Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): National Institute for Health and Care Research Oxford Biomedical Research Centre ECG patches (and respective monitoring data analysis) were granted free of charge by the manufacturer (iRhythm) Background Incidence of stroke could be reduced by detection of subclinical atrial fibrillation (AF) and appropriate anticoagulation. Opportunistic screening by pulse-taking or ECG is recommended by some international guidelines. In contrast, there is uncertainty regarding the benefits and harms of systematic screening across populations and/or using longer monitoring durations. Purpose To assess if screening using a one-off single-lead continuous non-invasive ECG patch worn for 14 days increases AF detection at 2.5 years compared to standard care, and whether this approach is cost-effective. Methods AMALFI is an ongoing mail-based open-label randomised controlled trial of remote AF screening in England. Streamlined design includes integration with national electronic health data and care pathways for participant identification, invitation, and management. The target population are individuals aged ≥65 years with CHA2DS2VASc score of ≥3 in men and ≥4 in women, and with no prior history of AF or allergy to latex. Participants in the intervention arm self-apply the ECG patch and return it for analysis after 14 days. AF findings (duration ≥30 seconds at any rate) are communicated to primary care physicians, with further clinical management at their discretion. Participants in the control arm receive usual care (which is expected to include opportunistic AF screening). The primary outcome is the proportion of participants with newly-detected AF recorded in primary care electronic health records in each group at 2.5 years after randomisation. Results From 2019 to 2022, AMALFI invited 22,188 people, of whom 5,040 (23%) were randomised. Baseline characteristics included age 77±6 years, 47% female, and median CHA2SD2VASc score 3 (Table 1). Of 2520 individuals randomised to the intervention, 2127 (84%) wore and returned the patch. Median wear time was 13.9 days and median proportion of time analysable was 98.8%. AF was present in 102 patch reports, representing 4.8% of reports received and 4% of the intervention arm (in line with a priori estimates for power calculations for the primary outcome); median AF burden was 11.3%. AF was present at commencement of recording in 40% of these reports, by the end of the first day in 58%, and by the end of the first week in 83% (Figure 1). Incidental findings included supraventricular tachycardia (in 90% of reports), non-sustained ventricular tachycardia (VT; in 32%), sustained VT (in 0.1%), Mobitz II/high-grade/3rd degree AV block (in 1.1%), and pauses >6s (in 0.3%). Conclusion AMALFI’s innovative design facilitated recruitment and demonstrates that a remote ECG patch-based AF screening strategy is feasible, resulting in a new diagnosis of AF in ~4% of individuals selected due to moderate-to-high clinical stroke risk. Longer term follow-up will provide data on the incremental value and cost-effectiveness of AF diagnosis by systematic screening compared to routine opportunistic detection.