Evidence Synthesis Number 164 Screening for Atrial Fibrillation With Electrocardiography: An Evidence Review for the U.S. Preventive Services Task Force Prepared for: Agency for Healthcare Research and Quality U.S. Department of Health and Human Services 5600 Fishers Lane Rockville, MD 20857 www.ahrq.gov Contract No. HHSA-290-2015-00011-I, Task Order No. 7 Prepared by: RTI International–University of North Carolina Evidence-based Practice Center Research Triangle Park, NC 27709 Investigators: Daniel E. Jonas, MD, MPH Leila C. Kahwati, MD, MPH Jonathan D.Y. Yun, MD Jennifer Cook Middleton, PhD Manny Coker-Schwimmer, MPH Gary N. Asher, MD, MPH AHRQ Publication No. 17-05236-EF-1 August 2018 This report is based on research conducted by the RTI International–University of North Carolina Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. HHSA-290-2015-00011-I, Task Order No. 7). The findings and conclusions in this document are those of the authors, who are responsible for its contents, and do not necessarily represent the views of AHRQ. Therefore, no statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services. The information in this report is intended to help health care decisionmakers—patients and clinicians, health system leaders, and policymakers, among others—make well-informed decisions and thereby improve the quality of health care services. This report is not intended to be a substitute for the application of clinical judgment. Anyone who makes decisions concerning the provision of clinical care should consider this report in the same way as any medical reference and in conjunction with all other pertinent information (i.e., in the context of available resources and circumstances presented by individual patients). This report may be used, in whole or in part, as the basis for development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied. None of the investigators has any affiliations or financial involvement that conflicts with the material presented in this report. Acknowledgments The authors gratefully acknowledge the following individuals for their contributions to this project: Elisabeth Kato, MD, MRP, and Howard Tracer, MD, AHRQ Medical Officers; Tracy Wolff, MD, MPH, AHRQ Associate Scientific Director; current and former members of the U.S. Preventive Services Task Force who contributed to topic deliberations; expert reviewers David A Fitzmaurice, MBChB, MRCGP, MD, Richard Hobbs, MA, Stephen Morgan, MA, MB, BChir, MSc, MRCG, and Larisa G. Tereshchenko, MD, PhD; Federal partner reviewers at the Centers for Disease Control and Prevention; and RTI International–University of North Carolina EPC staff Carol Woodell, BSPH; Josh Green, BA; Christiane Voisin, MSLS; Claire Korzen, BA; Sharon Barrell, and Loraine Monroe. Suggested Citation Jonas DE, Leila C. Kahwati LC, Yun JD, Middleton JC, Coker-Schwimmer M, Asher GN. Screening for Atrial Fibrillation With Electrocardiography: An Evidence Review for the U.S. Preventive Services Task Force. Evidence Synthesis No. 164. AHRQ Publication No. 17-05236- EF-1. Rockville, MD: Agency for Healthcare Research and Quality; 2018. Screening for Atrial Fibrillation With ECG ii RTI–UNC EPC Structured Abstract Purpose: To systematically review the evidence on screening for and stroke prevention treatment of nonvalvular atrial fibrillation (AF) in adults age 65 years or older for populations and settings relevant to primary care in the United States. Data Sources: PubMed/MEDLINE, the Cochrane Library, and trial registries through May 24, 2017; reference lists of retrieved articles; outside experts; and reviewers, with surveillance of the literature through June 6, 2018. Study Selection: Two investigators selected English-language studies using a priori criteria. Eligible studies included controlled trials of screening for or treatment of AF, controlled prospective cohort studies evaluating detection rates of previously unknown AF or harms of screening or treatment, and systematic reviews of trials evaluating benefits or harms of treatment. Eligible screening tests included electrocardiogram (ECG) screening (e.g., 12-lead ECG, intermittent handheld ECG) or screening with both pulse palpation and ECG for all participants. Eligible treatment studies compared warfarin, aspirin, or novel oral anticoagulants (NOACs: apixaban, dabigatran, edoxaban, or rivaroxaban) with placebo or no treatment. Studies focused on persons younger than age 65 or those with a history of stroke, transient ischemic attack, known heart disease, or heart failure were excluded. Data Extraction: One investigator extracted data and a second checked accuracy. Two reviewers independently rated quality for all included studies using predefined criteria. Data Synthesis: Seventeen unique studies (described in 22 publications) were included. No eligible studies evaluated screening compared with no screening and focused on health outcomes. Systematic screening with ECG identified more new cases of AF than no screening (absolute increase with 12-lead ECG, 0.6% [0.1% to 0.98%] over 12 months; absolute increase with twice-weekly single-lead ECG, 2.8% [95% CI, 0.9% to 4.7%] over 12 months), but a systematic approach using ECG did not detect more cases than an opportunistic approach focused on pulse palpation. Warfarin treatment for an average of 1.5 years was associated with a reduced risk of ischemic stroke (pooled relative risk [RR], 0.32 [0.20 to 0.51]) and all-cause mortality (pooled RR, 0.68 [0.50 to 0.93]), and an increased risk of major bleeding (pooled RR, 1.8 [0.85 to 3.7]) compared with controls (5 trials; 2,415 participants). Treatment trial participants were not screen-detected; mean age was 67 to 74 years; very few had a history of TIA or stroke (3%-8%); most had long-standing persistent AF; and baseline stroke risk scores were not reported. For a population of 1,000 adults age 65 or older with an annual stroke risk of 4 percent, this translates to an absolute reduction of 28 ischemic strokes and 16 deaths per year and an absolute increase of five major bleeding events per year. Aspirin treatment for an average of 1.5 years was associated with a reduced risk of ischemic stroke (pooled RR, 0.76 [0.52 to 1.1]) and all-cause mortality (pooled RR, 0.84 [0.62 to 1.14]) compared with controls, but the differences were not statistically significant (3 trials; 2,663 participants). A network meta- analysis found that all treatments reduced the risk of a composite outcome (any stroke and systemic embolism) and all-cause mortality. For NOACs, it found statistically significant associations with reduction in the composite outcome compared with placebo/control (adjusted odds ratios [ORs] from 0.32 to 0.44), and an increased risk of bleeding compared with Screening for Atrial Fibrillation With ECG iii RTI–UNC EPC placebo/control (adjusted ORs from 1.38 to 2.21), but confidence intervals for the risk of bleeding were wide and differences between groups were not statistically significant. Limitations: This review is limited in the ability to describe the direct evidence on the effectiveness or harms of screening for AF because we identified no eligible studies that aimed to address the overarching question. For potential harms of screening (e.g., overdiagnosis from misinterpretation of ECGs, subsequent interventions leading to harms), no eligible studies provided information that allowed comparison between screening and no-screening. No eligible stroke prevention treatment studies focused on asymptomatic, screen-detected participants. The included trials that evaluated warfarin benefits and harms had an average of 1.5 years of followup and were stopped early. Estimates for benefits and harms of lifelong anticoagulation and for screen-detected persons were not available. Conclusions: There is uncertainty about the benefits and harms of screening for AF with ECG. Although screening with ECG can detect previously unknown cases of AF, it has not been shown to detect more cases than opportunistic screening that is focused on pulse palpation. Most older adults with previously unknown AF have a stroke risk above the threshold for anticoagulation. Multiple treatments for AF reduce the risk of stroke and all-cause mortality, and increase the risk of bleeding, but trials have not assessed whether treatment of screen-detected asymptomatic older adults results in better health outcomes than treatment after detection by usual care or after symptoms develop. Screening for Atrial Fibrillation With ECG iv RTI–UNC EPC Table of Contents Chapter 1. Introduction......................................................................................................... 1 Scope and Purpose ............................................................................................................... 1 Condition Definition ............................................................................................................ 1 Etiology and Natural History................................................................................................ 1 Risk Factors......................................................................................................................... 2 Prevalence and Burden........................................................................................................