This review updates the 1996 USPSTF review of screening for CAS, focusing on duplex ultrasound as the screening test (with various confirmatory tests) and CEA as the treatment for clinically important CAS. Medical interventions and screening with carotid auscultation were not reviewed in this report. The USPSTF has reviewed screening for several known risk factors of carotid artery stenosis and stroke, including hyperlipidemia, hypertension, aspirin prophylaxis, and smoking. The evidence reports and recommendations are available at the Agency for Healthcare Research and Quality (AHRQ) website at www.preventiveservices.ahrq.gov.
An analytic framework was developed for this review following USPSTF methods and is shown in Figure 1.28 The USPSTF developed 4 key questions (KQ) from the analytic framework to guide its consideration of the benefits and harms of screening with ultrasound for CAS. The key questions were:
- KQ1. Is there direct evidence that screening adults with duplex ultrasound for asymptomatic CAS reduces fatal and/or nonfatal stroke?
- KQ2. What is the accuracy and reliability of duplex ultrasound to detect clinically important CAS?
- KQ3. For people with asymptomatic CAS 60%–99%, does intervention with CEA reduce CAS-related morbidity or mortality?
- KQ4. Does screening or CEA for asymptomatic CAS 60%–99% result in harm?
The USPSTF designated three key questions (1–3) as subsidiary questions for which they requested non-systematic reviews to assist them in updating their recommendations. KQ4 was the only key question for which the USPSTF requested a systematic evidence review.
Data Sources and Searches
We searched for English language literature published January 1, 1994 to April 2, 2007 in MEDLINE that addressed key questions 1, 2, and 3. In addition we identified additional studies through the reference lists of major review articles and through consultations with experts. For key question 3, we performed a MEDLINE search for RCTs, systematic reviews and meta-analyses that compared CEA with medical therapy for asymptomatic people with CAS. We identified one in-process RCT by its inclusion in a systematic review, and included it when it was published.
For key question 4, we performed a systematic search for English language articles published between January 1, 1994, and April 2, 2007, through a MEDLINE search using the focused MeSH terms “endarterectomy, carotid” and “outcome and process assessment.” In addition we selected a key study from this search and identified related articles through MEDLINE. Additional studies were identified through a search of the Cochrane database, through discussions with experts, and by hand-searching of reference lists from major review articles and studies.
Titles and abstracts of articles retrieved for KQ1–3 were non-systematically selected and reviewed by two reviewers. The process was considered non-systematic because articles were selected for review and abstracted by one reviewer. Articles for KQ1 were selected for inclusion if they were RCTs, compared screened versus non-screened groups, used ultrasound, MRA or computed tomography as screening modalities, reported outcomes of strokes or death in asymptomatic subjects, and were performed in a population generalizable to U.S. For KQ2, the authors included systematic reviews that compared screening tests (Ultrasound, MRA, or computed tomography screening) to angiography in asymptomatic subjects and were performed in a population generalizable to U.S. Articles for KQ3 were selected for inclusion if they were RCTs of CEA comparing surgical treatment to medical treatment, reported 30-day complication rates (stroke and death) of CEA, included only asymptomatic patients, and were performed in a population generalizable to the U.S.
For KQ4, three reviewers independently reviewed the abstracts and selected articles from titles and abstracts based on inclusion and exclusion criteria. In general, studies were selected if they were large, multi-institution, prospective studies that reported 30 day mortality/stroke outcomes for asymptomatic patients undergoing CEA. Studies were excluded if they did not report outcomes by symptomatic status, included patients receiving CEA combined with other major surgeries, were not performed in the U.S., included patients with restenosis, or were studies of patient populations at extremely high risk. Detailed search terms and inclusion/exclusion criteria are described in Appendix 1. Abstracts that were selected by fewer than three reviewers were discussed and selected based on consensus.
Data Extraction and Quality Assessment
For all citations that met the eligibility criteria, the full articles were reviewed and quality-rated independently by two reviewers. Consensus about article inclusion, content, and quality was achieved through discussion by the two reviewers; disagreements were resolved by the involvement of a third reviewer. Data on the following items were extracted from the included studies for KQ4: source population, sample size, average age, proportion white, proportion male, average degree of stenosis, and the proportion of subjects with important comorbidities, including contralateral stenosis, smoking, diabetes, hypertension, and coronary artery disease. Quality evaluations of articles for all KQs were performed using standard USPSTF methodology on internal and external validity.28 We evaluated the quality of RCTs and cohort studies on the following items: initial assembly of comparable groups, maintenance of comparable groups, important differential loss to follow-up or overall high loss to follow-up, measurements (equality, reliability, and validity of outcome measurements), clear definition of the interventions and appropriateness of outcomes. We evaluated systematic reviews and meta-analyses on the following items: comprehensiveness of sources considered, search strategy, standard appraisal of included studies, validity of conclusions, recency and relevance. More complete criteria and definitions for USPSTF quality ratings are listed in the Appendix 2.
Data Synthesis and Analysis
Data from the included studies for KQ1–3 were synthesized qualitatively in tabular and narrative format because of the non-systematic nature of the review. Data from the systematically reviewed KQ4 was also synthesized qualitatively and not quantitatively because of the different patient characteristics and varied outcome assessments. Synthesized evidence was organized by key question.
Role of the Funding Source
The general work of the USPSTF is supported by the Agency for Healthcare Research and Quality. This specific review did not receive separate funding.
Agency for Healthcare Research and Quality (US), Rockville (MD)
Wolff T, Guirguis-Blake J, Miller T, et al. Screening For Asymptomatic Carotid Artery Stenosis [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2007 Dec. (Evidence Syntheses, No. 50.) 3, Methods.