Highlight
This randomized clinical trial investigated remote screening for asymptomatic atrial fibrillation (AF) using a patch-based continuous ambulatory ECG monitor mailed to older adults at moderate to high stroke risk. Key findings include a modest increase in AF diagnosis over 2.5 years and higher oral anticoagulation exposure in the intervention group, although no significant difference in stroke occurrence was observed.
Study Background
Atrial fibrillation is a prevalent cardiac arrhythmia associated with a substantially increased risk of ischemic stroke. Many individuals with AF remain asymptomatic, delaying diagnosis and timely initiation of stroke-preventive anticoagulation therapy. Effective screening strategies that increase detection of subclinical AF and subsequent anticoagulation could reduce stroke incidence. However, optimal screening modalities, especially those feasible for broad implementation, remain uncertain. Continuous ambulatory ECG patches offer a noninvasive approach to detect paroxysmal AF episodes over days to weeks. The AMALFI trial sought to evaluate the long-term impact of remote, mail-distributed ECG patch screening in a primary care setting targeting older adults with elevated stroke risk, addressing the knowledge gap regarding the effectiveness and practicality of population-wide AF screening programs.
Study Design
AMALFI was a parallel-group, unblinded, remote randomized clinical trial conducted across 27 UK primary care practices from May 2019 through February 2022, with final follow-up in August 2024. Eligible participants were individuals aged 65 years or older, with a CHA2DS2-VASc score of 3 or higher for men and 4 or higher for women, who had no prior diagnosis of AF or atrial flutter. Identification was facilitated by automated electronic health record searches, ensuring systematic recruitment.
A total of 5,040 participants were randomized evenly to receive either a 14-day, patch-based continuous ambulatory ECG monitor shipped by mail (intervention group, n=2,520) or usual care without screening (control group, n=2,520). The intervention group was instructed to wear and return the patch monitor. The primary outcome was the proportion of participants with documented AF in primary care records within 2.5 years postrandomization. Secondary and exploratory outcomes included oral anticoagulation exposure and incidence of stroke during follow-up.
Key Findings
Out of 22,044 individuals invited, 5,040 (22.9%) consented and were randomized. The cohort had a mean age of 78 years, with 47% female participants, and a median CHA2DS2-VASc score of 4, indicating a moderate to high stroke risk population.
In the intervention arm, 84.4% (2,126/2,520) successfully wore and returned the ECG patch. AF was detected by the patch in 89 participants (4.2%), with over half exhibiting an AF burden under 10%, reflecting brief or infrequent episodes of arrhythmia.
The primary analysis showed that 6.8% of participants in the intervention group had postrandomization AF recorded in their primary care records within 2.5 years compared with 5.4% in the control group. This corresponded to a ratio of proportions of 1.26 (95% CI, 1.02–1.57; P = 0.03), indicating a statistically significant but modest increase in AF diagnosis attributable to screening. The effect was consistent across prespecified subgroups stratified by demographic and clinical characteristics.
Regarding anticoagulation, the mean cumulative exposure by 2.5 years was 1.63 months (95% CI, 1.50–1.76) in the intervention group versus 1.14 months (95% CI, 1.01–1.26) in the control group, with a difference of 0.50 months (95% CI, 0.24–0.75; P < 0.001). This suggests screening facilitated earlier initiation or longer duration of oral anticoagulants among newly diagnosed AF patients.
Stroke occurrence was low and similar between groups: 2.7% in the intervention arm versus 2.5% in controls (rate ratio, 1.08; 95% CI, 0.76–1.53), without statistically significant difference. This finding indicates that the modest increase in AF detection and anticoagulation use did not translate into reduced stroke rates within the trial timeframe.
Expert Commentary
The AMALFI trial provides robust evidence on the feasibility and modest benefit of remote, mail-based ECG patch screening for asymptomatic AF in an aging population at elevated stroke risk. The high adherence to patch use underscores the acceptability of this approach in routine primary care settings.
Importantly, while screening led to a statistically significant increase in AF diagnosis and anticoagulation use, the absolute magnitude was modest, and no stroke reduction was observed over 2.5 years. The relatively low AF burden detected in many cases raises questions about the clinical significance and necessity of anticoagulation in minimal arrhythmia detected through prolonged monitoring.
These findings align with existing evidence suggesting that AF screening can identify additional cases but that translation into clinical benefit depends on multiple factors, including AF burden, anticoagulation adherence, and follow-up duration. Longer-term studies or larger sample sizes may be required to detect stroke prevention benefits.
Limitations include potential underdetection of low-burden AF in controls due to reliance on routine care data and lack of blinding, which might affect outcome ascertainment or treatment decisions. Moreover, the generalizability to populations with differing healthcare systems or sociodemographic characteristics needs consideration.
Conclusion
Remote, mail-based screening using a 14-day continuous ECG patch in older adults at moderate to high stroke risk modestly increases the detection of atrial fibrillation and short-term oral anticoagulation exposure but does not reduce stroke incidence over 2.5 years. This trial reinforces the potential and challenges of implementing large-scale AF screening programs and highlights the need for further research on optimizing screening strategies, timing of anticoagulant initiation, and long-term clinical outcomes.
Funding and Trial Registration
The AMALFI trial was registered with ISRCTN (Identifier: 15544176). Funding details were not specified in the source reference.
References
Wijesurendra R, Pessoa-Amorim G, Buck G, Harper C, Bulbulia R, Offer A, Jones NR, A’Court C, Kurien R, Taylor K, Casadei B, Bowman L. Remote Screening for Asymptomatic Atrial Fibrillation: The AMALFI Randomized Clinical Trial. JAMA. 2025 Oct 21;334(15):1349-1357. doi:10.1001/jama.2025.15440. PMID: 40878848; PMCID: PMC12397955.