Daniel E. Jonas, MD, MPH; Cynthia Feltner, MD, MPH; Halle R. Amick, MSPH; Stacey Sheridan, MD, MPH; Zhi-Jie Zheng, MD, MPH, PhD; Daniel J. Watford, MD, MPH; Jamie L. Carter, MD, MPH; Cassandra J. Rowe, MPH; Russell Harris, MD, MPH
Disclaimer: The views expressed in this article do not represent and should not be construed to represent a determination or policy of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
Acknowledgment: The authors thank the following persons for their support, commitment, and contributions to this project: Tracy Wolff, MD, MPH, Agency for Healthcare Research and Quality Medical Officer; Kirsten Bibbins-Domingo, PhD, MD, Jessica Herzstein, MD, MPH, and Michael LeFevre, MD, MSPH, U.S. Preventive Services Task Force leads; Evelyn Whitlock, MD, MPH, Kaiser Permanente Research Affiliates Evidence-based Practice Center Director; Tracy Beil, MS, Kaiser Permanente Research Affiliates Evidence-based Practice Center; Carol Woodell, BSPH, Research Triangle Institute–University of North Carolina Evidence-based Practice Center Project Manager; Meera Viswanathan, PhD, Research Triangle Institute–University of North Carolina Evidence-based Practice Center Director; Christiane Voisin, MSLS, Evidence-based Practice Center Librarian; Claire Baker, research assistant; Laura Small, Evidence-based Practice Center editor; and Loraine Monroe, Evidence-based Practice Center publications specialist.
Financial Support: Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services (contract HHSA290201200015iTO2).
Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M14-0530.
Requests for Single Reprints: Daniel E. Jonas, MD, MPH, Department of Medicine, University of North Carolina at Chapel Hill, 5034 Old Clinic Building, CB 7110, Chapel Hill, NC 27599; e-mail, email@example.com.
Current Author Addresses: Drs. Jonas, Feltner, and Sheridan: Department of Medicine, University of North Carolina at Chapel Hill, 5034 Old Clinic Building, CB 7110, Chapel Hill, NC 27599.
Ms. Amick, Drs. Carter and Harris, and Ms. Rowe: Cecil G. Sheps Center for Health Services Research, CB 7590, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7590.
Dr. Zheng: Research Triangle Institute International, 6110 Executive Boulevard, Suite 902, Rockville, MD 20852-3907.
Dr. Watford: Jackson Memorial Hospital, 1611 Northwest 12th Avenue, Miami, FL 33136-1096.
Author Contributions: Conception and design: D.E. Jonas, C. Feltner, H.R. Amick, S. Sheridan, Z.J. Zheng, J.L. Carter, R. Harris.
Analysis and interpretation of the data: D.E. Jonas, C. Feltner, H.R. Amick, S. Sheridan, Z.J. Zheng, D.J. Watford, J.L. Carter, R. Harris.
Drafting of the article: D.E. Jonas, C. Feltner, H.R. Amick, S. Sheridan, Z.J. Zheng, D.J. Watford.
Critical revision of the article for important intellectual content: D.E. Jonas, C. Feltner, H.R. Amick, S. Sheridan, Z.J. Zheng, D.J. Watford, J.L. Carter, R. Harris.
Final approval of the article: D.E. Jonas, C. Feltner, S. Sheridan, Z.J. Zheng, R. Harris.
Provision of study materials or patients: Z.J. Zheng.
Statistical expertise: D.E. Jonas, C. Feltner.
Obtaining of funding: D.E. Jonas.
Administrative, technical, or logistic support: D.E. Jonas, C. Feltner, H.R. Amick, Z.J. Zheng, D.J. Watford, C.J. Rowe.
Collection and assembly of data: D.E. Jonas, C. Feltner, H.R. Amick, S. Sheridan, Z.J. Zheng, D.J. Watford, J.L. Carter, C.J. Rowe.
Jonas DE, Feltner C, Amick HR, Sheridan S, Zheng Z, Watford DJ, et al. Screening for Asymptomatic Carotid Artery Stenosis: A Systematic Review and Meta-analysis for the U.S. Preventive Services Task Force. Ann Intern Med. 2014;161:336-346. doi: 10.7326/M14-0530
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Published: Ann Intern Med. 2014;161(5):336-346.
Approximately 10% of ischemic strokes are caused by carotid artery stenosis (CAS). Estimated prevalence of asymptomatic CAS is 1%.
To evaluate evidence on screening and treating asymptomatic adults for CAS.
MEDLINE, the Cochrane Library, EMBASE, and trial registries through September 2013; MEDLINE through March 2014 for trials.
Good- or fair-quality trials of screening, carotid endarterectomy (CEA), or stenting compared with medical therapy or of intensification of medical therapy; systematic reviews; multi-institution studies reporting harms; and externally validated risk-stratification tools.
Dual extraction and quality assessment.
No trials compared screening with no screening or stenting with medical therapy or assessed intensification of medical therapy, and no externally validated, reliable risk-stratification tools were found. Given the specificity of ultrasonography (range, 88% to 94% for CAS ≥50% to ≥70%), its use in low-prevalence populations would yield many false-positive results. Absolute reduction of nonperioperative strokes was 5.5% (95% CI, 3.9% to 7.0%; 3 trials; 5223 participants) over approximately 5 years for CEA compared with medical therapy. The 30-day rates of stroke or death after CEA in trials and cohort studies were 2.4% (CI, 1.7% to 3.1%; 6 trials; 3435 participants) and 3.3% (CI, 2.7% to 3.9%; 7 studies; 17 474 participants), respectively. Other harms of interventions included myocardial infarction, nerve injury, and hematoma.
Trials may have overestimated benefits and used highly selected surgeons. Medical therapy used in trials was outdated, and stroke rates have declined in recent decades. Harms may have been underreported.
Current evidence does not establish incremental overall benefit of CEA, stenting, or intensification of medical therapy. Potential for overall benefit is limited by low prevalence and harms.
Agency for Healthcare Research and Quality.
Summary of evidence search and selection.
WHO ICTRP = World Health Organization International Clinical Trials Registry Platform.
Table 1. Characteristics and Main Results of Included Fair- or Good-Quality Randomized, Controlled Trials of CEA Compared With MM for Asymptomatic CAS*
Table 2. Summary of Main Results of Meta-analyses
Meta-analyses of randomized, controlled trials comparing CEA with medical therapy, by outcome.
ACAS = Asymptomatic Carotid Atherosclerosis Study; ACST = Asymptomatic Carotid Surgery Trial; CEA = carotid endarterectomy; MM = medical management; RD = risk difference; VACS = Veterans Affairs Cooperative Study.
Rates of perioperative death or stroke after CEA, by study design.
ACAS = Asymptomatic Carotid Atherosclerosis Study; ACST = Asymptomatic Carotid Surgery Trial; CASANOVA = Carotid Artery Stenosis with Asymptomatic Narrowing: Operation Versus Aspirin; CEA = carotid endarterectomy; CREST = Carotid Revascularization Endarterectomy Versus Stenting Trial; IA = Iowa; MACE = Mayo Asymptomatic Carotid Endarterectomy; MC = Medicare; NY = New York; OH = Ohio; OK = Oklahoma; VACS = Veterans Affairs Cooperative Study.
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David L. Keller, MD
July 8, 2014
This USPSTF recommendation neglects the benefits of statins
I wish to answer to the question of what to do for an asymptomatic patient with a 70-99% ICA obstruction, discovered on a screening carotid ultrasound ordered, perhaps, by a clinician who disagrees with the USPSTF advice not to perform this screen.First, I would take a very careful history and perform as diligent a neurological examination as I can, to discern if the patient has perhaps had a small stroke with subtle signs and symptoms. Any evidence of neurological deficits consistent with stroke would change the patient's category to symptomatic, and mandate further workup.Second, if the patient is truly asymptomatic, I would classify him as having a coronary artery disease equivalent. If he is not taking a statin, I would prescribe him a strong statin (as recently defined in the 2014 AHA/ACC guidelines). If he is taking a weak statin, I would increase it to a strong statin. I would obtain consultation from a neurologist (to confirm my negative neurological exam) and discuss whether low-dose aspirin and aggressive blood pressure control are indicated. I would teach the patient extensively about the signs and symptoms of stroke, to engage him in his own care.Internists should not adhere to recommendations from the USPSTF in a blind or unquestioning fashion. The 16 primary care physicians on that committee are not responsible for the well-being of my patients. I am. The data from carotid stenosis trials which did not even look at high dose statin therapy does not apply in this new era. Atherosclerosis is a systemic disease, so it is proper to apply the findings from the heart disease studies for the benefit of our patients, pending definitive disproof of any benefit from statins for patients with carotid stenosis.
J. David Spence M.D., FRCPC, FAHA
Robarts Research Institute, Western University
September 3, 2014
The recent report of the U.S. Preventive Services Task Force on screening for carotid stenosis(1) recommended against this practice. However, carotid ultrasound is a two-edged sword.
With modern medical therapy the risk of stroke or death among patients with asymptomatic carotid stenosis is now well below the risk of carotid stenting or endarterectomy; the annual risk of ipsilateral stroke is now ~ 0.5%(2-5). Even in the most recent randomized trial comparing stenting and endarterectomy (the Carotid Revascularization Endarterectomy vs. Stenting Trial, CREST) (6), the 30-day risk of stroke or death for asymptomatic patients was 2.5% for stenting and 1.4% for endarterectomy; the 4-year risk was 4.5% with stenting and 2.7% with endarterectomy. In Medicare patients, Wang et al (7) reported that a 1-year risk of stroke or death of 16.7% for stenting and 11% for endarterectomy.
Most patients with asymptomatic carotid stenosis (~ 90) would be better off with medical therapy, and the ~ 10% at high enough risk to benefit from intervention can be identified by the presence of microemboli on transcranial Doppler(8;9).
It is therefore appropriate to recommend against screening for asymptomatic carotid stenosis if the purpose is to find victims for inappropriate intervention that is more likely to harm than help them. On the other hand, there is good reason to assess preclinical atherosclerosis to better target intensive medical therapy to high-risk patients. Most cardiovascular events occur among patients with a low risk predicted by scores such as the Framingham score(10), and measuring carotid plaque burden can significantly improve risk stratification(11-13), better than measuring carotid intima-media thickness (IMT)(14).
It is important to recognize that measurement of plaque burden (as total plaque area(15) or plaque volume, which is highly correlated with coronary calcium score(16)) is distinct from measuring IMT. IMT adds little to risk scores(17), and progression of IMT does not predict risk(18). Among patients attending a vascular prevention clinic, carotid plaque burden strongly predicted risk: after adjustment for age, sex, blood pressure, cholesterol, smoking, diabetes, homocysteine and treatment of blood pressure and cholesterol, patients with a total plaque area in the top quartile (> 119 mm2) had a nearly 40% five-year risk of stroke, death or myocardial infarction, and patients in the third quartile (47-118 mm2) had a 20% five-year risk of those events(15). Those findings were validated in a large (>6000 participants) population-based study in Norway(19;20).
Among prevention clinic patients, despite treatment according to guidelines, carotid plaque progression doubled risk after adjustment for the same risk factors listed above, and it was half the patients who had progression of plaque(15). The recognition that guideline-based therapy was failing half the patients led to a new approach, “treating arteries instead of treating risk factors”(21). This approach markedly reduced risk among patients with asymptomatic carotid stenosis: the 2-year risk of stroke dropped from 8.8% to 1%, and that of myocardial infarction from 7.6% to 1%(4). Clinical trials are now being designed to test the generalizability of that approach to other clinic populations. This cannot be done with IMT or coronary calcium, because the annual change within individuals is too small to adjust therapy in clinically meaningful time frames(22).
In summary, screening for asymptomatic carotid stenosis in order to find victims for inappropriate stenting or endarterectomy is inappropriate. Assessing preclinical atherosclerosis for the purpose of improving medical therapy is entirely appropriate.
Neurology, Prevention/Screening, Stroke.
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