (of surgery as well as angiography) are expected to exceed 3.0%. Unfortunately, in contrast to rates in the trials discussed above, rates as high as 4.7 to 6.7% have been reported with endarterectomy in other clinical trials and in the Medicare population.3 Published postapproval carotid-stenting registries have also reported procedural risks exceeding the safety threshold set by the American Heart Association and the American Academy of Neurology. Currently, carotid stenting for asymptomatic stenosis in low-risk patients is reimbursed by the Centers for Medicare and Medicaid Services only in the context of a clinical trial approved by the Food and Drug Administration (FDA). Such patients should be referred to ongoing randomized trials — the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST; ClinicalTrials.gov number, NCT00004732 [ClinicalTrials.gov] ) or the Carotid Stenting vs. Surgery of Severe Carotid Artery Disease and Stroke Prevention in Asymptomatic Patients (ACT I) trial (ClinicalTrials.gov number, NCT00106938 [ClinicalTrials.gov] ). Also, since the risks of revascularization are immediate, whereas the benefit to an asymptomatic patient is accrued only over time, high-risk asymptomatic patients with poor 5-year survival (e.g., those with previous vascular surgery, claudication, cardiac disease, an abnormal electrocardiogram, diabetes mellitus, or older age) should also be treated medically.4 Available data from the clinical trials probably underestimate the benefit that could be derived from medical intervention. For the patient in the case vignette, I would encourage lifestyle modifications including weight and girth loss, dietary counseling, and lipid-lowering therapy to achieve a low-density lipoprotein level of less than 100 mg per deciliter (2.6 mmol per liter) (with consideration of a target of <70>
the most common adverse event in these studies was death from myocardial infarction or other (nonstroke) cardiovascular causes. Nonfatal myocardial infarctions were not reported separately, but the rate of fatal events alone is consistent with a high risk of coronary heart disease according to the Framingham model (>20% over a 10-year period). Fatal or nonfatal strokes were the next-most-common adverse events, but only one third to one half of these strokes were ischemic and ipsilateral and could be attributed to the carotid stenosis. Aggressive medical management of vascular risk factors can reduce both coronary and cerebrovascular events in patients with carotid disease, although the definition and execution of medical therapy vary from trial to trial. In five randomized clinical trials (including ACAS and ACST) of medical therapy alone for asymptomatic carotid stenosis as compared with endarterectomy plus medical therapy, the medical therapy consisted of an antiplatelet regimen and counseling about risk factors, but the subsequent care of patients was delegated to the primary physician. Although the degree of compliance with antiplatelet therapy was reported, the degree of success with control of risk factors was not. In the ACST, the definition of best medical therapy evolved during the study, with patients in the final cohort receiving antiplatelet therapy (given to 90% of patients), antihypertensive therapy (81%), and lipid-lowering therapy (70%). Three of the five trials, including a total of 925 patients with asymptomatic carotid stenosis of more than 50%, showed no significant reduction in the risk of stroke or death with endarterectomy as compared with medical therapy alone. In the two larger trials, including a total of 4782 patients with asymptomatic carotid stenosis of 60 to 99% or 70 to 99%, adding endarterectomy to medical therapy did reduce the combined rate of ipsilateral stroke at 5 years and perioperative stroke and death (11.0 to 11.8% reduced to 5.1 to 6.4%), with low procedural risk (2.3 to 3.1%). However, the goal of preventing a disabling or fatal stroke with the use of surgery was achieved only in ACST, and that reduction of 0.5% per year means that 40 patients would need to be treated to prevent one major stroke over a 5-year period. Medical therapy alone should be recommended if procedural risks (of surgery as well as angiography) are expected to exceed 3.0%. Unfortunately, in contrast to rates in the trials discussed above, rates as high as 4.7 to 6.7% have been reported with endarterectomy in other clinical trials and in the Medicare population.3 Published postapproval carotid-stenting registries have also reported procedural risks exceeding the safety threshold set by the American Heart Association and the American Academy of Neurology. Currently, carotid stenting for asymptomatic stenosis in low-risk patients is reimbursed by the Centers for Medicare and Medicaid Services only in the context of a clinical trial approved by the Food and Drug Administration (FDA). Such patients should be referred to ongoing randomized trials — the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST; ClinicalTrials.gov number, NCT00004732 [ClinicalTrials.gov] ) or the Carotid Stenting vs. Surgery of Severe Carotid Artery Disease and Stroke Prevention in Asymptomatic Patients (ACT I) trial (ClinicalTrials.gov number, NCT00106938 [ClinicalTrials.gov] ). Also, since the risks of revascularization are immediate, whereas the benefit to an asymptomatic patient is accrued only over time, high-risk asymptomatic patients with poor 5-year survival (e.g., those with previous vascular surgery, claudication, cardiac disease, an abnormal electrocardiogram, diabetes mellitus, or older age) should also be treated medically.4 Available data from the clinical trials probably underestimate the benefit that could be derived from medical intervention. For the patient in the case vignette, I would encourage lifestyle modifications including weight and girth loss, dietary counseling, and lipid-lowering therapy to achieve a low-density lipoprotein level of less than 100 mg per deciliter (2.6 mmol per liter) (with consideration of a target of <70>
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