Final Research Plan
Atrial Fibrillation: Screening With Electrocardiography
July 14, 2016
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.
The final Research Plan will be used to guide a systematic review of the evidence by researchers at an Evidence-based Practice Center. The resulting Evidence Review will form the basis of the USPSTF Recommendation Statement on this topic.
The draft Research Plan was available for comment from May 5 until June 1, 2016 at 8:00 p.m., ET.
Abbreviations: ECG = electrocardiography; KQ = key question.
This figure is the analytic framework depicting the five key questions that will guide the evidence review outlined in this research plan. In general, the figure illustrates the overarching question of whether screening for atrial fibrillation with ECG in asymptomatic adults age 65 years and older leads to improved health outcomes (KQ4). Health outcomes include all-cause mortality, stroke, and morbidity and mortality related to stroke. The framework starts on the left with the patient population of interest: asymptomatic adults age 65 years and older. Moving from left to right, the figure depicts the ability of screening with ECG to diagnose atrial fibrillation (KQ5). There are potential harms of screening with ECG (KQ6). For older adults with screen-detected atrial fibrillation, treatment with anticoagulation or antiplatelet therapy may improve health outcomes (KQ7). Treatment may also result in harms (KQ8).
- Does screening for atrial fibrillation with ECG improve health outcomes (i.e., reduce all-cause mortality or morbidity or mortality from strokes) in asymptomatic older adults?
- Does improvement in health outcomes vary for subgroups defined by stroke risk (e.g., based on CHA2DS2-VASc score), age, sex, or race/ethnicity?
- Does systematic screening for atrial fibrillation with ECG identify older adults with previously undiagnosed atrial fibrillation more effectively than usual care?
- What are the harms of screening for atrial fibrillation with ECG in older adults?
- Do the harms of screening vary for subgroups defined by stroke risk (e.g., based on CHA2DS2-VASc score), age, sex, or race/ethnicity?
- What are the benefits of anticoagulation or antiplatelet therapy on health outcomes in asymptomatic, screen-detected older adults with atrial fibrillation?
- Do the benefits of anticoagulation or antiplatelet therapy vary for subgroups defined by stroke risk (e.g., based on CHA2DS2-VASc score), age, sex, or race/ethnicity?
- What are the harms of anticoagulation or antiplatelet therapy in asymptomatic, screen-detected older adults with atrial fibrillation?
- Do the harms of anticoagulation or antiplatelet therapy vary for subgroups defined by stroke risk (e.g., based on CHA2DS2-VASc score), age, sex, or race/ethnicity?
Contextual questions will not be systematically reviewed and are not shown in the Analytic Frameworks.
3. What is the prevalence of previously unrecognized or undiagnosed atrial fibrillation among asymptomatic adults, by age (groups), in primary care and community settings?
4. What is the stroke risk in asymptomatic older adults with previously unrecognized or undiagnosed atrial fibrillation?
5a. What are the recommendations on use of rate or rhythm control for the treatment of atrial fibrillation in asymptomatic adults age 65 years and older?
b. How often are such treatments used in the United States in asymptomatic adults age 65 years and older?
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 Review. Criteria are overarching as well as specific to each of the key questions (KQs).
|Condition definition||Atrial fibrillation (paroxysmal or persistent)||Other cardiac arrhythmias, nonarrhythmia-related CVD (e.g., coronary heart disease, hypertension)|
|Populations||KQs 4–6: Unselected or explicitly asymptomatic older adults (age ≥65 years); older adults selected for increased risk of nonvalvular atrial fibrillation (e.g., those with obesity, smoking, alcohol use, hypertension); studies of mixed populations of asymptomatic and symptomatic persons are eligible if results are reported separately for asymptomatic persons or <10% of the sample is symptomatic
KQs 7, 8: Older adults with atrial fibrillation. To approximate screen-detected persons with atrial fibrillation, we will aim to stratify analyses based on whether participants are asymptomatic/screen-detected vs. symptomatic (if possible); however, knowing that most studies enroll mixed populations or do not clearly enroll screen-detected or asymptomatic populations, we will not exclude studies based on whether participants were screen detected. To approximate “screening” vs. “disease management” populations, we will limit our analyses to studies of individuals not selected because of known heart disease, heart failure, and/or previous stroke or transient ischemic attack
|KQs 4–6: Symptomatic adults; adults with known (history of) atrial fibrillation; children, adolescents, and adults age <65 years; adults at high(est) risk for atrial fibrillation (including but not limited to those with mitral valve disease or repair/replacement); and adults with history of stroke or transient ischemic attack
KQs 7, 8: Adults needing antiplatelet or anticoagulation medications for conditions other than atrial fibrillation; adults with atrial fibrillation and known heart disease, heart failure, and/or previous stroke or transient ischemic attack
|Screening test or intervention||KQs 4–6: Systematic ECG screening using any approach (e.g., in-office single-application 12-lead ECG, continuous ECG, intermittent use of handheld ECG); systematic screening with both pulse palpation and ECG for all participants
KQs 7, 8: Medical treatment with antiplatelet agents (aspirin) or anticoagulants (apixaban, dabigatran, edoxaban, rivaroxaban, warfarin). Results will be stratified by type of medication.
|KQs 4–6: Physical examination (including pulse palpation); blood pressure monitoring, pulse oximetry; all other technologies (e.g., consumer devices, such as smartphones); studies that only use ECG for participants with irregular pulse (as opposed to all participants)
KQs 7, 8: Nonpharmacologic treatment to prevent stroke (e.g., implantable devices), treatment or management of atrial fibrillation for reasons other than prevention of stroke (e.g., rate or rhythm control, cardioversion, ablation)
|Comparisons||KQs 4–6: Screened vs. nonscreened groups, systematic screening vs. usual care (which may include opportunistic screening; that is, pulse palpation, automated blood pressure measurement, or cardiac auscultation during the course of a physical examination, or examination for another reason, with subsequent ECG if an irregular heart beat or pulse is noted)
KQs 7, 8: No treatment
|All KQs: No comparison, nonconcordant historical control
KQs 7, 8: Active treatment (i.e., antiplatelet or anticoagulation medications)
|Outcomes||KQ 4: All-cause mortality, stroke, and stroke-related morbidity or mortality
KQ 5: Comparative/relative yield (i.e., number of persons diagnosed with atrial fibrillation in one group vs. another [unscreened/differently screened] group)
KQ 6: Anxiety, labeling, harms of subsequent procedures or interventions initiated as a result of screening (e.g., subsequent ablation with complications)
KQ 7: All-cause mortality, cardioembolic stroke, and cardioembolic stroke-related morbidity or mortality
KQ 8: Any harms requiring unexpected or unwanted medical attention (e.g., hemorrhagic stroke, major bleeding, allergic reaction)
|KQs 6, 8: Nonserious events (e.g., bleeding not requiring or resulting in medical attention)|
|Study designs||All KQs: Randomized, controlled trials and controlled clinical trials
KQs 5, 6: Large prospective cohort studies are also eligible
KQ 7: Systematic reviews* of trials are also eligible
|All other designs, narrative reviews, case reports, case series, editorials, letters, cross-sectional studies, case-control studies, and retrospective cohort studies|
|Setting||KQs 4–6: Studies performed in primary care settings
KQs 7, 8: Studies performed in primary care or specialty settings
|KQs 4–6: Studies performed in specialty settings, studies of patients undergoing preoperative evaluation, and inpatient settings
KQs 7, 8: Studies conducted primarily in inpatient settings
|Country||Studies conducted in countries categorized as “Very High” on the 2014 Human Development Index (as defined by the United Nations Development Program)||Studies conducted in countries that are not categorized as “Very High” on the 2014 Human Development Index|
|Study quality||Good or fair||Poor (according to design-specific USPSTF criteria)|
* We will rely on the most recent, good-quality systematic reviews to address KQs 7 and 8. Primary studies of other eligible designs published after the search date cutoffs of included systematic reviews will also be eligible.
The draft Research Plan was posted for public comment on the USPSTF Web site from May 5, 2016 to June 1, 2016. Several comments suggested evaluating some of the KQs for subpopulations defined by differences in risk category, age, sex, or race/ethnicity. In response, the USPSTF added new sub-KQs to explore whether findings vary for these subgroups. In response to comments, the USPSTF replaced the term “cerebral vascular accident” with “stroke,” “cardioembolic stroke,” or “hemorrhagic stroke,” as appropriate. Since the focus of the evidence review is on using ECG to screen asymptomatic persons, the USPSTF decided not to include other devices for detecting atrial fibrillation as an intervention or add symptoms of atrial fibrillation as an outcome, as was requested in some comments.