Although deaths from stroke have declined steadily over the last 50 years,1 stroke remains the fifth leading cause of death and the primary cause of neurological disability in the United States, where 610 000 first-ever strokes occur each year and more than 146 000 people die.2 Given the devastating consequences of stroke, the goal of identifying who is at high risk to initiate preventive measures remains a high priority.
A total of 34% of strokes are ischemic strokes resulting from carotid artery disease, with the remaining strokes coming from the vertebrobasilar territory, intracranial vessels, or the heart.2 However, most individuals who experience these strokes do not have a moderate or higher stenosis that could have been detected and treated in advance of the stroke; only 14% of strokes result from thromboembolism from a previously asymptomatic stenosis of the internal carotid artery.3 The remaining strokes occur in individuals with at most minor carotid narrowing who would not have been candidates for intervention. Furthermore, some of these 14% of individuals will experience a warning transient ischemic attack, leaving about 11% of individuals whose stroke is due to thromboembolism from a previously asymptomatic stenosis.3 These are the individuals with stroke who could potentially benefit from prior carotid screening. Given that only 11% of strokes are associated with previously undiagnosed carotid stenosis, the impact of ultrasonographic screening on overall stroke prevention is limited, but preventing stroke in individuals with previously undiagnosed carotid stenosis is important, particularly when effective therapies are available.
Therefore, the goal of screening patients to find those with carotid narrowing has strong face validity, even with the need to screen a large number of people to identify those with the potential to benefit. However, it is widely estimated that only a small proportion of strokes can actually be prevented, in large part owing to logistics of screening and finding individuals with stenosis amenable to treatment. The 11% of potentially preventable strokes would need be identified among individuals who have antecedent carotid narrowing. Overall, only 1% to 3% of individuals with stenosis have severe narrowing,4,5 so many individuals would have to be screened to identify the few who would potentially benefit from treatments.
The US Preventive Services Task Force (USPSTF) has published a new recommendation statement on screening asymptomatic individuals for carotid stenosis with the goal of preventing stroke.6,7 The USPSTF has used a reaffirmation process to assess whether their prior 2014 recommendation (a D recommendation against screening) should be changed based on new interval evidence.6,7 Interval studies of treatment of greater than 70% carotid stenosis continue to suggest small benefit (from carotid endarterectomy) or no benefit compared with best medical therapy (ie, carotid stenting), and both procedures are associated with meaningful short-term harms of postoperative stroke or death, estimated as occurring in 0.5% to 5.1% of patients from the methodologically diverse studies that were reviewed.6,7 No externally validated risk stratification tools were identified that could reliably distinguish between individuals who have asymptomatic but clinically important carotid artery stenosis vs individuals who do not, or that could assess the risk of stroke in an individual associated with carotid artery stenosis. All reviewed studies included patients with higher risk, making extrapolation of results to asymptomatic, typical-risk populations difficult.6,7 The USPSTF found that the interval evidence did not provide a basis to change their recommendation against screening and issued the D recommendation based on evidence that the harms of screening for carotid artery stenosis in adults who are asymptomatic outweigh the benefits.6,7
The crux of the USPSTF rationale in this recommendation (as in prior recommendations on this topic) hinges on the harms of treatment,6,7 an important consideration given the large number of people who would have to be screened to identify a relatively small group of individuals with stenosis and the inevitable potential for some rate of overdiagnosis (ie, stenosis that is unlikely to cause future stroke) leading to overtreatment. While the D grade is not surprising given this consideration, what continues to be striking is the overall absence of direct evidence that screening itself is actually beneficial.6,7
Without a true randomized clinical trial to directly answer the question, there is a lack of consensus and clarity on the role of carotid ultrasonographic screening for prevention of stroke in individuals who are asymptomatic in clinical practice. Nearly all of the specialty societies actually agree with the USPSTF and recommend against screening with carotid ultrasonography.6-11 However, these strong statements against screenings are all followed by the list of exceptions of individuals who, based on risk factors or other characteristics, should in fact be screened. The risk factors for stroke, such as high blood pressure, hyperlipidemia, diabetes, and lifestyle factors, including smoking, limited physical activity, and poor diet, are present in nearly one-third of US adults, and there are no validated combinations of these risk factors to identify individuals who might benefit from screening.
It is worth noting that individuals who are asymptomatic actually are being screened in high numbers. An estimated 1.3 to 1.6 million asymptomatic individuals undergo screening for carotid artery stenosis every year.12 Data from 2009 Medicare claims7 found that screening for asymptomatic carotid artery stenosis occurred in 6.6% of Medicare beneficiaries, a similar prevalence to that observed in a study of integrated health systems in 2016.4 An analysis of patients ages 65 years and older undergoing carotid revascularization for asymptomatic carotid stenosis between 2005 and 2009 in the Veterans Health Administration found that the rates of imaging deemed appropriate based on expert opinion was only 5.4%.7 The most common indications listed for carotid imaging in individuals who are asymptomatic was carotid bruit, an examination finding recognized in previous USPSTF reviews as having limited value for identifying stenosis. The second most common indication was previously documented carotid stenosis, a reminder that an often hidden harm of the initial screening is the multiple cascade of images that are then produced.
The only way to know if screening is beneficial would be to conduct a randomized clinical trial in which individuals who are asymptomatic or patients with cardiovascular risk factors, such as hypertension or smoking, are randomized to undergo screening or not, and then to follow the patients over the course of 3 to 5 (preferably even 10) years to see if patients who were screened had improved or worsened outcomes. Since there are very well-characterized and expected immediate complications after the interventional treatments of endarterectomy and stenting, any trial would have to be long enough for patients to accrue the potential benefit of reduced strokes, since the immediate 30-day outcomes would always be worse in these intervention groups. The trial of diagnostic ultrasonography would be judged on the basis of clinically meaningful outcomes (eg, death, stroke, and other cardiovascular outcomes, such as myocardial infraction), which would be driven by benefits and harms of the medical and surgical treatments that result from the ultrasonographic screening. Since there remains uncertainty regarding the best treatment approach for patients identified with carotid narrowing, patients could be further randomized to the treatment if identified with significant carotid narrowing, including best medical therapy (ie, statins, antiplatelets, antihypertensives, and lifestyle modifications), revascularization techniques, and combinations of both. Such a trial would not be judged by the outcome of whether the patient was helped or harmed by the screening itself; the description of ultrasonography as a safe and harmless test, which is the usual rationale noted when finding exceptions to the injunction against screening, is disingenuous unless the downstream interventions and outcomes are taken into consideration.
Is a trial worth it? Without it, the USPSTF6,7 and other guideline-making organizations will be continually considering evidence of new surgical treatments that will have varying benefit-to-harm ratios, and these will be judged against also improving general medical therapies that would be recommended regardless of the screening. None of these studies of treatments would address the larger issue of whether to screen with carotid ultrasonography and who is most likely to benefit. Randomized clinical trials of medical imaging that randomize participants to receive imaging or not have been performed for a range of conditions for which the follow-up assessed meaningful clinical outcomes.13-16 A randomized clinical trial should be conducted for imaging to detect carotid artery stenosis with the goal of preventing stroke. Imaging for screening should be put through the same rigorous evaluation as medical treatments and surgical interventions, particularly when the imaging directly results in the use of such treatments and medications. In the absence of meaningful data, patients should not be screened or followed with surveillance ultrasonography unless they are symptomatic with a transient ischemic attack or another suspicious neurological finding. This new review by the USPSTF6,7 does not add new information. But perhaps it does give us a renewed opportunity to allow the science to guide us on the potential benefits and harms of screening.
Published: February 2, 2021. doi:10.1001/jamanetworkopen.2020.36218
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Smith-Bindman R et al. JAMA Network Open.
Corresponding Author: Kirsten Bibbins-Domingo, PhD, MD, MAS, Department of Epidemiology and Biostatistics, University of California, San Francisco, 550 16th St, San Francisco, CA 94158 (email@example.com).
Conflict of Interest Disclosures: Dr Bibbins-Domingo reported serving as a member of the USPSTF from 2010 to 2017 and an author of the 2014 USPSTF recommendation.
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Smith-Bindman R, Bibbins-Domingo K. USPSTF Recommendations for Screening for Carotid Stenosis to Prevent Stroke—The Need for More Data. JAMA Netw Open. 2021;4(2):e2036218. doi:10.1001/jamanetworkopen.2020.36218
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