Final Research Plan
Carotid Artery Stenosis: Screening, December 2007
January 23, 2014
Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
Screening for Asymptomatic Carotid Artery Stenosis
The final Research Plan is used to guide a systematic review of the evidence by researchers at an Evidence-based Practice Center. The resulting Evidence Report will form the basis of the USPSTF Recommendation Statement on this topic.
The draft Research Plan was available for comment from January 15 until February 11, 2013 at 5:00 p.m., ET.
I. Analytic Framework (Text Description)
Figure 1 is the analytic framework that depicts the eight Key Questions (KQs) to be addressed by the systematic review. The figure illustrates how screening for and treatment of asymptomatic carotid artery stenosis (CAS) (defined as 60% to 99% stenosis) could theoretically result in fewer ipsilateral strokes and deaths (KQ 1). The review will also determine whether reliable risk stratification tools are available for distinguishing among people who are at decreased, average, or increased risk of CAS (KQ 2) and for distinguishing among people with asymptomatic CAS who are at decreased, average, or increased risk of ipsilateral stroke (KQ 4). The accuracy and reliability of screening tests (with or without confirmatory tests) will be assessed in KQ 3. The benefits of treatment with carotid endarterectomy and carotid angioplasty and stenting will be addressed in KQs 5 and 6. Finally, the systematic review will address whether screening/confirmatory testing and treatment are associated with harms (KQs 7 and 8, respectively).
Abbreviations: CAS = carotid artery stenosis; CAAS = carotid angioplasty and stenting; CEA = carotid endarterectomy; KQ = key question.
1. Is there direct evidence that screening adults with duplex ultrasonography, computerized tomographic angiography (CTA), and/or magnetic resonance angiography (MRA) for asymptomatic carotid artery stenosis (CAS) reduces fatal or nonfatal ipsilateral stroke?
a. Is there direct evidence for persons at decreased risk?
b. Is there direct evidence for persons at average risk?
c. Is there direct evidence for persons at increased risk?
d. Does the evidence differ for subgroups defined by age, sex, race, or ethnicity?
2. Are externally validated, reliable risk stratification tools available that distinguish people who are more or less likely to have CAS (defined as 60% to 99% stenosis)?
3a. What are the accuracy and reliability of screening with duplex ultrasonography, used alone or followed by CTA or MRA, to detect potentially clinically important CAS (defined as 60% to 99% stenosis)?
3b. Do the accuracy and reliability differ for subgroups defined by age, sex, race, or ethnicity?
4. Are externally validated, reliable risk stratification tools available that distinguish people with asymptomatic CAS (defined as 60% to 99% stenosis) who are at decreased or increased risk of ipsilateral stroke caused by CAS?
5. For people with asymptomatic CAS (defined as 60% to 99% stenosis), does intervention with carotid endarterectomy (CEA) or carotid angioplasty and stenting (CAAS) provide incremental benefit beyond current standard medical therapy for reduction of fatal or nonfatal ipsilateral stroke?
a. Is there incremental benefit for persons at decreased risk for ipsilateral stroke caused by CAS?
b. Is there incremental benefit for persons at average risk for ipsilateral stroke caused by CAS?
c. Is there incremental benefit for persons at increased risk for ipsilateral stroke caused by CAS?
d. Does the evidence differ for subgroups defined by age, sex, race, or ethnicity?
6. For people with asymptomatic CAS (defined as 60% to 99% stenosis), does the addition of medications (e.g., aspirin, statins) provide incremental benefit beyond current standard medical therapy that includes treatment of traditional risk factors (e.g., hypertension, hypercholesterolemia) in the reduction of fatal or nonfatal ipsilateral stroke?
a. Is there incremental benefit for persons at decreased risk for ipsilateral stroke caused by CAS?
b. Is there incremental benefit for persons at average risk for ipsilateral stroke caused by CAS?
c. Is there incremental benefit for persons at increased risk for ipsilateral stroke caused by CAS?
d. Does the evidence differ for subgroups defined by age, sex, race, or ethnicity?
7a. What are the harms associated with CEA or CAAS for the treatment of asymptomatic CAS?
7b. Do the harms differ for subgroups defined by age, sex, race, or ethnicity?
7c. Do the harms differ for subgroups defined by comorbidities?
8a. What are the harms associated with CEA or CAAS for the treatment of asymptomatic CAS?
8b. Do the harms differ for subgroups defined by age, sex, race, or ethnicity?
8c. Do the harms differ for subgroups defined by comorbidities?
The Research Approach identifies the study characteristics and criteria that the Evidence-based Practice Center will use to search for publications and to determine whether identified studies should be included or excluded from the Evidence Report. Criteria are overarching as well as specific to each of the key questions (KQs).
| Inclusion | Exclusion | |
|---|---|---|
| Population |
Asymptomatic adults with CAS that is potentially clinically important (defined as 60% to 99% stenosis). Asymptomatic indicates that patients have no significant neurologic symptoms referable to the carotid artery and have not experienced a cerebrovascular event (i.e., a stroke or transient ischemic attack).
Studies that enroll both symptomatic and asymptomatic subjects but analyze the asymptomatic group separately will be included. Among asymptomatic subjects, some trials enroll a minority of subjects who have not had symptoms for some specified time period (e.g., the past 180 days) but had prior symptoms or cerebrovascular events. Although our focus is on people who have never had cerebrovascular events, such studies will be included if they enroll 70% or more of subjects who never had symptoms referable to the carotid artery and never had a cerebrovascular event in the “asymptomatic” group. |
Children and adolescents; symptomatic adults with CAS; adults with history of transient ischemic attacks or stroke; studies of people with carotid occlusion; studies of people undergoing coronary artery bypass grafting and others confined to a focused population, such as those with radiation exposure or peripheral vascular disease; people with remote CEA or CAAS undergoing surveillance for restenosis. |
| Setting | Studies conducted in developed countries. | |
| Screening | Screening with carotid duplex ultrasonography, alone or with CTA or MRA, with or without confirmatory testing with angiography. Studies that use a single screening test as well as multiple tests in series (e.g., ultrasonography followed by MRA for persons with potentially significant ultrasound findings) will be included. | |
| Treatment/management interventions | CEA, CAAS, medical therapy (e.g., aspirin, statins, antiplatelet medications). | |
| Comparisons |
KQ 1: Screened versus nonscreened groups. KQ 2: Studies must determine/compare those at increased, average, or decreased risk or those at higher and lower risk of CAS (defined as 60%–99% stenosis). KQ 3: Studies on accuracy of screening must include a comparison with angiography; studies on reliability of screening must include measures of reproducibility (e.g., test-retest, comparison between different laboratories or readers). KQ 4: Studies must determine/compare those at increased, average, or decreased risk or those at higher and lower risk of ipsilateral stroke (KQ 4a) or periprocedural harms from CEA or CAAS (KQ 4b). KQ 5: Medical treatment/usual care. KQ 6: Studies must compare the addition of one or more medications to current standard medical therapy (that includes treatment of traditional risk factors) versus the addition of placebo to current standard medical therapy (that includes treatment of traditional risk factors). KQ 7: Screened versus nonscreened groups or those having angiography versus not having angiography. KQ 8: Medical treatment/usual care. |
No comparison; nonconcordant historical controls; comparative studies of CEA versus CAAS. |
| Outcomes |
KQs 1, 5, 6 (health outcomes): CAS-related fatal or nonfatal stroke; quality of life and functional status. KQ 2 (assessment of risk stratification tools): Adjusted hazard ratio (or risk ratio or odds ratio), discrimination, calibration, reclassification; tools must be externally validated. KQ 3 (diagnostic accuracy and reliability of screening tests): Sensitivity and specificity. KQ 4 (assessment of risk stratification tools): Adjusted hazard ratio (or risk ratio or odds ratio), discrimination, calibration, reclassification; tools must be externally validated. KQ 7 (harms of screening or confirmatory tests): False-positives leading to unnecessary treatment, nonfatal stroke, fatal stroke, persistent neurological complications, renal failure. KQ 8 (harms of CEA or CAAS): Perioperative complications including stroke, death, nonfatal myocardial infarction, cranial nerve injuries. |
Restenosis, quality-adjusted life years. |
| Study designs |
KQ 1: Randomized, controlled trials (RCTs) that compare screened versus nonscreened groups. KQ 2: Cohort studies that develop risk stratification tools and then validate the tools using an external population. Studies must follow a cohort of asymptomatic people to develop a tool, derived from a multivariate analysis, predicting risk of CAS. Risk stratification tools (or “risk prediction tools”) must combine multiple variables and allow for the calculation of risk for individual patients. KQ 3: Systematic reviews that compare screening tests (ultrasonography, MRA, or CTA) with angiography. Primary studies comparing screening tests with angiography that were published after the included systematic reviews will be included (i.e., bridge searches will be performed to determine what is new since the systematic reviews and whether it is consistent with the systematic reviews). KQ 4: Cohort studies that develop risk stratification tools for adults with asymptomatic CAS and then validate the tools using an external population. Studies must follow a cohort of people with asymptomatic CAS (defined as 60%–99% stenosis) to develop a tool, derived from a multivariate analysis, predicting risk of ipsilateral stroke (KQ 4a) or periprocedural harms (KQ 4b). Risk stratification tools (or “risk prediction tools”) must combine multiple variables and allow for the calculation of risk for individual patients. Risk stratification tools may include clinical factors (e.g., age, diabetes) and anatomic or imaging predictors (e.g., plaque area or morphology, silent embolic events, contralateral disease). KQ 5: Systematic reviews and RCTs of CEA or CAAS comparing surgical/interventional treatment with medical treatment. KQ 6: Systematic reviews and RCTs. KQ 7: Systematic reviews or multi-institution, prospective studies (RCTs or cohort studies) that report harms of screening or confirmatory tests. KQ 8: Systematic reviews or multi-institution, prospective studies (RCTs or cohort studies) that report 30-day or longer-term harms for asymptomatic patients undergoing CEA or CAAS. |
All other designs; studies enrolling both symptomatic and asymptomatic patients that do not analyze them separately. |
| Language | English | Non-English |
The draft Research Plan was posted for public comment on the U.S. Preventive Services Task Force (USPSTF) Web site from January 15 to February 11, 2013. The USPSTF received several comments requesting that it consider the evidence on medical therapies for CAS (in addition to CEA and CAAS). Several comments suggested that the USPSTF consider reviewing the evidence on ways to evaluate risk for harms from CEA or CAAS. Key questions addressing these two bodies of evidence were subsequently added to the Research Plan. A few comments requested that the USPSTF consider quality of life and functional status; these two outcomes were added to the inclusion criteria.
AHRQ Publication No. 13-05178-EF-4
Current as of April 2013
Internet Citation:
U.S. Preventive Services Task Force. Screening for Asymptomatic Carotid Artery Stenosis: Final Research Plan. AHRQ Publication No. 13-05178-EF-4. http://www.uspreventiveservicestaskforce.org/uspstf13/cas/casfinalresplan.htm