Am Fam Physician. 2008;77(7):1006-1010
This statement summarizes the U.S. Preventive Services Task Force (USPSTF) recommendations on screening for carotid artery stenosis and the supporting scientific evidence, and updates the 1996 recommendations contained in the Guide to Clinical Preventive Services, 2nd ed.1 See Table 1 for a description of the USPSTF grades and Table 2 for a description of USPSTF classification of levels of certainty regarding net benefit. The complete information on which this statement is based, including evidence tables and references, is included in the evidence synthesis2 on this topic, available on the USPSTF Web site at: http://www.uspreventiveservicestaskforce.org. The recommendation is also posted on the Web site of the National Guideline Clearinghouse at http://www.guideline.gov.
| Grade | Grade definition | Suggestions for practice |
|---|---|---|
| A | The USPSTF recommends the service. There is high certainty that the net benefit is substantial. | Offer/provide this service. |
| B | The USPSTF recommends the service. There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial. | Offer/provide this service. |
| C | The USPSTF recommends against routinely providing the service. There may be considerations that support providing the service in an individual patient. There is moderate or high certainty that the net benefit is small. | Offer/provide this service only if there are other considerations in support of offering/providing the service in an individual patient. |
| D | The USPSTF recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits. | Discourage the use of this service. |
| I | The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the service. Evidence is lacking, of poor quality or conflicting, and the balance of benefits and harms cannot be determined. | Read “Clinical Considerations” section of USPSTF Recommendation Statement. If offered, patients should understand the uncertainty about the balance of benefits and harms. |
| Level of Certainty | Description |
|---|---|
| High | The available evidence usually includes consistent results from well-designed, well-conducted studies in representative primary care populations. These studies assess the effects of the preventive service on health outcomes. This conclusion is therefore unlikely to be strongly affected by the results of future studies |
| Moderate | The available evidence is sufficient to determine the effects of the preventive service on health outcomes, but confidence in the estimate is constrained by factors such as:
|
| As more information becomes available, the magnitude or direction of the observed effect could change, and this change may be large enough to alter the conclusion | |
| Low | The available evidence is insufficient to assess effects on health outcomes. Evidence is insufficient because of:
|
| More information may allow an estimation of effects on health outcomes |
The USPSTF makes recommendations about preventive care services for patients without recognized signs or symptoms of the target condition. It bases its recommendations on a systematic review of the evidence of the benefits and harms and an assessment of the net benefit of the service.
The USPSTF recognizes that clinical or policy decisions involve more considerations than this body of evidence alone. Physicians and policy makers should understand the evidence but individualize decision making to the specific patient or situation.
For a one-page clinical summary of this recommendation statement, see Table 3, or go to http://www.ahrq.gov/clinic/uspstf07/cas/cassum.htm.
| Population | Adult general population* |
|---|---|
| Recommendation | Do not screen with ultrasound or other screening tests |
| Grade: D | |
| Risk assessment | The major risk factors for carotid artery stenosis include: older age, male sex, hypertension, smoking, hypercholesterolemia, and heart disease |
| However, accurate, reliable risk assessment tools are not available | |
| Balance of benefits and harms | Harms outweigh benefits |
| In the general population, screening with carotid duplex ultrasound would result in more false-positive results than true-positive results. This would lead to surgeries that are not indicated or to confirmatory angiography. As the result of these procedures, some patients would suffer serious harms (death, stroke, and myocardial infarction) that outweigh the potential benefit surgical treatment may have in preventing stroke | |
| Other relevant recommendations from the USPSTF | Adults should be screened for hypertension, hyperlipidemia, and smoking. Physicians should discuss aspirin chemoprevention with patients at increased risk for cardiovascular disease |
| These recommendations and related evidence are available at http://www.uspreventiveservicestaskforce.org |
Summary of Recommendations and Evidence
The USPSTF recommends against screening for asymptomatic carotid artery stenosis in the general adult population. D recommendation.
Rationale
Importance. Good evidence indicates that although stroke is a leading cause of death and disability in the United States, a relatively small proportion of all disabling, unheralded strokes is due to carotid artery stenosis.
Detection. The most feasible screening test for severe carotid artery stenosis (i.e., 60 to 99 percent stenosis) is duplex ultrasonography. Good evidence indicates that this test has moderate sensitivity and specificity and yields many false-positive results. A positive result on duplex ultrasonography is often confirmed by digital subtraction angiography, which is more accurate but can cause serious adverse events. Noninvasive confirmatory tests, such as magnetic resonance angiography, involve some inaccuracy. Given these facts, some persons with false-positive test results may receive unnecessary invasive carotid endarterectomy.
Benefits of Detection and Early Intervention. Good evidence indicates that in selected, high-risk trial participants with asymptomatic severe carotid artery stenosis, carotid endarterectomy by selected surgeons reduces the five-year absolute incidence of all strokes or perioperative death by approximately 5 percent. These benefits would be less among asymptomatic persons in the general population. For the general population, the benefits are judged to be no greater than small.
Harms of Detection and Early Intervention. Good evidence indicates that both the testing strategy and the treatment with carotid endarterectomy can cause harms. A testing strategy that includes angiography will itself cause some strokes. A testing strategy that does not include angiography will cause some strokes by leading to carotid endarterectomy in persons who do not have severe carotid artery stenosis. In excellent centers, carotid endarterectomy is associated with a 30-day stroke or mortality rate of about 3 percent; some areas have higher rates. These harms are judged to be no less than small.
USPSTF Assessment.The USPSTF concludes that for individuals with asymptomatic carotid artery stenosis, there is moderate certainty that the benefits of screening do not outweigh the harms.
Clinical Considerations
Patient Population. This recommendation applies to adults without neurologic signs or symptoms, including a history of transient ischemic attack or stroke. If otherwise eligible, an individual who has a carotid-area transient ischemic attack should be evaluated promptly for consideration of carotid endarterectomy.
Risk Assessment. In a setting of excellent surgical care and low complication rates, screening may benefit patients who have a very high risk for stroke. It is not clear, however, how to identify persons whose risk for stroke is high enough to justify screening, yet do not also have a high risk for surgical complications. The major risk factors for carotid artery stenosis include older age, male sex, hypertension, smoking, hypercholesterolemia, and heart disease.
Screening Tests. Available screening and confirmatory tests (i.e., duplex ultrasonography, digital subtraction angiography, and magnetic resonance angiography) all have imperfect sensitivity and appreciable harms. Therefore, screening could lead to non-indicated surgeries that result in serious harms, including death, stroke, and myocardial infarction, in some patients.
Useful Resources. In other recommendations, the USPSTF notes that adults should be screened for hypertension, hyperlipidemia, and smoking. In addition, physicians should discuss aspirin chemoprevention with those who have an increased risk for cardiovascular disease. The evidence and recommendations on these conditions from the USPSTF are available on the Agency for Healthcare Research and Quality Web site at http://www.uspreventiveservicestaskforce.org.
Discussion
Burden of Disease. The contribution of severe carotid artery stenosis to the morbidity and mortality associated with stroke, or to the natural progression of asymptomatic carotid artery stenosis in the general population, is not precisely known.2,3 Based on population-based studies and the accuracy of carotid duplex ultrasonography, the estimated prevalence of severe carotid artery stenosis in the general population 65 years and older is about 1 percent. Studies have found that carotid artery stenosis is more prevalent in older adults, smokers, those with hypertension, and those with heart disease. Research has not found any risk factor or clinically useful risk-stratification tool that can reliably and accurately distinguish persons who have clinically important carotid artery stenosis from those who do not.
Scope of Review. In 1996, the USPSTF concluded that evidence was insufficient to recommend for or against screening of asymptomatic patients for carotid artery stenosis by physical examination or carotid ultrasonography. To update its recommendation, the USPSTF examined high-quality evidence on the natural history of carotid artery stenosis, systematic reviews of the accuracy of screening tests, and randomized controlled trials (RCTs) of the benefits of treatment with carotid endarterectomy. Because the magnitude of potential surgical harms is such an important consideration in the treatment of carotid artery stenosis, the USPSTF conducted a systematic review of this issue.
Accuracy of Screening Tests. Two meta-analyses provide information on the accuracy of carotid duplex ultrasonography in detecting clinically important stenosis.4,5 Recent systematic reviews of studies about the accuracy of carotid duplex ultrasonography, using digital subtraction angiography as the reference standard, estimated the sensitivity to be 86 to 90 percent and the specificity to be 87 to 94 percent for detecting carotid artery stenosis greater than 70 percent.4,5 The estimated sensitivity and specificity of carotid duplex ultrasonography to detect severe carotid artery stenosis are approximately 94 and 92 percent, respectively.4 The reliability of carotid duplex ultrasonography is not established.4 One meta-analysis noted that the measurement properties used among various ultrasonography laboratories varied greatly and to a clinically important degree.4 In 1996, the USPSTF reviewed the evidence for screening for bruits on physical examination and found that the test had poor reliability and sensitivity.1
Effectiveness of Early Detection and Treatment. Two good-quality RCTs, the Asymptomatic Carotid Atherosclerosis Study (ACAS) and the Asymptomatic Carotid Surgery Trial (ACST), compared carotid endarterectomy plus medical management to medical management alone in participants without symptoms attributable to the studied artery.6,7 The ACAS projected a five-year rate of ipsilateral stroke and any perioperative stroke or death that was lower in the carotid endarterectomy group than in the medical management group: 5.1 percent versus 11.0 percent (relative risk [RR] reduction = 0.5; 95% confidence interval [CI], 0.22 to 0.72). If strokes associated with angiography were included, the difference between the groups was 5.6 percent versus 11.0 percent, or an absolute difference of 5.4 percentage points over five years. The estimated RR reduction was greater for men than for women (0.66 and 0.17, respectively). The ACST projected a lower five-year rate of any stroke or perioperative death in the carotid endarterectomy group than in the medical management group: 6.4 percent versus 11.8 percent (absolute difference, 5.4 percentage points [95% CI, 2.96 to 7.75]). About one half of the strokes prevented by carotid endarterectomy were disabling. The treatment groups did not differ significantly in all-cause mortality in either study.
The RCTs on carotid endarterectomy for asymptomatic carotid artery stenosis have important limitations in terms of their generalizability to the primary care population. The RCTs included highly selected participants and surgeons. The 30-day perioperative results of the RCTs were reported as a combined outcome that did not include acute nonfatal myocardial infarction, which is an important complication. The medical treatment arm in the RCTs was poorly defined, was not kept constant over the course of the study, and would not have included treatments that are now considered to be optimal medical management, including aggressive management of blood pressure and lipid levels.
Potential Harms of Screening and Treatment. Tests to confirm results from carotid duplex ultrasonography have associated harms. If all positive tests are followed by digital subtraction angiography, about 1 percent of persons would experience a nonfatal stroke as a result of angiography. If positive tests are not followed by confirmatory angiography, but rather by magnetic resonance angiography or computed tomography angiography—tests with less than 100 percent accuracy—some patients will have unnecessary carotid endarterectomy, with consequent harms in the absence of proven benefit.
Fourteen good- or fair-quality observational studies that evaluated carotid endarterectomy complications in patients with asymptomatic carotid artery stenosis were identified for USPSTF review. Overall, 30-day perioperative stroke or death rates in asymptomatic patients ranged from 1.6 to 3.7 percent.3 Participants in ACAS had a 2.7 percent overall perioperative rate of stroke or death (1.7 percent for men and 3.6 percent for women). In ACST, the perioperative rate of stroke or death was 3.1 percent overall, but was higher for women (3.7 percent) than for men (2.4 percent). The observational studies reporting perioperative nonfatal myocardial infarctions showed a rate of approximately 0.7 to 1.1 percent.8–10 Patients with more comorbid conditions had a 3.3 percent rate of nonfatal myocardial infarction.9 The rate of nonfatal perioperative myocardial infarction reported for the surgical group in the RCTs varied from 0.6 to 1.9 percent. Two Medicare-based studies found variation in perioperative stroke and death among 10 states.11,12 In the first study, the statewide rates ranged from 2.3 to 6.7 percent; a follow-up study for the same 10 states found similar results as in 2001, with rates ranging from 1.4 to 6.0 percent.
Estimate of the Magnitude of Net Benefit. In patients and surgeons similar to those in the RCTs, treatment with carotid endarterectomy for asymptomatic carotid artery stenosis can result in a net absolute reduction in stroke rates—approximately 5 percent over five to six years (about 2.5 percent absolute risk reduction for disabling strokes). The number needed to treat (NNT) for five years to prevent one stroke is about 20 (NNT to prevent one disabling stroke is about 40). This benefit has been shown in selected patients with selected surgeons and must be weighed against a small increase in nonfatal myocardial infarctions. The net benefit for carotid endarterectomy largely depends on patients surviving the perioperative period without complications and living for five years. The two RCTs that found a benefit to surgery compared with medical management had 30-day perioperative rates of stroke and death of 2.7 to 3.1 percent, and some large observational studies have shown higher rates.
If ultrasonography screening were followed by magnetic resonance angiography confirmation, about 23 strokes would be prevented over five years by screening 100,000 persons with a prevalence of carotid artery stenosis of 1 percent. Thus, about 4,348 persons would need to undergo screening to prevent one stroke (number needed to screen) after five years. Twice this number (8,696) would need to be screened to prevent one disabling stroke.
How Does the Evidence Fit with Biological Understanding? The medical treatment group in the RCTs was poorly defined and probably did not include intensive blood pressure and lipid control, which is standard practice today. It is difficult to determine what effect current standard medical therapy would have on overall benefit from carotid endarterectomy. The Kaplan-Meier curves in ACST cross from net harm to net benefit at about 1.5 years after carotid endarterectomy for men and at nearly three years after carotid endarterectomy for women.13–17 The average follow-up time in ACAS and ACST was 2.7 and 3.4 years, respectively; the estimated survival beyond the actual follow-up time may not be applicable in this situation. It is possible that the benefit from carotid endarterectomy is limited to a specific interval and does not continue unabated into the future. Thus, the actual (not projected) risk reduction for carotid endarterectomy over five to 10 years is still uncertain.
Although this report did not review the evidence on medical treatment, accepted medical strategies to prevent stroke are available. Until research addresses the gaps in the evidence that screening and treatment with carotid endarterectomy provides overall benefits to the general population, physicians' efforts might be more practically focused on optimizing medical management of risk factors of stroke.
Recommendations of Others
In 2006, the American Heart Association/American Stroke Association did not recommend screening the general population for asymptomatic carotid artery stenosis.18 The American Society of Neuroimaging released recommendations in 2007 that also recommended against screening in unselected populations but advised that screening should be considered in adults 65 years and older with three or more cardiovascular risk factors.19 In 2007, the Society for Vascular Surgery recommended ultrasonography screening for persons 55 years and older with cardiovascular risk factors, such as a history of hypertension, diabetes, smoking, hypercholesterolemia, or known cardiovascular disease.20