Gowri Raman, MD, MS; Denish Moorthy, MBBS, MS; Nira Hadar, MS; Issa J. Dahabreh, MD, MS; Thomas F. O'Donnell, MD; David E. Thaler, MD, PhD; Edward Feldmann, MD; Joseph Lau, MD; Georgios D. Kitsios, MD, PhD
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Requests for Single Reprints: Gowri Raman, MD, MS, Tufts Center for Clinical Evidence Synthesis, Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Box 63, 800 Washington Street, Boston, MA 02111; e-mail, email@example.com.
Current Author Addresses: Drs. Raman and Moorthy: Tufts Center for Clinical Evidence Synthesis, Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Box 63, 800 Washington Street, Boston, MA 02111.
Ms. Hadar and Drs. Dahabreh and Lau: Center for Evidence-based Medicine, Box G-S121-8, 121 South Main Street, Brown University, Providence, RI 02912.
Dr. O'Donnell: Department of Vascular Surgery, Tufts Medical Center, Box 259, 800 Washington Street, Boston, MA 02111.
Drs. Thaler and Feldman: Department of Neurology, Tufts Medical Center, Box 314, 800 Washington Street, Boston, MA 02111.
Dr. Kitsios: Department of Internal Medicine, Lahey Hospital and Medical Center, 41 Mall Road, Burlington, MA 01805.
Author Contributions: Conception and design: G. Raman, D. Moorthy, N. Hadar, G.D. Kitsios.
Analysis and interpretation of the data: G. Raman, D. Moorthy, N. Hadar, I.J. Dahabreh, T.F. O'Donnell, D.E. Thaler, E. Feldmann, G.D. Kitsios.
Drafting of the article: G. Raman, D. Moorthy, N. Hadar, E. Feldmann, G.D. Kitsios.
Critical revision of the article for important intellectual content: G. Raman, D. Moorthy, I.J. Dahabreh, T.F. O'Donnell, D.E. Thaler, E. Feldmann, J. Lau, G.D. Kitsios.
Final approval of the article: G. Raman, D. Moorthy, N. Hadar, I.J. Dahabreh, T.F. O'Donnell, D.E. Thaler, E. Feldmann, J. Lau, G.D. Kitsios.
Provision of study materials or patients: G. Raman, G.D. Kitsios.
Statistical expertise: G. Raman, D. Moorthy, I.J. Dahabreh, G.D. Kitsios.
Obtaining of funding: J. Lau.
Administrative, technical, or logistic support: G. Raman, D. Moorthy, J. Lau, G.D. Kitsios.
Collection and assembly of data: G. Raman, D. Moorthy, N. Hadar, D.E. Thaler, G.D. Kitsios.
Adults with asymptomatic carotid artery stenosis are at increased risk for ipsilateral carotid territory ischemic stroke.
To examine comparative evidence on management strategies for asymptomatic carotid stenosis and the incidence of ipsilateral stroke with medical therapy alone.
MEDLINE, Cochrane Central Register of Controlled Trials, U.S. Food and Drug Administration documents, and review of references through 31 December 2012.
Randomized, controlled trials (RCTs) and prospective or retrospective nonrandomized, comparative studies of medical therapy alone, carotid endarterectomy (CEA) plus medical therapy, or carotid artery stenting (CAS) plus medical therapy for adults with asymptomatic carotid stenosis, as well as single-group prospective cohort studies of medical therapy, were reviewed.
Two investigators extracted information on study and population characteristics, results, and risk of bias.
Forty-seven studies in 56 publications were eligible. The RCTs comparing CAS and CEA were clinically heterogeneous; 1 RCT reported more but not statistically significant ipsilateral stroke events (including any periprocedural stroke) in CAS compared with CEA, whereas another RCT, in a population at high surgical risk for CEA, did not. Three RCTs showed that CEA reduced the risk for ipsilateral stroke (including any periprocedural stroke) compared with medical therapy alone, but these results may no longer be applicable to contemporary clinical practice. No RCT compared CAS versus medical therapy alone. The summary incidence of ipsilateral stroke across 26 cohorts receiving medical therapy alone was 1.68% per year.
Studies defined asymptomatic status heterogeneously. Participants in RCTs did not receive best-available medical therapy.
Future RCTs of asymptomatic carotid artery stenosis should explore whether revascularization interventions provide benefit to patients treated by best-available medical therapy.
Agency for Healthcare Research and Quality.
Summary of evidence search and selection.
CAS = carotid artery stenting; CEA = carotid endarterectomy; CENTRAL = Central Register of Controlled Trials; NRCS = nonrandomized, comparative study; RCT = randomized, controlled trial.
* Indicates overlap of studies.
Table 1. Summary Characteristics of RCTs Comparing Treatment Strategies in Asymptomatic Carotid Stenosis
Table 2. Summary Assessment of Strength of Evidence for Comparisons Among Interventions
Appendix Table 1. Results Comparing CAS Plus Medical Therapy With CEA Plus Medical Therapy for Asymptomatic Carotid Stenosis
Forest plot of ipsilateral stroke (including any stroke within 30 days) in RCTs of CAS versus CEA.
CAS = carotid artery stenting; CEA = carotid endarterectomy; CREST = Carotid Revascularization Endarterectomy Versus Stenting Trial; RCT = randomized, controlled trial; SAPPHIRE = Stenting and Angioplasty With Protection in Patients at High Risk for Endarterectomy.
Appendix Table 2. Results Comparing CEA Plus Medical Therapy With Medical Therapy Alone in Asymptomatic Carotid Stenosis
Meta-analysis of ipsilateral stroke (including any stroke within 30 days) in RCTs and NRCSs of CEA versus medical therapy.
ACAS = Asymptomatic Carotid Atherosclerosis Study; ACST = Asymptomatic Carotid Surgery Trial; CEA = carotid endarterectomy; NRCS = nonrandomized, comparative study; RCT = randomized, controlled trial; VA = Veterans Affairs.
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Simone Vidale, Silvio Bellocchi*, Roberto Caronno°
Department of Neurology & Stroke Unit, *Department of Neurosurgery, °Department of Vascular Surgery - Sant'Anna Hospital - Como, Italy
May 27, 2013
Asymptomatic carotid stenosis: to treat or not to treat. The never ending dilemma
We read with interest the systematic review concerning the management of asymptomatic carotid stenosis by Raman G et al.1 They concluded that a superiority of endarterectomy (CEA) or stenting (CAS) could not be reached, while the stroke risk is lower in CEA plus medical therapy groups than in those with medical therapy alone. As reported by Authors, one of the principal limitation of previous RCTs was the heterogeneity of patient enrolment, including different cut-off levels of carotid stenosis.
Another point to consider in these studies is the definition of asymptomatic carotid stenosis. In the last years new concepts are emerging about this argument and cognitive impairment assumed an increased importance, also related to carotid artery disease.2 Thus, a vascular cognitive decline could be a symptom of this pathological condition. Conversely an ischemic stroke attributable to carotid disease could not be confirmed at neuroimaging examinations (i.e. lacunar stroke using MRI). In each patient different vascular risk factors contribute to increase the risk of cerebrovascular events and to advance of carotid stenosis at the same time. The Framingham Study contributed to identify a stroke risk profile for each subject, considering classical vascular risk factors (i.e. hypertension, diabetes, dyslipidaemia…).3
Therefore it is reasonable the application of a personalized preventive best-available medical therapy in patients with asymptomatic carotid stenosis. Today the risk of stroke in these subjects is lower than it was in the past (i.e. during ACAS and ACST trials), by the administration of current intensive medical therapy. Now it is crucial to identify high-risk patients who could best benefit from an interventional approach. This evaluation should consider: 1. the global risk of patient with all vascular risk factors; 2. the carotid plaque vulnerability, considering its morphological characteristics;4 3. a comprehensive functional assessment, based on patient’s age, congnitive profile and daily living performances. All the limitations of previous studies could be solved by a randomized controlled trial that compares CEA, CAS and best intensive medical therapy in patients with well-defined (clinically and radiologically) asymptomatic carotid stenosis. Only in this way we will be able to apply the best clinical and cost effectiveness treatment for each patients with asymptomatic carotid stenosis.
1. Raman G, Moorthy D, Hadar N, Dahabreh IJ, O’Donnell TF, Thaler DE, Feldmann EF, Lau J, Kitsios GD. Management strategies for asymptomatic carotid stenosis. A systematic review and meta-analysis. Ann Intern Med 2013; 158: 676 – 685.
2. Johnston SC, O’Meara ES, Manolio TA, Lefkowitz D, O’Leary DH, Goldstein S, Carlson MC, Fried LP, Longstreth WT. Cognitive impairment and decline are associated with carotid artery disease in patients without clinically evident cerebrovascular disease. Ann Intern Med 2004; 140: 237 – 247.
3. Wolf PA, D’Agostino RB, Belanger AJ, Kannel WB. Probability of Stroke: a risk profile from the Framingham Study. Stroke 1991; 22: 312 – 318.4. Bogiatzi C, Cocker MS, Beanlands R, Spence JD. Identifying high-risk asymptomatic carotid stenosis. Expert Opin Med Diagnostics 2012; 6 : 139 – 151.
Raman G, Moorthy D, Hadar N, Dahabreh IJ, O'Donnell TF, Thaler DE, et al. Management Strategies for Asymptomatic Carotid Stenosis: A Systematic Review and Meta-analysis. Ann Intern Med. ;158:676–685. doi: 10.7326/0003-4819-158-9-201305070-00007
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Published: Ann Intern Med. 2013;158(9):676-685.
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