Randomised controlled trial of population screening for atrial fibrillation in people aged 70 years and over to reduce stroke: protocol for the SAFER trial

Jonathan Mant; Rakesh N Modi; Andrew Dymond; Natalie Armstrong; Jenni Burt; Peter Calvert; Martin Cowie; Wern Yew Ding; Duncan Edwards; Ben Freedman; Simon J Griffin; Sarah Hoare; F D Richard Hobbs; Rachel Johnson; Stephen Kaptoge; Gregory Y H Lip; Trudie Lobban; Mark Lown; Jenny Lund; Richard J McManus; Mark T Mills; Stephen Morris; Alison Powell; Riccardo Proietti; Stephen Sutton; Mike Sweeting; Howard Thom; Kate Williams; SAFER author group

doi:10.1136/bmjopen-2023-082047

Randomised controlled trial of population screening for atrial fibrillation in people aged 70 years and over to reduce stroke: protocol for the SAFER trial

BMJ Open. 2024 Apr 25;14(4):e082047. doi: 10.1136/bmjopen-2023-082047.

Authors

Jonathan Mant¹, Rakesh N Modi², Andrew Dymond¹, Natalie Armstrong³, Jenni Burt⁴, Peter Calvert⁵, Martin Cowie⁶, Wern Yew Ding⁵, Duncan Edwards¹, Ben Freedman⁷, Simon J Griffin^{8

9}, Sarah Hoare¹⁰, F D Richard Hobbs¹¹, Rachel Johnson¹², Stephen Kaptoge¹³, Gregory Y H Lip^{5

14}, Trudie Lobban¹⁵, Mark Lown¹⁶, Jenny Lund¹⁷, Richard J McManus¹¹, Mark T Mills⁵, Stephen Morris¹⁰, Alison Powell¹⁸, Riccardo Proietti⁵, Stephen Sutton¹⁰, Mike Sweeting¹³, Howard Thom¹², Kate Williams¹; SAFER author group

Affiliations

¹ Primary Care Unit, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK.
² Primary Care Unit, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK rnm30@medschl.cam.ac.uk.
³ Department of Population Health Sciences, University of Leicester, Leicester, UK.
⁴ THIS Labs, Cambridge, UK.
⁵ Liverpool Heart and Chest Hospital NHS Foundation Trust, Liverpool, UK.
⁶ School of Cardiovascular and Metabolic Medicine & Sciences, King's College London, London, UK.
⁷ Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia.
⁸ Institute of Public Health, University of Cambridge Primary Care Unit, Cambridge, UK.
⁹ MRC Epidemiology Unit, Cambridge, UK.
¹⁰ Department of Public Health and Primary Care, University of Cambridge Primary Care Unit, Cambridge, UK.
¹¹ Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
¹² University of Bristol, Bristol, UK.
¹³ Cambridge Biomedical Campus, Cambridge, UK.
¹⁴ Danish Centre for Health Services Research, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
¹⁵ Arrhythmia Alliance and AF Association, Stratford upon Avon, UK.
¹⁶ School of Primary Care, Population Sciences and Medical Education, University of Southampton, Southampton, UK.
¹⁷ Primary Care Unit, Department of Public Health & Primary Care, Strangeways Research Laboratory, Cambridge, UK.
¹⁸ THIS Institute, University of Cambridge, Cambridge, UK.

Abstract

Introduction: There is a lack of evidence that the benefits of screening for atrial fibrillation (AF) outweigh the harms. Following the completion of the Screening for Atrial Fibrillation with ECG to Reduce stroke (SAFER) pilot trial, the aim of the main SAFER trial is to establish whether population screening for AF reduces incidence of stroke risk.

Methods and analysis: Approximately 82 000 people aged 70 years and over and not on oral anticoagulation are being recruited from general practices in England. Patients on the palliative care register or residents in a nursing home are excluded. Eligible people are identified using electronic patient records from general practices and sent an invitation and consent form to participate by post. Consenting participants are randomised at a ratio of 2:1 (control:intervention) with clustering by household. Those randomised to the intervention arm are sent an information leaflet inviting them to participate in screening, which involves use of a handheld single-lead ECG four times a day for 3 weeks. ECG traces identified by an algorithm as possible AF are reviewed by cardiologists. Participants with AF are seen by a general practitioner for consideration of anticoagulation. The primary outcome is stroke. Major secondary outcomes are: death, major bleeding and cardiovascular events. Follow-up will be via electronic health records for an average of 4 years. The primary analysis will be by intention-to-treat using time-to-event modelling. Results from this trial will be combined with follow-up data from the cluster-randomised pilot trial by fixed-effects meta-analysis.

Ethics and dissemination: The London-Central National Health Service Research Ethics Committee (19/LO/1597) provided ethical approval. Dissemination will include public-friendly summaries, reports and engagement with the UK National Screening Committee.

Trial registration number: ISRCTN72104369.

Keywords: CARDIOLOGY; Mass Screening; Primary Care; Randomized Controlled Trial; Stroke.

Publication types

Research Support, Non-U.S. Gov't
Clinical Trial Protocol
Randomized Controlled Trial

MeSH terms

Aged
Aged, 80 and over
Anticoagulants / therapeutic use
Atrial Fibrillation* / complications
Atrial Fibrillation* / diagnosis
Electrocardiography
England / epidemiology
Female
Humans
Male
Mass Screening* / methods
Randomized Controlled Trials as Topic
Stroke* / prevention & control

Substances

Anticoagulants

Grants and funding

WT_/Wellcome Trust/United Kingdom