Title: Screening for Atrial Fibrillation
Funder: Department of Health and Social Care

Abstract: Our aim is to determine if screening for AF is effective and cost effective in reducing stroke and other key outcomes (both harm and benefit) compared to current practice. Our objectives are to: 1. Determine if screening for AF (including paroxysmal AF) is feasible in general practice in people aged 65 and over using a hand-held ECG recorder (Zenicor) 2. Perform an internal pilot cluster randomised controlled trial (RCT) to: -decide whether to proceed to an end-point powered cluster RCT -quantify psychological harms from screening -refine our screening programme 3. Perform a cluster RCT to determine if offering screening for AF (including paroxysmal AF) leads to reduced stroke and to quantify impact on mortality, cardiovascular disease and serious haemorrhage 4. Perform parallel qualitative studies to inform how to optimise screening both in the trial and if implemented nationally 5. Determine whether screening is cost effective Background 10% of ischaemic stroke is associated with newly diagnosed AF and a further 20% of ischaemic strokes are associated with known but untreated or undertreated AF. AF meets many of the classic criteria for screening, but there are weaknesses in the evidence base as identified by the UK Screening Committee. Uptake of anticoagulation is sub-optimal; screen-detected AF may have better prognosis than AF detected through routine clinical practice; and cost-effectiveness analyses (that consistently find that screening is cost-effective) have to make critical assumptions without RCT data on the effect of AF screening on stroke or mortality. An RCT powered to determine the impact of screening on clinical end-points such as stroke and mortality will resolve this controversy. Research Plan Workpackage (WP) 1: Feasibility and pilot work We will test feasibility of screening for AF (including paroxysmal AF) in six general practices in people aged 65 and over not on long term anticoagulation using a Zenicor hand-held ECG recorder. After a one-off screen, participants will be invited to check their heart rhythm using the ECG recorder over a two week period. We will test different recruitment methods (opportunistic; invitation sent by practice; patient invited to contact practice) with the aim of screening up to 400 patients per practice over a six month period. We will record key process criteria: proportion who consent to take part; proportion who complete both one-off and paroxysmal AF screening; proportion with AF identified; and use the results to refine the target population by reporting these in age strata. In an internal pilot, we will randomise larger practices (list size >7000) - 10 to screening and 20 to usual care. Prior to randomisation, we will send an information sheet and consent form to 800 patients in each practice that meet the inclusion criteria. Baseline data will be obtained from the GP electronic medical record in people who give consent. We will flag records with NHS digital for mortality and Hospital Episode Statistics (HES), and link with national stroke and myocardial infarction audits (SSNAP and MINAP). After twelve months, we will obtain data on new diagnoses of AF and use of anticoagulation from the GP electronic medical record. We will send postal questionnaires to a sample of 1,700 participants to assess psychological effects of screening. Key outcomes will be: AF detection rate; anticoagulation uptake rate, stratified by stroke risk (CHA2DS2-VASc score) and by AF type (paroxysmal or permanent). Parallel qualitative work (see WP3) will be carried out in both the feasibility and internal pilot to inform the design of the screening intervention. WP2: End-point powered cluster RCT We will recruit further practices to aim for 120,000 participants from 100 intervention and 200 control practices. We will follow up for an average of five years. Primary end-point: stroke. Secondary end points: all-cause mortality; cardiovascular events; bleeding requiring hospitalisation; dementia. All follow up will be remote from the patient. We will conduct sub-studies to determine what patient and practice characteristics are associated with high uptake of screening and the accuracy of different methods of verifying screening diagnosis of AF. WP3: Qualitative studies We will carry out case studies in eleven intervention practices drawn from feasibility, internal pilot studies and the main trial which will include ethnographic observation; interviews with health care professionals and patients; video-recording consultations concerning AF screening or anticoagulation treatment; video-elicitation interviews; observation of training. Specific issues will include: patient consent to screening; shared decision making on anticoagulation; what factors lead to high screening uptake. WP4: Health economics We will (i) adapt, (ii) update and (iii) incorporate our trial results into a previously published discrete-time Markov model to determine the long-term cost-effectiveness of screening in terms of cost per QALY gained. We will work closely with the National Screening Committee, who are the key body to implement our research findings. If cost effective, an AF screening programme with careful management of diagnosis and treatment may prevent over 10% of ischaemic strokes.

Lay abstract: Atrial fibrillation (AF) is a heart condition that causes irregular heartbeat. It affects up to 10 in 100 people over the age of 65, but does not necessarily produce symptoms. AF greatly increases risk of stroke, but treatment with blood thinning (&ldquo;anticoagulant&rdquo;) can stop this happening. 3 in 100 people aged 75 have AF without knowing it. About 10% of strokes happen in people unaware they have AF. Many clinicians think the NHS should promote AF screening. Following review, the UK National Screening Committee concluded there was insufficient information to be sure whether screening would do more good than harm for the whole group to be offered screening. They highlighted an absence of evidence that people who have AF detected by screening would benefit. Our research aims to find out if screening for AF in people aged 65 and over does prevent stroke and other problems like heart attacks and represent good value-for-money for the NHS. 1. Feasibility study We need to determine whether it is feasible to implement a new model of screening in general practice, and find out how many people are likely to take part. We will try out our screening programme in six practices. 2. Pilot study We will set up a screening programme in ten general practices and compare what happens in twenty practices in which we do not set up screening. This will help us to decide if: - the screening programme needs refinement; - screening is identifying the number of new cases of AF that we expected; - sufficient numbers of newly identified people with AF are started on anticoagulation; - screening causes any undue worry in people. 3. Randomised controlled trial We will carry out an experiment in 300 general practices involving 120,000 patients in which 100 practices undertake screening and 200 do not. We will follow up people for five years without having any further direct contact with them. We will see if screening leads to fewer strokes, heart attacks, and deaths, and whether it increases risk of serious bleeding (the main harm associated with &ldquo;anticoagulants&rdquo;). 4. Qualitative studies We will carry out case studies in practices taking part in screening to clarify how to carry out screening, both in the RCT, and in a potential national screening programme. These studies will involve observing what goes on in practices when carrying out screening, and interviewing staff and patients. We particularly want to explore: - issues around consent to screening; - sharing decision making about treatment if AF is found; - factors associated with uptake of screening; -patient concerns. 5. Cost effectiveness analysis We will determine, if screening does lead to fewer strokes, and whether this is good use of NHS resources.

Research activity codes: 4.4 POPULATION SCREENING
Health categories: STROKE;CARDIOVASCULAR