Estimated stroke risk, yield, and number needed to screen for atrial fibrillation detected through single time screening: a multicountry patient-level meta-analysis of 141,220 screened individuals.

Change log
Chao, Tze-Fan 
Chen, Shih-Ann 
Chen, Yi 

BACKGROUND: The precise age distribution and calculated stroke risk of screen-detected atrial fibrillation (AF) is not known. Therefore, it is not possible to determine the number needed to screen (NNS) to identify one treatable new AF case (NNS-Rx) (i.e., Class-1 oral anticoagulation [OAC] treatment recommendation) in each age stratum. If the NNS-Rx is known for each age stratum, precise cost-effectiveness and sensitivity simulations can be performed based on the age distribution of the population/region to be screened. Such calculations are required by national authorities and organisations responsible for health system budgets to determine the best age cutoffs for screening programs and decide whether programs of screening should be funded. Therefore, we aimed to determine the exact yield and calculated stroke-risk profile of screen-detected AF and NNS-Rx in 5-year age strata. METHODS AND FINDINGS: A systematic review of Medline, Pubmed, and Embase was performed (January 2007 to February 2018), and AF-SCREEN international collaboration members were contacted to identify additional studies. Twenty-four eligible studies were identified that performed a single time point screen for AF in a general ambulant population, including people ≥65 years. Authors from eligible studies were invited to collaborate and share patient-level data. Statistical analysis was performed using random effects logistic regression for AF detection rate, and Poisson regression modelling for CHA2DS2-VASc scores. Nineteen studies (14 countries from a mix of low- to middle- and high-income countries) collaborated, with 141,220 participants screened and 1,539 new AF cases. Pooled yield of screening was greater in males across all age strata. The age/sex-adjusted detection rate for screen-detected AF in ≥65-year-olds was 1.44% (95% CI, 1.13%-1.82%) and 0.41% (95% CI, 0.31%-0.53%) for <65-year-olds. New AF detection rate increased progressively with age from 0.34% (<60 years) to 2.73% (≥85 years). Neither the choice of screening methodology or device, the geographical region, nor the screening setting influenced the detection rate of AF. Mean CHA2DS2-VASc scores (n = 1,369) increased with age from 1.1 (<60 years) to 3.9 (≥85 years); 72% of ≥65 years had ≥1 additional stroke risk factor other than age/sex. All new AF ≥75 years and 66% between 65 and 74 years had a Class-1 OAC recommendation. The NNS-Rx is 83 for ≥65 years, 926 for 60-64 years; and 1,089 for <60 years. The main limitation of this study is there are insufficient data on sociodemographic variables of the populations and possible ascertainment biases to explain the variance in the samples. CONCLUSIONS: People with screen-detected AF are at elevated calculated stroke risk: above age 65, the majority have a Class-1 OAC recommendation for stroke prevention, and >70% have ≥1 additional stroke risk factor other than age/sex. Our data, based on the largest number of screen-detected AF collected to date, show the precise relationship between yield and estimated stroke risk profile with age, and strong dependence for NNS-RX on the age distribution of the population to be screened: essential information for precise cost-effectiveness calculations.

Adult, Age Factors, Aged, Aged, 80 and over, Atrial Fibrillation, Electrocardiography, Female, Humans, Male, Mass Screening, Middle Aged, Predictive Value of Tests, Prognosis, Risk Assessment, Risk Factors, Sex Factors, Stroke, Young Adult
Journal Title
PLoS Med
Conference Name
Journal ISSN
Volume Title
Public Library of Science (PLoS)
All rights reserved
Medical Research Council (G9900264)
NL is funded by a NSW Health Early Career Fellowship (H16/52168) FDRH acknowledges his part-funding from the National Institute for Health Research (NIHR) School for Primary Care Research, the NIHR Collaboration for Leadership in Health Research and Care (CLARHC) Oxford, the NIHR Oxford Biomedical Research Centre (BRC, UHT), and the NIHR Oxford Medtech and In-Vitro Diagnostics Co-operative (MIC) PSW is funded by the Federal Ministry of Education and Research (BMBF 01EO1503) and he is PI of the German Center for Cardiovascular Research (DZHK) BPY is supported by the Hong Kong Research Grants Council - General Research Fund (RGC Ref No.14118314) RKS received a grant from the University Hospital Foundation. JSH has a personnel award from the Heart and Stroke Foundation, Ontario Provincial office (MC7450) JJO is supported by an Australian Government Research Training Program scholarship DDM receives research support from NIH 1U01HL105268-01, KL2RR031981, R01HL126911, R01HL137794, HRS174612, and Grant 1522052 from the National Science Foundation AKR acknowledges funding by the NIHR Oxford Biomedical Research Centre LAPDT received a grant from the Andalusian Public Progress and Health Foundation for the financing of biomedical and health sciences research in Andalusia (PI-0117-2011), the XIII grant from the Spanish Primary Care Network, a grant "Isabel Fernández" of the Spanish Society of Family and Community Medicine (semFYC), and another of the Andalusian Society of Family and Community Medicine (SAMFyC) . This project received some funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 648131), German Ministry of Research and Education (BMBF 01ZX1408A), and German Center for Cardiovascular Research (DZHK e.V.) (81Z1710103) (RBS) The funding bodies had no role or influence in the collation, analysis or reporting of the data. The Gutenberg Health Study is funded through the government of Rhineland-Palatinate (“Stiftung Rheinland-Pfalz für Innovation”, contract AZ 961-386261/733), the research programs “Wissen schafft Zukunft” and “Center for Translational Vascular Biology (CTVB)” of the Johannes Gutenberg-University of Mainz, and its contract with Boehringer Ingelheim https://www.boehringeringelheim. and PHILIPS Medical Systems, including an unrestricted grant for the Gutenberg Health Study. The PIAAF-Pharmacy study was supported by the Canadian Stroke Prevention Intervention Network, Boehringer Ingelheim and in-kind support from CardioComm The SEARCH-AF study was supported by an investigator-initiated grant from Bristol-Myers Squibb/Pfizer, and a small investigator-initiated project award from Boehringer Ingelheim; AliveCor provided ECG Heart Monitors for study purposes: the investigators are not affiliated with, nor have any financial or other interest in AliveCor The AF-SMART study was supported by a National Heart Foundation of Australia/ NSW Health Cardiovascular Research Network Project Grant (101133); AliveCor provided free Kardia Heart Monitors for study purposes The Belgian Heart Rhythm Week Screening Programme was funded with unconditional grants from Boehringer Ingelheim, St Jude Medical, Sanofi, MSD, and MSH; none of the companies had any role in the conduction of the screening programme, study design, collection, and interpretation of data or writing and revision of the manuscript. All the researchers were completely independent from the funders. DANCAVAS was supported by the Danish Heart Foundation PIAAF-FP was funded by the Canadian Stroke Prevention Intervention Network, Boehringer-Ingelheim and in-kind support from CardioComm and ManthaMed . OFRECE study was promoted by the “Agencia de investigación de la Sociedad Española de Cardiología”