Fr., 24.04.2026

AI-driven analysis of atrial fibrillation burden in pacemaker patients reveals no effect of AF burden on stroke

Press release

An analysis of the NOAH – AFNET 6 trial used large language models to extract AF burden from pacemaker data in patients with device-detected atrial fibrillation. This approach enables to evaluate the impact of AF burden on cardiovascular outcome and on the effectiveness and safety of anticoagulation in pacemaker patients. The AF burden in the population was 0.4%, with 20% of patients showing a baseline AF burden of more than 1%. In these patients, there was no effect of AF burden on stroke or other cardiovascular events. Today, the findings were presented by AFNET board member Prof. Ulrich Schotten, Maastricht, as a hotline at the Heart Rhythm congress 2026 in Chicago (1).

Patients with device-detected atrial fibrillation (DDAF) have a lower risk of stroke than patients with ECG-diagnosed atrial fibrillation (AF) and comparable stroke risk factors. AF burden – the amount of time a patient spends in AF – has emerged as an important factor linked to stroke risk and outcomes, yet it remains difficult to capture at scale in clinical research and practice.  

The primary analysis of NOAH – AFNET 6 (Non vitamin K antagonist Oral anticoagulants in patients with Atrial High-rate episodes), an investigator-initiated trial conducted by the AFNET, revealed: In patients with DDAF, anticoagulation slightly reduces the relatively low risk of stroke but also increases the risk of major bleeding. The trial was terminated early due to the expected increase in bleeding events in patients with DDAF while the stroke preventing effect was smaller than expected. The weak effects of anticoagulation were also found in several subgroups. (2-10)

This substudy of NOAH – AFNET 6 shows that AI-driven models using natural language processing can reliably automatically extract AF burden information from routine pacemaker reports supporting more individualized risk assessment and helping clinicians make more informed decisions about therapies such as anticoagulation. This approach was applied to NOAH – AFNET 6 to better understand how AF burden relates to clinical outcomes and response to the anticoagulant edoxaban.

Researchers analysed 11,964 pacemaker reports from 2,534 patients with device-detected AF enrolled in NOAH – AFNET 6. AF burden or mode switch burden was successfully identified in more than 70% of reports, demonstrating broad applicability to real-world data. The large language model-extracted AF burden was identical to manual review in more than 98% in a validation subcohort. In addition, AF burden and mode switch burden showed high concordance, reinforcing the reliability of device-based measures. Across the study population, baseline AF burden remained low, highlighting the importance of more precise measurement to better understand patient risk and treatment response.

The baseline AF burden was then correlated to cardiovascular events during 19 months median follow-up in the NOAH – AFNET 6 trial. Baseline AF burden did not modify thrombo-embolic risk, with low rates of stroke even in the small number of patients with a high AF burden. AF burden did not interact with the effectiveness of anticoagulation therapy in this detailed analysis. As expected, anticoagulation increased the risk of bleeding and death independent of AF burden.

“With atrial fibrillation on the rise worldwide, we must find better ways to leverage the latest technology to better understand not just whether patients have atrial fibrillation, but how much it affects them over time,” says Prof. Schotten, lead author and presenter of the data in Chicago. “This AI-driven large language model approach allows us to unlock meaningful insights from data we already collect and use them to advance research and improve patient care.”

“These results highlight the need to determine the effects of low-burden AF on stroke risk. The signal from this robust analysis is clear: A low AF burden translates into a low stroke risk. We need similar analyses in larger data sets to define which AF burden justifies anticoagulation therapy, and which burden requires rhythm control therapy. Together with international partners, we started to combine relevant data sets earlier this year (www.afburden.org)” states Paulus Kirchhof, the senior author of the analysis.

References

(1) Schotten U et al. Distribution of atrial fibrillation burden, relation to outcomes, and effectiveness and safety of anticoagulation based on device reports: The NOAH-AFNET 6 trial. 2026. HRS congress abstract

(2) Kirchhof P, Toennis T, Goette A, et al. Anticoagulation with Edoxaban in Patients with Atrial High-Rate Episodes. N Engl J Med 2023; 389:1167-1179. DOI:10.1056/NEJMoa2303062.

(3) Toennis T, Bertaglia E, Brandes A, et al. The influence of Atrial High Rate Episodes on Stroke and Cardiovascular Death – An update. Europace. 2023 Jul 4;25(7). DOI:10.1093/europace/euad166.

(4) Becher N, Toennis T, Bertaglia E, et al. Anticoagulation with edoxaban in patients with long Atrial High-Rate Episodes ≥24 hours. Eur Heart J. 2024 Mar 7;45(10):837-849. DOI:10.1093/eurheartj/ehad771

(5) Lip YH, Nikorowitsch J, Sehner S et al. Oral anticoagulation in device-detected atrial fibrillation: effects of age, sex, cardiovascular comorbidities, and kidney function on outcomes in the NOAH-AFNET 6 trial. Eur Heart J. 2024 April 9. DOI:10.1093/eurheartj/ehae225

(6) Diener HC, Becher N, Sehner S, Toennis T et al. Anticoagulation in patients with device-detected atrial fibrillation with and without a prior stroke or transient ischemic attack. The NOAH-AFNET 6 trial. J Am Heart Assoc. 2024 Sep 3;13(17):e036429. DOI:10.1161/JAHA.124.036429

(7) McIntyre WF, Benz AP, Becher N, et al. Direct Oral Anticoagulants for Stroke Prevention in Patients with Device-Detected Atrial Fibrillation: A Study-Level Meta-Analysis of the NOAH-AFNET 6 and ARTESiA Trials. Circulation. 2024 Mar 26;149(13):981-988. DOI:10.1161/CIRCULATIONAHA.123.067512

(8) Schnabel RB, Benezet-Mazuecos J, Becher N, McIntyre WF et al. Anticoagulation in patients with device-detected atrial fibrillation with and without concomitant vascular disease – A combined secondary analysis of the NOAH-AFNET 6 and ARTESiA trials. Eur Heart J. 2024 Dec 7;45(46):4902-4916. DOI:10.1093/eurheartj/ehae596

(9) Becher N, Koellner G, Blomstrom-Lundqvist C, Camm AJ et al. Effects of anticoagulation in patients with device-detected atrial fibrillation and multiple stroke risk factors: A Win Ratio analysis of the NOAH-AFNET 6 trial. Eur Heart J Qual Care Clin Outcomes. 2025 Dec 19;11(8):1351-1358. DOI:10.1093/ehjqcco/qcaf087

(10) Goette A, Lemoine MD, Fierenz A et al. Kidney disease increases the risk of cardiovascular events in patients with device-detected atrial fibrillation: NOAH-AFNET 6. Europace. 2026. DOI:10.1093/europace/euag083

About the Atrial Fibrillation NETwork (AFNET)

The Atrial Fibrillation NETwork is an interdisciplinary research network comprising scientists and physicians from hospitals and practices dedicated to improving the management of atrial fibrillation through coordinated research in Germany, Europe, and worldwide. Its main objective is to conduct high quality investigator-initiated clinical trials and registries on a national and international level as well as translational research projects. The AFNET continues the long-term activities of the network which has been funded by the German Federal Ministry of Research and Education over a decade. Since January 2015, specific projects and infrastructures of the AFNET are funded by the German Centre for Cardiovascular Research (DZHK), and some projects by EU research grants. AFNET has long expertise in the management of atrial fibrillation, but also provides support for work in other fields informing cardiovascular care. The results of 20 years of clinical and translational research improved the lives of patients with cardiovascular diseases and influenced treatment guidelines.

https://www.af-net.eu

Funding of the NOAH trial: AFNET, DZHK, Daiichi Sankyo. This analysis was partially funded by the European Union AF-B-STEP (grant agreement 101252780, www.afburden.org).

NOAH registration: NCT 02618577, ISRCTN 17309850

Press Contact

Angelika Leute, PhD
Phone: +49 202 2623395
a.leute@t-online.de

Mo., 13.04.2026

Kidney disease increases the risk of cardiovascular events in patients with device-detected atrial fibrillation

Press release

A prespecified analysis of the NOAH – AFNET 6 trial investigated the impact of kidney function on cardiovascular outcome in patients with device-detected atrial fibrillation. Today, the findings were presented by AFNET board member Prof. Andreas Goette, St. Vincenz Hospital, Paderborn, Germany, at the annual congress of the European Heart Rhythm Association (EHRA) in Paris and published in the EP Europace journal (1,2).

Patients with device-detected atrial fibrillation (DDAF) have a lower risk of stroke than patients with ECG-diagnosed atrial fibrillation (AF) and comparable stroke risk factors. Reduced kidney function is associated with higher rates of stroke and cardiovascular events in patients with AF. Whether chronic kidney disease (CKD) affects the cardiovascular treatment effects of anticoagulation in patients with DDAF is still an open question.

NOAH – AFNET 6 (Non vitamin K antagonist Oral anticoagulants in patients with Atrial High-rate episodes), an investigator-initiated trial conducted by the AFNET, was terminated early due to the expected increase in bleeding events in patients with DDAF while the stroke preventing effect was smaller than expected. The main trial found that patients with DDAF have a low risk of stroke without anticoagulation. Oral anticoagulation slightly reduces the risk of stroke further but also increases the
risk of major bleeding. The weak effects of anticoagulation were also found in several subgroups. (3-10)

Kidney disease has been suggested as a marker for an increased stroke risk in patients with AF. This prespecified NOAH – AFNET 6 analysis compared anticoagulation with edoxaban treatment with no anticoagulation in 2534 patients with DDAF at various stages of chronic kidney disease defined according to the 2024 Kidney Disease Improving Global Outcomes (KDIGO) criteria.

Primary outcome events (a composite of stroke, systemic embolism, or cardiovascular death) increased with increasing severity of CKD, which was driven by higher rates of cardiovascular death and systemic embolic events. Total stroke rate was low across all CKD stages. Safety events (major bleeding or death) also increased with increasing severity of CKD, with more major bleeding than death.

Prof. Goette explained: “Our analysis showed that age and kidney function are the strongest predictors of cardiovascular events, in particular cardiovascular death, in patients with DDAF and clinical stroke risk factors. The results also demonstrate that the approved dose of edoxaban retains its effectiveness across the spectrum of kidney functions tested.”

Prof. Paulus Kirchhof, AFNET board chair and principal investigator of the NOAH – AFNET 6 trial, stated: “This exploratory analysis suggests that the estimated glomerular filtration rate (eGFR), a widely available blood biomarker, could be useful to refine thromboembolic risk estimation in patients with DDAF and reduced kidney function in context with AF burden. Clearly, the findings call for independent, external validation in contemporary patients with DDAF.”

References

(1) Goette A et al. Kidney disease increases the risk of cardiovascular events in patients with device-detected atrial fibrillation: NOAH-AFNET 6. Abstract beim EHRA Kongress 2026

(2) Goette A, Lemoine MD, Fierenz A et al. Kidney disease increases the risk of cardiovascular events in patients with device-detected atrial fibrillation: NOAH-AFNET 6. Europace. 2026. DOI:10.1093/europace/euag083

(3) Kirchhof P, Toennis T, Goette A, et al. Anticoagulation with Edoxaban in Patients with Atrial High-Rate Episodes. N Engl J Med 2023; 389:1167-1179. DOI:10.1056/NEJMoa2303062.

(4) Toennis T, Bertaglia E, Brandes A, et al. The influence of Atrial High Rate Episodes on Stroke and Cardiovascular Death – An update. Europace. 2023 Jul 4;25(7). DOI:10.1093/europace/euad166.

(5) Becher N, Toennis T, Bertaglia E, et al. Anticoagulation with edoxaban in patients with long Atrial High-Rate Episodes ≥24 hours. Eur Heart J. 2024 Mar 7;45(10):837-849. DOI:10.1093/eurheartj/ehad771

(6) Lip YH, Nikorowitsch J, Sehner S et al. Oral anticoagulation in device-detected atrial fibrillation: effects of age, sex, cardiovascular comorbidities, and kidney function on outcomes in the NOAH-AFNET 6 trial. Eur Heart J. 2024 April 9. DOI:10.1093/eurheartj/ehae225

(7) Diener HC, Becher N, Sehner S, Toennis T et al. Anticoagulation in patients with device-detected atrial fibrillation with and without a prior stroke or transient ischemic attack. The NOAH-AFNET 6 trial. J Am Heart Assoc. 2024 Sep 3;13(17):e036429. DOI:10.1161/JAHA.124.036429

(8) McIntyre WF, Benz AP, Becher N, et al. Direct Oral Anticoagulants for Stroke Prevention in Patients with Device-Detected Atrial Fibrillation: A Study-Level Meta-Analysis of the NOAH-AFNET 6 and ARTESiA Trials. Circulation. 2024 Mar 26;149(13):981-988. DOI:10.1161/CIRCULATIONAHA.123.067512

(9) Schnabel RB, Benezet-Mazuecos J, Becher N, McIntyre WF et al. Anticoagulation in patients with device-detected atrial fibrillation with and without concomitant vascular disease – A combined secondary analysis of the NOAH-AFNET 6 and ARTESiA trials. Eur Heart J. 2024 Dec 7;45(46):4902-4916. DOI:10.1093/eurheartj/ehae596

(10) Becher N, Koellner G, Blomstrom-Lundqvist C, Camm AJ et al. Effects of anticoagulation in patients with device-detected atrial fibrillation and multiple stroke risk factors: A Win Ratio analysis of the NOAH-AFNET 6 trial. Eur Heart J Qual Care Clin Outcomes. 2025 Dec 19;11(8):1351-1358. DOI:10.1093/ehjqcco/qcaf087

About the Atrial Fibrillation NETwork (AFNET)

The Atrial Fibrillation NETwork is an interdisciplinary research network comprising scientists and physicians from hospitals and practices dedicated to improving the management of atrial fibrillation through coordinated research in Germany, Europe, and worldwide. Its main objective is to conduct high quality investigator-initiated clinical trials and registries on a national and international level as well as translational research projects. The AFNET continues the long-term activities of the network which has been funded by the German Federal Ministry of Research and Education over a decade. Since January 2015, specific projects and infrastructures of the AFNET are funded by the German Centre for Cardiovascular Research (DZHK), and some projects by EU research grants. AFNET has long expertise in the management of atrial fibrillation, but also provides support for work in other fields informing cardiovascular care. The results of 20 years of clinical and translational research improved the lives of patients with cardiovascular diseases and influenced treatment guidelines.

https://www.af-net.eu

Funding of the NOAH trial: AFNET, DZHK, Daiichi Sankyo

NOAH registration: NCT 02618577, ISRCTN 17309850

Press Contact

Angelika Leute, PhD
Phone: +49 202 2623395
a.leute@t-online.de

Fr., 20.02.2026

Digital Impulses: Detecting Heart Disease via Smartphone

Can smartphones play a decisive role in advancing personalized cardiology? In the interview series “Digital Impulses,” Larissa Fabritz from the University Heart and Vascular Center Hamburg discusses the possibilities of early cardiological detection using smartphones.

The focus is on applications for detecting atrial fibrillation or heart attacks, as well as the question of how digital technologies can be made practical and independently usable in everyday life – including for older adults.

You can watch the video here (duration: 8 minutes, german only):

Digitalimpulse: Erkennung von Herzerkrankungen per Smartphone

Wed., 4.02.2026

AF-B STEP: Global collaboration to reduce the burden of atrial fibrillation and advance quantification and treatment

Press release

The project will develop uniform standards for how medical devices and consumer technologies from implantable monitors to smartwatches detect and quantify AF and its burden.

Eighteen partners from Europe and Canada have joined forces in this initiative with the aim of fundamentally improving the diagnosis and care of people with AF. AFNET is one of these partners.

New international research project AF-B-STEP will for the first time systematically assess how much time individuals spend in atrial fibrillation (AF) — their AF burden — and determine how this burden affects risks such as stroke, heart failure, and overall quality of life.

Atrial fibrillation (AF) affects millions of people worldwide – yet the condition is rarely quantified upon diagnosis. The international research project AF-B-STEP aims to change this: for the first time, it will systematically assess how much time individuals spend in AF, expressed as their AF burden, and determine the extent to which the AF burden influences the risk of stroke, heart failure and other aspects of patients´ lives. Furthermore, the project will develop uniform standards for how medical devices (such as cardiac implantable devices or insertable cardiac monitors) and consumer electronics (e.g., smartwatches) quantify AF and its burden. The goal is to fundamentally improve the diagnosis and care of people with AF. 18 partners across Europe and Canada from academia and industry have joined forces for this project, coordinated by the Department of Cardiology at the University Heart and Vascular Center of the University Medical Center Hamburg-Eppendorf (UKE) in Hamburg, Germany, and by the Medtronic Bakken Research Center in Maastricht, The Netherlands, as industry lead. The project will be funded over the next four years with a total of approximately 18 million euros by the Innovative Health Initiative (IHI) with contributions from both the European Union and industry.

“The results are intended to help physicians make more precise decisions about who needs which treatment based on the AF burden. The goal of AF-B-STEP is to contribute to a measurable reduction in strokes and heart failure in the long term, while simultaneously avoiding unnecessary treatments in people with a low atrial fibrillation burden,” says Prof. Dr. Paulus Kirchhof, Director of the Department of Cardiology at the University Medical Center Hamburg-Eppendorf (UKE), AFNET board chair, and coordinator of the AF-B-STEP project (full project title: Quantifying Atrial Fibrillation Burden for Better Screening, Treatment, and HEalth Policy).

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia worldwide and increases the risk of stroke and heart failure. It affects about one-third of people over the age of 55 and accounts for two to three percent of healthcare costs in Europe and North America. Currently, AF is usually diagnosed simply with “yes” or “no,” an therapeutic decisions are also predominantly based on this simple classification. However, patients experience many different patterns and intensities of AF: from rare, short episodes to frequent episodes and chronic forms when AF is present all of the time. The time in AF, the so-called AF burden, has an important impact on symptoms, prognosis, and therapeutic decisions. The risk of stroke, heart failure, hospital admissions and other adverse outcomes increases with a higher AF burden. Implantable cardiac devices and, increasingly, smartwatches, fitness trackers, and other wearable technologies now allow even short and infrequent episodes to be detected. However, a standardised method for accurately quantifying AF burden and precisely assessing the resulting health risks is still lacking. Furthermore, the data collected by implanted and wearable devices are not reported uniformly, which complicates comparisons between different systems.

Analysis of data from more than 100,000 patients worldwide

This is the starting point of AF-B-STEP, which initially compiles and analyzes existing data on AF burden and its health consequences. For this purpose, consortium partners from academia and industry are providing anonymised data from more than 100,000 patients. By linking AF burden with clinical outcomes, it should be possible to precisely calculate its contribution to stroke, heart failure, and cardiovascular death, as well as how AF affects quality of life as well as cardiac and brain function. Together with manufacturers of implantable cardiac devices and wearable technologies, the consortium will also develop standardised methods for recording and displaying AF burden to affected individuals. Ideally, three categories will emerge: low AF burden (no further investigations or therapies required), moderate AF burden (further diagnostics necessary for treatment decisions), and high AF burden (immediate initiation of anticoagulation and rhythm control therapy). Better patient stratification and mechanistic results can then inform future treatment guidelines and strengthen the role of AF burden in treatment decisions.

“By addressing the unmet needs in atrial fibrillation management, this large concerted collaboration will be foundational to help guide future efforts to improve the management of AF globally,” said Dr. Mirko De Melis, Distinguished Clinical Research Advisor at Medtronic Bakken Research Center in Maastricht, The Netherlands and Industry Lead of the AF-B-STEP project.

“While atrial fibrillation burden is widely discussed, its clinical application remains limited by the absence of validated thresholds. AF-B-STEP will address this gap by uniting exceptional datasets, experienced investigators, and industry collaborators to enable the practical use of AF burden in clinical care,” said Dr. William McIntyre, project lead and scientist at the Population Health Research Institute, a joint institute of McMaster University and Hamilton Health Sciences.

Prof. Dr. Barbara Casadei, Head of the National Heart and Lung Institute at Imperial College London, UK, said: “Atrial fibrillation is a major global health concern, and the numbers – in the millions – continue to increase every year. This project is a landmark opportunity for researchers, scientists and clinicians to seize the initiative and find the best ways to assess, risk-stratify and manage people with the condition. We hope and believe that in four years’ time we will be embarking on a significant step
change in the diagnosis and care of atrial fibrillation.”

“For too long, atrial fibrillation has been treated as a simple ‘yes or no’ condition. AF-B-STEP has the potential to change clinical practice by linking AF burden to meaningful outcomes such as stroke and heart failure, ultimately improving care for millions of patients worldwide,” says Prof. Dr. Helmut Pürerfellner, President of the European Heart Rhythm Association (EHRA), an AF-B-STEP partner and a branch of the European Society of Cardiology.

“At BIOTRONIK, we believe that clear, consistent standards for reporting are essential to effectively researching atrial fibrillation burden and ultimately improving patient care. Through our data and scientific expertise, we support the AF-B-STEP project in developing definitions and methodologies that can be broadly applied,” said Dr. Volker Lang, Senior Vice President Research & Development at BIOTRONIK.

“The magnitude, scope and strength of this academic – industry collaboration promises to deliver not only a standardized framework to measure and quantify atrial fibrillation burden, but importantly to link AF burden to serious outcomes. Understanding this relationship between AF burden and outcomes is key to defining clinically meaningful endpoints for future development of much needed treatments in this growing area of disease risk and population burden,” said Dr. Amy Sehnert from
Thryv Therapeutics Inc.

International Consortium

AF-B-STEP is an international research project bringing together university medical centres, industry representatives from the medical device, pharmaceutical, and digital health sectors, international cardiology organisations, patient groups, management and dissemination professionals, and healthcare payers from Europe and Canada.

The partners include:

Kick-off Meeting

The AF-B-STEP Consortium convenes for the first time in Amsterdam, The Netherlands, from 3rd-5th February. The kick-off meeting is intended to motivate the team to coordinate and streamline the work with dedication and a clear purpose – to reduce the global burden of AF and advance its quantification and treatment.

Funding

This project is supported by the Innovative Health Initiative Joint Undertaking (IHI JU) under grant agreement No 101252780. The JU receives support from the European Union’s Horizon Europe research and innovation programme, COCIR, EFPIA, EuropaBio, MedTech Europe, Vaccines Europe, and from consortium partners Acesion Pharma ApS, Medical Algorithmics, Preventicus GmbH, Thryv Therapeutics Inc., and Withings. Views and opinions expressed are those of the author(s) only and do not necessarily reflect those of the aforementioned parties. Neither of the aforementioned parties can be held responsible for them.

For more information

For more information on AF-B-STEP, please visit https://afbstep.eu/ or any of the project’s social
media channels: LinkedIn, BlueSky or X. You can also contact the project via email: info@afbstep.eu

About the Atrial Fibrillation NETwork (AFNET)

The Atrial Fibrillation NETwork is an interdisciplinary research network comprising scientists and physicians from hospitals and practices dedicated to improving the management of atrial fibrillation through coordinated research in Germany, Europe, and worldwide. Its main objective is to conduct high quality investigator-initiated clinical trials and registries on a national and international level as well as translational research projects. The AFNET continues the long-term activities of the network which has been funded by the German Federal Ministry of Research and Education over a decade. Since January 2015, specific projects and infrastructures of the AFNET are funded by the German Centre for Cardiovascular Research (DZHK), and some projects by EU research grants. AFNET has long expertise in the management of atrial fibrillation, but also provides support for work in other fields informing cardiovascular care. The results of 20 years of clinical and translational research improved the lives of patients with cardiovascular diseases and influenced treatment guidelines.

https://www.af-net.eu

Press Contact

Angelika Leute, PhD
Phone: +49 202 2623395
a.leute@t-online.de

We, 07.01.2026

Transforming Atrial Fibrillation Management by Targeting Comorbidities and Reducing Atrial Fibrillation Burden – an AFNET/EHRA position paper

Press release

An international panel of experts published recommendations to improve care of atrial fibrillation patients. The paper summarizes the results of the 10th AFNET/EHRA consensus conference – a two-day meeting of more than 80 renowned experts from academia and industry in May 2025 which was jointly organized by the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA). On 15 December 2025, the consensus report was published in the EP Europace journal (1).

Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with stroke, heart failure, and other severe complications. It affects several million people worldwide and is a growing unmet medical need in an aging population.

During the 10th AFNET/EHRA consensus conference the invited scientists pooled their interdisciplinary knowledge on AF management and research and discussed new perspectives for better care. They identified knowledge gaps and key research priorities. The essence of their discussions is summarized in this consensus report.

Dr. Emma Svennberg, cardiologist from Stockholm, Sweden, and first author of the consensus paper, explained: “AF treatment is undergoing considerable shift from an exclusive focus on stroke prevention to management of concomitant co-morbidities and AF burden reduction. However, both rhythm control and therapy of coexisting conditions remain underused, and patients with AF continue to experience poor outcomes with associated high healthcare costs. This underscores the need for streamlined treatment to target risk factors, AF burden and rhythm.”

Prof. Paulus Kirchhof, Hamburg, Germany, AFNET board chair and one of the four chairpersons of the consensus conference, stated: “The growing role of rhythm control as a treatment with the potential to modify the disease trajectory by reducing AF burden and to reduce cardiovascular events creates a new unmet need for simple, safe, and effective rhythm control therapies. While catheter ablation continues to expand, many patients with AF will require pharmacological rhythm control therapy, either as a primary or adjunctive approach. Development of new antiarrhythmic drugs, optimizing the use of existing antiarrhythmic drugs and new methods to prevent AF remain clinical imperatives.”

The consensus report furthermore describes quantitative traits that may enable a shift towards risk-driven therapy strategies that are safe, accessible, and patient-centred. Applying artificial intelligence methods can further improve risk estimation and personalized therapy selection.

Prof. Andreas Goette, Paderborn, Germany, AFNET board member and co-chair of the consensus conference, concluded: “Together, these efforts offer pathways towards personalized, patient-centred, multimodal and accessible AF management that integrates rhythm control, stroke prevention, and therapy of concomitant conditions to bridge today’s practical needs with tomorrow’s therapeutic innovation.”

Prof. Jose Luis Merino, Madrid, Spain, past-president of EHRA and co-chair of the 10th AFNET/EHRA consensus conference, said: “For many years, the AFNET/EHRA consensus conferences have been an important forum for international cooperation among recognized experts in the field of atrial fibrillation. We believe that the recommendations of this expert panel will help to optimize AF therapy and improve the outcomes of many AF patients in the world.”

Participants of the 10th AFNET/EHRA Consensus Conference came from Europe, USA, Canada, and Australia. The meeting was chaired by the four cardiologists Prof. Andreas Goette and Prof. Paulus Kirchhof, both from AFNET, and Dr. Emma Svennberg and Prof. Jose Luis Merino, both from EHRA.

The conference was organized by AFNET and EHRA with financial support from MAESTRIA which is funded under European Union’s (EU) Horizon 2020 research and innovation program (grant number 965286). Industry participants paid an attendance fee.

References

(1) Svennberg E et al. Transforming Atrial Fibrillation Management by Targeting Comorbidities and Reducing Atrial Fibrillation Burden: the 10th AFNET/EHRA Consensus Conference. Europace, 15.Dez 2025. DOI: 10.1093/europace/euaf318

About the Atrial Fibrillation NETwork (AFNET)

The Atrial Fibrillation NETwork is an interdisciplinary research network comprising scientists and physicians from hospitals and practices dedicated to improving the management of atrial fibrillation through coordinated research in Germany, Europe, and worldwide. Its main objective is to conduct high quality investigator-initiated clinical trials and registries on a national and international level as well as translational research projects. The AFNET continues the long-term activities of the network which has been funded by the German Federal Ministry of Research and Education over a decade. Since January 2015, specific projects and infrastructures of the AFNET are funded by the German Centre for Cardiovascular Research (DZHK), and some projects by EU research grants. AFNET has long expertise in the management of atrial fibrillation, but also provides support for work in other fields informing cardiovascular care. The results of 20 years of clinical and translational research improved the lives of patients with cardiovascular diseases and influenced treatment guidelines.

Press Contact

Angelika Leute, PhD
Tel: 0202 2623395
a.leute@t-online.de

Mo, 01.09.2025

AF burden on early rhythm control modulates patient outcomes

Press Release

An analysis of patient-operated ECGs from the EAST – AFNET 4 trial revealed: A low AF burden below 6% in the first year of early rhythm control therapy was associated with low cardiovascular event rates during the subsequent 4 years of follow-up. Patients with a higher AF burden on early rhythm control suffered more AF-related events. Today the findings were presented by AFNET board member Prof. Ulrich Schotten, Maastricht University, in a hotline session at the annual congress of the European Society of Cardiology (ESC) in Madrid (1,2).

Atrial fibrillation (AF) is a common arrhythmia leading to severe complications including stroke, heart failure and cardiovascular death. Currently AF is diagnosed by ECG, creating a lifelong, binary diagnosis based on presence of a single ECG showing AF. Recent data illustrated the shortcomings of this binary diagnosis and suggest that AF burden as a quantitative parameter, defined as the time spent in AF per monitored time, better reflects disease severity and modulates the risk of stroke and other cardiovascular events (3,4).

Prof. Schotten explained: “Intermittent monitoring using patient-operated ECGs or wearables enables estimates of AF burden that could refine the diagnosis and enable individualised therapy. If AF burden estimated by patient-operated ECGs were related to cardiovascular outcomes, this would invite their use for remote, digital patient management. To investigate this question, we analysed ECG data from the EAST – AFNET 4 trial.”  

The EAST – AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention) trial demonstrated that early rhythm control – with antiarrhythmic drugs or atrial fibrillation ablation – delivered within one year after AF diagnosis improves outcomes compared to usual care (UC) over a 5-year follow-up time (5). A series of sub-analyses of the EAST – AFNET 4 data set verified the results for different sub-groups (6-17).

In the present analysis, AF burden was estimated using artificial-intelligence-based rhythm classification of patient-operated telemetric ECGs in patients randomised to early rhythm control in the EAST – AFNET 4 trial.

1,178 patients (70 years, 47% women, CHA2DS2-VA 2·8±1·2) transmitted 303,308 ECGs over 5.1 years. Median AF burden was 6% in the first year of follow-up. AF burden below the median was associated with low rates of cardiovascular death, stroke, or unplanned hospitalisation for heart failure or acute coronary syndrome. An AF burden above the median was associated with higher event rates, comparable to events with usual care.

Prof. Schotten concluded: “Our findings suggest that AF burden, estimated from patient-operated ECGs, is linked to AF-related events on rhythm control therapy. They call for further exploration of the role of AF burden and AF burden reduction for personalised rhythm-control therapy in patients with AF.”

References

(1) Zeemering S, Borof K, Schotten U, Obergassel J, Camm AJ, Crijns HJGM, Eckardt L, Fabritz L, Goette A, Habibi Z, Hermans BJM, Lemoine MD, Magnussen C, Metzner A, Rillig A, Schnabel RB, Suling A, Vardas P, Willems S, Zapf A, Kirchhof P. Atrial fibrillation burden on early rhythm-control and cardiovascular events in the EAST-AFNET 4 AF trial. Abstract ESC Congress 2025

(2) Zeemering S, Borof K, Schotten U, Obergassel J, Camm AJ, Crijns HJGM, Eckardt L, Fabritz L, Goette A, Habibi Z, Hermans BJM, Lemoine MD, Magnussen C, Metzner A, Rillig A, Schnabel RB, Suling A, Vardas P, Willems S, Zapf A, Kirchhof P. Estimated atrial fibrillation burden on early rhythm-control and cardiovascular events in the EAST-AFNET 4 trial. EClinicalMedicine. 2025 Sep 01. DOI:10.1016/j.eclinm.2025.103457

(3) Linz D, Andrade JG, Arbelo E, Boriani G, Breithardt G, Camm AJ, Caso V, Nielsen JC, De Melis M, De Potter T, Dichtl W, Diederichsen SZ, Dobrev D, Doll N, Duncker D, Dworatzek E, Eckardt L, Eisert C, Fabritz L, Farkowski M, Filgueiras-Rama D, Goette A, Guasch E, Hack G, Hatem S, Haeusler KG, Healey JS, Heidbuechel H, Hijazi Z, Hofmeister LH, Hove-Madsen L, Huebner T, Kaab S, Kotecha D, Malaczynska-Rajpold K, Merino JL, Metzner A, Mont L, Ng GA, Oeff M, Parwani AS, Puererfellner H, Ravens U, Rienstra M, Sanders P, Scherr D, Schnabel R, Schotten U, Sohns C, Steinbeck G, Steven D, Toennis T, Tzeis S, van Gelder IC, van Leerdam RH, Vernooy K, Wadhwa M, Wakili R, Willems S, Witt H, Zeemering S, Kirchhof P. Longer and better lives for patients with atrial fibrillation: the 9th AFNET/EHRA consensus conference. Europace. 2024 Mar 30;26(4) DOI:10.1093/europace/euae070

(4) Becher N, Metzner A, Toennis T, Kirchhof P, Schnabel RB. Atrial fibrillation burden: a new outcome predictor and therapeutic target. Eur Heart J. 2024 Aug 16;45(31):2824-2838. DOI:10.1093/eurheartj/ehae373

(5) Kirchhof P, Camm AJ, Goette A, Brandes A, Eckardt L, Elvan A, Fetsch T, van Gelder IC, Haase D, Haegeli LM, Hamann F, Heidbüchel H, Hindricks G, Kautzner J, Kuck K-H, Mont L, Ng GA, Rekosz J, Schön N, Schotten U, Suling A, Taggeselle J, Themistoclakis S, Vettorazzi E, Vardas P, Wegscheider K, Willems S, Crijns HJGM, Breithardt G, for the EAST–AFNET 4 trial investigators. Early rhythm control therapy in patients with atrial fibrillation. N Engl J Med. 2020; 383:1305-1316. DOI:10.1056/NEJMoa2019422

(6) Metzner A, Suling A, Brandes A, Breithardt G, Camm AJ, Crijns HJGM, Eckardt L, Elvan A, Goette A, Haegeli LM, Heidbuchel H, Kautzner J, Kuck KH, Mont L, Ng GA, Szumowski L, Themistoclakis S, van Gelder IC, Vardas P, Wegscheider K, Willems S, Kirchhof P. Anticoagulation, therapy of concomitant conditions, and early rhythm control therapy: a detailed analysis of treatment patterns in the EAST – AFNET 4 trial. EP Europace. 2022; 24:552–564. DOI:10.1093/europace/euab200

(7) Rillig A, Magnussen C, Ozga, Suling A, Brandes A, Breithardt G, Camm AJ, Crijns HJGM, Eckardt L, Elvan A, Goette A, Gulizia M, Haegeli LM, Heidbuchel H, Kuck KH, Ng GA, Szumowski L, van Gelder IC, Wegscheider K, Kirchhof P. Early rhythm control therapy in patients with heart failure. Circulation. 2021;144(11):845-858. DOI:10.1161/CIRCULATIONAHA.121.056323

(8) Willems S, Borof K, Brandes A, Breithardt G, Camm AJ, Crijns HJGM, Eckardt L, Gessler N, Goette A, Haegeli LM, Heidbuchel H, Kautzner J, Ng GA, Schnabel R, Suling A, Szumowski L, Themistoclakis S, Vardas P, van Gelder IC, Wegscheider K, Kirchhof P. Systematic, early rhythm control therapy equally improves outcomes in asymptomatic and symptomatic patients with atrial fibrillation: the EAST-AFNET 4 Trial. Eur Heart J. 2022; 43:1219-1230. DOI:10.1093/eurheartj/ehab593.

(9) Goette a, Borof K, Breithardt G, Camm AJ, Crijns H, Kuck KH, Wegscheider K, Kirchhof P, MD. Presenting Pattern of Atrial Fibrillation and Outcomes of Early Rhythm Control Therapy. J Am Coll Cardiol. 2022; 80:283-95. DOI:10.1016/j.jacc.2022.04.058

(10) Rillig A, Borof K, Breithardt G, Camm AJ, Crijns HJGM, Goette A, Kuck KH, Metzner A, Vardas P, Vettorazzi E, Wegscheider K, Zapf A, Kirchhof P. Early rhythm control in patients with atrial fibrillation and high comorbidity burden. Circulation. 2022 Sep 13;146(11):836-847. DOI:10.1161/CIRCULATIONAHA.122.060274

(11) Jensen M, Suling A, Metzner A, Schnabel R, Borof K, Goette A, Haeusler KG, Zapf A, Wegscheider K, Fabritz L, Diener H-C, Thomalla G, Kirchhof P. Early rhythm-control therapy for atrial fibrillation in patients with a history of stroke: a subgroup analysis of the EAST- AFNET 4 trial. Lancet Neurol. 2023; 22: 45–54. DOI:10.1016/PIIS1474-4422(22)00436-7 

(12) Eckardt L, Sehner S, Suling A, Borof K, Breithardt G, Crijns HJGM, Goette A, Wegscheider K, Zapf A, Camm AJ, Metzner A, Kirchhof P. Attaining sinus rhythm mediates improved outcome with early rhythm control therapy of atrial fibrillation: the EAST – AFNET 4 trial. Eur Heart J. 2022 Oct 21;43(40):4127-4144. DOI:10.1093/eurheartj/ehac471

(13) Van Gelder IC, Ekrami NK, Borof K, Fetsch T, Magnussen C, Mulder BA, Schnabel R, Wegscheider K, Rienstra M, Kirchhof P; EAST-AFNET 4 Trial Investigators. Sex Differences in Early Rhythm Control of Atrial Fibrillation in the EAST-AFNET 4 Trial. J Am Coll Cardiol. 2023 Feb 28;81(8):845-847. DOI:10.1016/j.jacc.2022.12.011.

(14) Gottschalk S, Kany S, König H-H, Crijns HJGM, Vardas P, Camm AJ, Wegscheider K, Metzner A, Rillig A, Kirchhof P, Dams J. Cost- effectiveness of early rhythm-control versus usual care in atrial fibrillation care: an analysis based on the German subsample of the EAST-AFNET 4 trial. EP Europace. 2023 May 19;25(5). DOI:10.1093/europace/euad051

(15) Kany S, Al-Taie C, Roselli C, Pirruccello JP, Borof K, Reinbold C, Suling A, Krause L, Reissmann B, Schnabel R, Zeller T, Zapf A, Wegscheider K, Fabritz L, Ellinor PT, Kirchhof P. Association of genetic risk and outcomes in patients with early rhythm control therapy in atrial fibrillation: results from the EAST-AFNET4 study. Cardiovasc Res. 2023 Aug 7;119(9):1799-1810. DOI:10.1093/cvr/cvad027

(16) Fabritz L, Chua W, Cardoso VR, Al-Taie C, Borof K, Suling A, Krause L, Kany S, Magnussen C, Wegscheider K, Breithardt G, Crijns HJGM, Camm AJ, Gkoutos G, Ellinor PT, Goette A, Schotten U, Wienhues-Thelen U-H, Zeller T, Schnabel RB, Zapf A, Kirchhof P. Blood-based cardiometabolic phenotypes in atrial fibrillation and their associated risk: EAST-AFNET 4 biomolecule study. Cardiovasc Res. 2024. DOI:10.1093/cvr/cvae067

(17) Fabritz L, Al-Taie C, Borof K, Breithardt G, Camm J, Crijns HJGM, Cardoso VR, Chua W, van Elferen S, Eckardt L, Gkoutos G, Goette A, Guasch E, Hatem S, Metzner A, Mont L, Murukutla AV, Obergassel J, Rillig A, Sinner MF, Schnabel RB, Schotten U, Sommerfeld LC, Wienhues-Thelen U-H, Zapf A, Zeller T, Kirchhof P. Biomarker-based prediction of sinus rhythm in atrial fibrillation patients: the EAST-AFNET4 biomolecule study. Eur Heart J. 2024 Dec 14;45(47):5002-19. DOI:10.1093/eurheartj/ehae611

About the EAST – AFNET 4 trial

EAST – AFNET 4 is an investigator-initiated trial (IIT) that compared two different treatment strategies in atrial fibrillation. The EAST – AFNET 4 trial tested whether an early, comprehensive rhythm control therapy can prevent adverse cardiovascular outcomes in patients with atrial fibrillation (AF) compared to usual care.

A total of 2789 patients with early AF (diagnosed less than a year ago) and at least two cardiovascular conditions (approximating a CHA₂DS₂-VASc score >=2) were enrolled by 135 sites in 11 countries during 2011 to 2016. Patients were randomized 1:1 to early rhythm control therapy or usual care, stratified by sites. Patients in both groups received guideline-recommended treatment for underlying cardiovascular conditions, anticoagulation, and rate control.

All patients in the early rhythm control group received antiarrhythmic drugs or catheter ablation after randomization (chosen by the local study teams). Rhythm control therapy was escalated with AF ablation and/or antiarrhythmic drugs when recurrent AF was documented clinically or by ECG, including monitoring with patient-operated ECG devices.

Patients in the usual care group were initially managed with rate control. Rhythm control therapy was only used to improve atrial fibrillation-related symptoms despite optimal rate control, following current guidelines.

About the Atrial Fibrillation NETwork (AFNET)

The Atrial Fibrillation NETwork is an interdisciplinary research network comprising scientists and physicians from hospitals and practices dedicated to improving the management of atrial fibrillation through coordinated research in Germany, Europe, and worldwide. Its main objective is to conduct high quality investigator-initiated clinical trials and registries on a national and international level as well as translational research projects. The AFNET continues the long-term activities of the network which has been funded by the German Federal Ministry of Research and Education over a decade. Since January 2015, specific projects and infrastructures of the AFNET are funded by the German Centre for Cardiovascular Research (DZHK), and some projects by EU research grants. AFNET has long expertise in the management of atrial fibrillation, but also provides support for work in other fields informing cardiovascular care. The results of 20 years of clinical and translational research improved the lives of patients with cardiovascular diseases and influenced treatment guidelines.

www.kompetenznetz-vorhofflimmern.de

Funding: AFNET, BMBF, DZHK, EHRA, Deutsche Herzstiftung, Abbott, Sanofi

Mo, 01.09.2025

Anticoagulation in patients with device-detected atrial fibrillation remains individual decision

Press Release

A Win Ratio analysis confirmed the primary result of the NOAH – AFNET 6 trial and did not find an advantage of anticoagulation with edoxaban over no anticoagulation in patients with device-detected atrial fibrillation. Clinical decisions should therefore be guided by individual factors. The findings were presented by Dr. Nina Becher, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany, in a hotline session at the annual congress of the European Society of Cardiology (ESC) in Madrid. (1,2)

Patients with device-detected atrial fibrillation (DDAF) have a lower risk of stroke than patients with ECG-diagnosed atrial fibrillation (AF) and comparable stroke risk factors. Which of the patients with DDAF need anticoagulation for stroke prevention is still an open question.

The primary analysis of NOAH – AFNET 6 (Non vitamin K antagonist Oral anticoagulants in patients with Atrial High-rate episodes), an investigator-initiated trial conducted by the AFNET, revealed: In patients with DDAF, anticoagulation slightly reduces the relatively low risk of stroke but also increases the risk of major bleeding. The trial was terminated early due to the expected increase in bleeding events in patients with DDAF while the stroke preventing effect was smaller than expected. The weak effects of anticoagulation were also found in several subgroups. (3-9)

Dr. Becher explained: “Some of the events summarized in the combined study endpoint of NOAH – AFNET 6 have a higher impact on patients´ lives than others. Death is more severe than bleeding. Therefore we performed a win ratio analysis. This statistical method prioritises events in a hierarchical order based on their clinical importance and thereby provides a nuanced assessment of the benefit of oral anticoagulation in patients with DDAF and stroke risk factors.”

The win ratio analysis included a total of 2,534 patients who participated in the NOAH – AFNET 6 trial. The components of the primary composite were used in the following hierarchical order: (1) overall death, (2) stroke, (3) systemic embolism, myocardial infarction or pulmonary embolism, and (4) major bleeding. In addition, win odds were also calculated as a measure that accounts for the number of undecided comparisons between anticoagulant and placebo. Dr. Becher explicated: “Sensitivity analysis also included different hierarchical orders, e.g. cardiovascular death replacing overall death, and added additional outcomes, e.g. quality of life.”

There are two main observations: Most patients with DDAF did not experience events throughout the follow-up. After integration of death, thrombotic events, and major bleeds with or without quality of life as an additional outcome, this analysis did not find an advantage of anticoagulation with edoxaban over no anticoagulation in patients with DDAF. Anticoagulation decisions must balance stroke prevention and increased risk of bleeding in patients with DDAF. AFNET board chair Prof. Paulus Kirchhof, UKE, principal investigator of NOAH – AFNET 6, concluded: “The present analysis suggests that a treatment strategy consisting of no anticoagulation and an ECG every six months is acceptable in most patients with DDAF. Individual treatment decisions should include patient preferences. Further analyses may help to better define subpopulations of patients with DDAF in whom anticoagulation therapy is sufficiently effective to justify the increase in bleeding.”

References

(1) Becher N, Koellner G, Blomstrom-Lundqvist C, Camm AJ, Dan GA, Dichtl W, Goette A, De Groot JR, Mont L, Rohrer U, Schotten U, Toennis T, Vardas P, Zapf A, Kirchhof P. Effects of anticoagulation or placebo in patients with device-detected atrial fibrillation and multiple stroke risk factors: A win ratio and win odds analysis of the NOAH-AFNET 6 trial. Abstract ESC Congress 2025

(2) Becher N, Koellner G, Blomstrom-Lundqvist C, Camm AJ, Dan GA, Dichtl W, Goette A, De Groot JR, Mont L, Rohrer U, Schotten U, Toennis T, Vardas P, Zapf A, Kirchhof P. Effects of anticoagulation in patients with device-detected atrial fibrillation and multiple stroke risk factors: A Win Ratio analysis of the NOAH-AFNET 6 trial l. Eur Heart J Qual Care Clin Outcomes. 2025 Sep 01.  DOI:10.1093/ehjqcco/qcaf087

(3) Kirchhof P, Toennis T, Goette A, et al. Anticoagulation with Edoxaban in Patients with Atrial High-Rate Episodes. N Engl J Med 2023; 389:1167-1179. DOI:10.1056/NEJMoa2303062.

(4) Toennis T, Bertaglia E, Brandes A, et al. The influence of Atrial High Rate Episodes on Stroke and Cardiovascular Death – An update. Europace. 2023 Jul 4;25(7). DOI:10.1093/europace/euad166.

(5) Becher N, Toennis T, Bertaglia E, et al. Anticoagulation with edoxaban in patients with long Atrial High-Rate Episodes ≥24 hours. Eur Heart J. 2024 Mar 7;45(10):837-849. DOI:10.1093/eurheartj/ehad771

(6) Lip YH, Nikorowitsch J, Sehner S et al. Oral anticoagulation in device-detected atrial fibrillation: effects of age, sex, cardiovascular comorbidities, and kidney function on outcomes in the NOAH-AFNET 6 trial. Eur Heart J. 2024 April 9. DOI:10.1093/eurheartj/ehae225

(7) Diener HC, Becher N, Sehner S, Toennis T et al. Anticoagulation in patients with device-detected atrial fibrillation with and without a prior stroke or transient ischemic attack. The NOAH-AFNET 6 trial. J Am Heart Assoc. 2024 Sep 3;13(17):e036429. DOI:10.1161/JAHA.124.036429

(8) McIntyre WF, Benz AP, Becher N, et al. Direct Oral Anticoagulants for Stroke Prevention in Patients with Device-Detected Atrial Fibrillation: A Study-Level Meta-Analysis of the NOAH-AFNET 6 and ARTESiA Trials. Circulation. 2024 Mar 26;149(13):981-988. DOI:10.1161/CIRCULATIONAHA.123.067512

(9) Schnabel RB, Benezet-Mazuecos J, Becher N, McIntyre WF et al. Anticoagulation in patients with device-detected atrial fibrillation with and without concomitant vascular disease – A combined secondary analysis of the NOAH-AFNET 6 and ARTESiA trials. Eur Heart J. 2024 Dec 7;45(46):4902-4916. DOI:10.1093/eurheartj/ehae596

About the Atrial Fibrillation NETwork (AFNET)

The Atrial Fibrillation NETwork is an interdisciplinary research network comprising scientists and physicians from hospitals and practices dedicated to improving the management of atrial fibrillation through coordinated research in Germany, Europe, and worldwide. Its main objective is to conduct high quality investigator-initiated clinical trials and registries on a national and international level as well as translational research projects. The AFNET continues the long-term activities of the network which has been funded by the German Federal Ministry of Research and Education over a decade. Since January 2015, specific projects and infrastructures of the AFNET are funded by the German Centre for Cardiovascular Research (DZHK), and some projects by EU research grants. AFNET has long expertise in the management of atrial fibrillation, but also provides support for work in other fields informing cardiovascular care. The results of 20 years of clinical and translational research improved the lives of patients with cardiovascular diseases and influenced treatment guidelines.

Funding of the NOAH – AFNET 6 trial: AFNET, DZHK, Daiichi Sankyo

NOAH – AFNET 6 registration: NCT 02618577, ISRCTN 17309850

Thurs., 14.11.2024

New treatment option for acute stroke in atrial fibrillation in a clinical trial

Press release

Patients with an acute stroke and atrial fibrillation have a particularly high risk of a recurrent stroke and other serious cardiovascular events. A Europe-wide clinical trial led by scientists from the University Medical Centre Hamburg-Eppendorf (UKE) is now investigating whether early rhythm-control treatment can effectively and safely prevent strokes. The EU is funding the project with seven million euros over the next six years.

In the international EAST-STROKE (‘Early treatment of Atrial fibrillation for Stroke prevention Trial in acute STROKE’) trial, patients with atrial fibrillation and an acute ischaemic stroke receive early rhythm-control therapy in addition to the usual stroke and atrial fibrillation treatment. This involves treatment with antiarrhythmic drugs, cardioversion and, in individual cases, atrial fibrillation ablation. These treatments can normalise the irregular heartbeat of those affected. Preliminary findings suggest that rhythm control can prevent strokes and other cardiovascular events. This treatment, which is already established in atrial fibrillation therapy, has rarely been used in acute stroke patients due to the potential risks and side effects. ‘If the study confirms the results of our preliminary analysis, it could change clinical practice in the treatment of stroke patients with atrial fibrillation worldwide and help prevent many thousands of new strokes,’ says project coordinator Prof Dr Götz Thomalla, Director of the Department of Neurology at the UKE.

No increased complication rate after a previous stroke

The study is primarily based on preliminary work by UKE scientists. In the EAST-AFNET 4 study led by Prof Dr Paulus Kirchhof, Atrial Fibrillation Network (AFNET) and Department of Cardiology at the UKE, the benefits of early rhythm-control therapy in patients with atrial fibrillation were demonstrated four years ago. Three years later, Dr Märit Jensen, Clinic and Polyclinic for Neurology at the UKE, was able to show that this treatment is particularly beneficial and safe in the subgroup of patients with atrial fibrillation and a history of stroke. In the trial now starting, rhythm-control therapy will be initiated shortly after the acute stroke. ‘The study is an excellent example of cooperation between cardiology and neurology in the innovative treatment of patients with stroke,’ says Prof Kirchhof, co-coordinator of the study.

EAST-STROKE is being funded by the EU as part of ‘Horizon Europe’ and is initially being started in 42 clinics in Germany, Spain, Switzerland and the Netherlands; the participation of other countries is planned in the course of the programme. A total of 1746 patients will be included in the study, which is scheduled to start at the beginning of 2025. ‘The plan for EAST-STROKE has already met with a great response. Partner studies are currently being prepared in an international collaboration in Australia, Brazil and the USA, among others,’ says study coordinator Dr Märit Jensen.

About the Atrial Fibrillation NETwork (AFNET)

The Atrial Fibrillation NETwork is an interdisciplinary research network comprising scientists and physicians from hospitals and practices dedicated to improving the management of atrial fibrillation through coordinated research in Germany, Europe, and worldwide. Its main objective is to conduct high quality investigator-initiated clinical trials and registries on a national and international level as well as translational research projects. The AFNET continues the long-term activities of the network which has been funded by the German Federal Ministry of Research and Education over a decade. Since January 2015, specific projects and infrastructures of the AFNET are funded by the German Centre for Cardiovascular Research (DZHK), and some projects by EU research grants. AFNET has long expertise in the management of atrial fibrillation, but also provides support for work in other fields informing cardiovascular care. The results of 20 years of clinical and translational research improved the lives of patients with cardiovascular diseases and influenced treatment guidelines.

www.kompetenznetz-vorhofflimmern.de

Kompetenznetz Vorhofflimmern e.V. (AFNET)

Mendelstraße 11

48149 Münster

Tel.: 0251 9801330

info@kompetenznetz-vorhofflimmern.de

Contact for questions

Dr. Märit Jensen

Department of Neurology

University Medical Center Hamburg-Eppendorf (UKE)

Martinistraße 52

20246 Hamburg, Germany

Telefon: +49 40 7410-53770

m.jensen@uke.de

Contact public relations office

Communications and public relations

University Medical Center Hamburg-Eppendorf (UKE)

Martinistraße 52

20246 Hamburg, Germany

Telefon: +49 40 7410-56061

presse@uke.de

Mo., 14.10.2024

Does early catheter ablation improve outcomes in patients with atrial fibrillation and comorbidities?

Press release

Many patients with atrial fibrillation (AF) experience stroke, cardiovascular death and other cardiovascular complications. Early rhythm control can prevent some of these events but is often withheld from elderly patients with multiple comorbidities. Catheter ablation is the most effective rhythm-controlling therapy but has mainly been tested in younger patients. The German Atrial Fibrillation Network (AFNET) initiated the EASThigh – AFNET 11 trial to investigate whether early catheter ablation can reduce outcomes in patients with AF and comorbidities. EASThigh – AFNET 11 enrolled the first patient on 14.10.2024.

Atrial fibrillation (AF) epidemic affects the health of a growing number of people worldwide. Patients with AF are at risk of stroke, heart failure, death and dementia. Many patients develop AF in old age, and older people with cardiovascular comorbidities are at highest risk of AF-related complications.

The EAST – AFNET 4 trial, successfully completed in 2020, and subsequent sub-analyses demonstrated that systematic rhythm control therapy, initiated early in all patients using antiarrhythmic drugs or AF ablation, can reduce AF-related complications compared to usual care (1). These findings and subsequent analyses by others shifted the AF treatment paradigm towards earlier and broader use of rhythm control therapy.

Prespecified secondary analyses of the EAST – AFNET 4 data suggest that patients with AF and a high comorbidity burden benefit most from early rhythm control (2). The outcome-reducing effect of early rhythm control is mediated by attaining sinus rhythm (3). AF ablation targeting the pulmonary veins is the most effective rhythm control therapy and is therefore an attractive rhythm control therapy in patients with a high comorbidity burden who need multiple other medications and are at high risk of recurrent AF. Therefore, the Early atrial fibrillation Ablation for STroke prevention in patients with high comorbidity burden (EASThigh – AFNET 11) trial evaluates early AF ablation targeting the pulmonary veins as a first-line rhythm control therapy in elderly patients with multiple comorbidities, defined by a CHA2DS2VASc score of 4 or more. All participants will be randomized 1:1 to either early AF ablation using established single-shot devices or usual care consisting of anticoagulation and guideline-compliant treatment of existing concomitant diseases. EASThigh – AFNET 11 plans to randomize approximately 2350 patients in 200 sites in Europe, Canada and Australia. The primary outcome is a composite of cardiovascular death, stroke and hospitalization due to heart failure. Safety outcomes include ablation-related complications and mortality.

Rhythm control therapy, and especially AF ablation, is still not often used in elderly patients with AF and comorbidities. The trial will determine the safety and effectiveness of early AF ablation in this understudied population. While AF ablation is a mature technology, there are few controlled trials evaluating the safety of AF ablation in elderly patients with AF and comorbidities. The EASThigh – AFNET 11 investigators intend to fill this evidence gap.

Prof. Paulus Kirchhof, University Medical Center Eppendorf (UKE), Hamburg, Germany, international chief investigator of EASThigh – AFNET 11 and chair of the AFNET board, clarifies the role of catheter ablation: “The outcome-reducing effect of early rhythm control in the EAST – AFNET 4 trial mainly relied on the safe use of established antiarrhythmic drugs. EASThigh – AFNET 11 evaluates a more effective rhythm control therapy, AF ablation. This is a logical and important next step to define the role of early AF ablation to help our patients with AF.” 

Prof. Andreas Goette, St. Vincenz Hospital Paderborn, Germany, member of the EASThigh – AFNET 11 steering committee and of the AFNET board, expresses the expectations of the study as follows: “The results will inform practice guidelines and routine patient care, helping to define the best treatment for patients with AF and a high comorbidity burden. The results of the EASThigh – AFNET 11 trial have great potential to contribute to healthier ageing in a large population at increased risk of premature death, stroke, and heart failure.”

Dr. Andreas Rillig, University Medical Center Eppendorf (UKE), Hamburg, Germany, and co-chief investigator of the EASThigh – AFNET 11 trial states: “To maximize safety and warrant highly consistent efficacy the steering committee decided that early AF ablation will be delivered using single-shot cryoballoon-based isolation of the pulmonary veins in the trial. EASThigh – AFNET 11 is a team effort, thanks to which we can enroll the first patient in the trial today.”

EASThigh – AFNET 11, like EAST – AFNET 4, is an investigator-initiated trial comparing two approved treatment strategies in patients with AF. Sponsor of the trial is AFNET. Following an endorsement by the Global Cardiovascular Research Funders Forum, the trial is currently funded by the Else Kröner-Fresenius-Stiftung (EKFS), other public funders, and by Medtronic. Steering committee members include Paulus Kirchhof AFNET and Hamburg, Germany, Andreas Rillig, Hamburg, Germany, Jason Andrade, Vancouver, Canada, Andreas Goette, AFNET and Paderborn, Germany, José Merino, Madrid, Spain, Andreas Metzner, Hamburg, Jens Cosedis Nielsen, Aarhus, Denmark, Andre Ng, Leicester, UK, Sam Riahi, Aalborg, Denmark, Prash Sanders, Adelaide, Australia, Ulrich Schotten, AFNET and Maastricht, Netherlands, Kevin Vernooy, Maastricht, Stephan Willems, AFNET and Hamburg, Germany, Antonia Zapf, AFNET and Hamburg, Germany and a patient representative who contributes the perspective of those affected.

References

1. Kirchhof P, Camm AJ, Goette A, Brandes A, Eckardt L, Elvan A, Fetsch T, van Gelder IC, Haase D, Haegeli LM, Hamann F, Heidbüchel H, Hindricks G, Kautzner J, Kuck K-H, Mont L, Ng GA, Rekosz J, Schön N, Schotten U, Suling A, Taggeselle J, Themistoclakis S, Vettorazzi E, Vardas P, Wegscheider K, Willems S, Crijns HJGM, Breithardt G, for the EAST–AFNET 4 trial investigators. Early rhythm control therapy in patients with atrial fibrillation. N Engl J Med 2020; 383:1305-1316. DOI: 10.1056/NEJMoa2019422
2. Rillig A, Borof K, Breithardt G, Camm AJ, Crijns HJGM, Goette A, Kuck KH, Metzner A, Vardas P, Vettorazzi E, Wegscheider K, Zapf A, Kirchhof P. Early rhythm control in patients with atrial fibrillation and high comorbidity burden. Circulation. 2022 Sep 13;146(11):836-847. DOI: 10.1161/CIRCULATIONAHA.122.060274
3. Eckardt L et al. Attaining sinus rhythm mediates improved outcome with early rhythm control therapy of atrial fibrillation: the EAST – AFNET 4 trial. Eur Heart J, 2022 Oct 21;43(40):4127-4144. DOI: 10.1093/eurheartj/ehac471

Registration: NCT06324188

About the EAST – AFNET 4 trial

EAST – AFNET 4 was completed in 2020. It was an investigator-initiated trial (IIT) that compared two different treatment strategies in atrial fibrillation (AF). The EAST – AFNET 4 trial tested whether an early, comprehensive rhythm control therapy can prevent adverse cardiovascular outcomes in patients with AF compared to usual care.

A total of 2789 patients with early AF (diagnosed less than a year ago) and at least two cardiovascular conditions (approximating a CHA₂DS₂-VASc score >=2) were enrolled by 135 sites in 11 countries during 2011 to 2016. Patients were randomized 1:1 to early rhythm control therapy or usual care, stratified by sites. Patients in both groups received guideline-recommended treatment for underlying cardiovascular conditions, anticoagulation, and rate control.

All patients in the early rhythm control group received antiarrhythmic drugs or catheter ablation after randomization (chosen by the local study teams). Rhythm control therapy was escalated with AF ablation and/or antiarrhythmic drugs when recurrent AF was documented clinically or by ECG, including monitoring with patient-operated ECG devices.

Patients in the usual care group were initially managed with rate control. Rhythm control therapy was only used to improve AF-related symptoms despite optimal rate control, following current guidelines.

Several publications reported the effects of early rhythm control therapy in different subpopulations and the interaction of early rhythm control therapy with genetic data and biomolecule concentrations in the EAST – AFNET 4 biomolecule study.

EAST – AFNET 4 sub-analyses

• Rillig A et al. Early rhythm control therapy in patients with heart failure. Circulation 2021;144(11):845-858. DOI: 10.1161/CIRCULATIONAHA.121.056323
• Metzner A et al. Anticoagulation, therapy of concomitant conditions, and early rhythm control therapy: a detailed analysis of treatment patterns in the EAST – AFNET 4 trial. EP Europace 2022; 24:552–564. DOI: 10.1093/europace/euab200
• Willems S et al. Systematic, early rhythm control therapy equally improves outcomes in asymptomatic and symptomatic patients with atrial fibrillation: the EAST-AFNET 4 Trial. Eur Heart J. 2022; 43:1219-1230. DOI: 10.1093/eurheartj/ehab593
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• Jensen M et al. Early rhythm-control therapy for atrial fibrillation in patients with a history of stroke: a subgroup analysis of the EAST- AFNET 4 trial. Lancet Neurol 2023; 22: 45–54. DOI: 10.1016/PIIS1474-4422(22)00436-7 
• Van Gelder IC et al; EAST-AFNET 4 Trial Investigators. Sex Differences in Early Rhythm Control of Atrial Fibrillation in the EAST-AFNET 4 Trial. J Am Coll Cardiol. 2023 Feb 28;81(8):845-847. DOI: 10.1016/j.jacc.2022.12.011
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About the Atrial Fibrillation NETwork (AFNET)

The Atrial Fibrillation NETwork is an interdisciplinary research network comprising scientists and physicians from hospitals and practices dedicated to improving the management of atrial fibrillation through coordinated research in Germany, Europe, and worldwide. Its main objective is to conduct high quality investigator-initiated clinical trials and registries on a national and international level as well as translational research projects. The AFNET continues the long-term activities of the network which has been funded by the German Federal Ministry of Research and Education over a decade. Since January 2015, specific projects and infrastructures of the AFNET are funded by the German Centre for Cardiovascular Research (DZHK), and some projects by EU research grants. AFNET has long expertise in the management of atrial fibrillation, but also provides support for work in other fields informing cardiovascular care. The results of 20 years of clinical and translational research improved the lives of patients with cardiovascular diseases and influenced treatment guidelines.

www.kompetenznetz-vorhofflimmern.de

Kompetenznetz Vorhofflimmern e.V. (AFNET)

Mendelstraße 11

48149 Münster

Tel.: 0251 9801330

info@kompetenznetz-vorhofflimmern.de

Press Contact

Dr. Angelika Leute

Tel: 0202 2623395

a.leute@t-online.de

Mo, 02.09.2024

Device-detected atrial fibrillation: Anticoagulation may have greater benefit in patients with vascular disease

Press release

A combined subgroup analysis of the similar trials NOAH – AFNET 6 (1) and ARTESiA (2) revealed: Patients with device-detected atrial fibrillation and concomitant vascular disease are at higher risk of stroke and cardiovascular events and may derive a greater benefit from oral anticoagulation than those without vascular disease. The finding was presented by AFNET Steering Committee member Prof. Renate Schnabel, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany, at the annual congress of the European Society of Cardiology (ESC) in London on 02.09.2024 and published in the European Heart Journal (3).

Device-detected atrial fibrillation (DDAF) are short and typically rare episodes of atrial fibrillation (AF) detected by pacemakers, defibrillators, or implanted loop recorders. Device-detected atrial fibrillation is found in every fifth patient with a cardiac implanted electronic device (4). Device-detected atrial fibrillation can lead to stroke, but the stroke risk in patients with device-detected atrial fibrillation appears lower than the stroke risk in patients with ECG-documented atrial fibrillation (1%/year).

Two recent trials, NOAH – AFNET 6 and ARTESiA, assessed the benefit of anticoagulation in patients with DDAF and stroke risk factors, but without ECG-documented AF. In both trials, patients were randomized either to anticoagulation (edoxaban in NOAH – AFNET 6 and apixaban in ARTESiA) or no anticoagulation in order to compare efficacy and safety outcomes in both groups.

NOAH – AFNET 6 (Non vitamin K antagonist Oral anticoagulants in patients with Atrial High-rate episodes), an investigator-initiated trial conducted by the AFNET, was terminated early due to an expected increase in bleeding events in patients with device-detected atrial fibrillation while the stroke preventing effect was smaller than expected (1). The weak effects of anticoagulation are also found in several subgroups including patients with long episodes of device-detected AF (5), patients with a high comorbidity burden (6), and patients with prior stroke (7).

ARTESiA (Apixaban for the Reduction of Thrombo-Embolism in Patients with Device-Detected Sub-Clinical Atrial Fibrillation) confirmed the low rate of stroke in patients with DDAF and demonstrated a small stroke-reducing effect of anticoagulation (2). A meta-analysis of NOAH – AFNET 6 and ARTESiA confirmed an increase in bleeding and detected a small reduction in ischemic strokes with anticoagulation (8).

Prof. Schnabel, leading investigator of the combined NOAH – AFNET 6 / ARTESiA sub-analysis presented now at the ESC congress, explained the background of this research: “About half of patients with device-detected atrial fibrillation have concomitant vascular disease, i.e. prior stroke or transient ischemic attack (TIA), coronary or peripheral vascular disease. The main goal of our pre-specified subgroup analysis was to assess whether vascular disease affects the efficacy and safety of oral anticoagulation therapy in patients with DDAF. The NOAH – AFNET 6 results were validated in a pre-specified secondary analysis of ARTESiA and meta-analysed.”  

About half of the study population of NOAH – AFNET 6 and ARTESiA (56% in NOAH – AFNET 6; 46% in ARTESiA) had concomitant vascular disease with an established indication for acetylsalicylic acid therapy. In these patients, stroke, myocardial infarction, systemic or pulmonary embolism, or cardiovascular death occurred less often with than without anticoagulation (3.9% versus 5.0% per patient-year in NOAH – AFNET 6 and 3.2% versus 4.4% per patient-year in ARTESiA). Without vascular disease, outcomes were equal with and without anticoagulation (2.7% per patient-year in NOAH – AFNET 6 and 2.3% per patient-year in ARTESiA in both groups). Meta-analysis found consistent results across both trials.

Anticoagulation increased major bleeding in a comparable fashion in patients with vascular disease (edoxaban 2.1% per patient-year; no anticoagulation 1.3% per patient-year; apixaban 1.7% per patient-year; no anticoagulation 1.1% per patient-year) and without vascular disease (edoxaban 2.2% per patient-year; no anticoagulation 0.6% per patient-year; apixaban 1.4% per patient-year; no anticoagulation 1.1% per patient-year).

AFNET board chair Prof. Paulus Kirchhof, UKE, principal investigator of the NOAH – AFNET 6 trial, concluded: “This combined NOAH – AFNET 6 and ARTESiA sub-analysis suggests different effects of anticoagulation in DDAF patients with and without concomitant vascular disease. In the high-risk subgroup of patient with DDAF and vascular disease, anticoagulation therapy appears to reduce thromboembolic events with a greater magnitude than in patients without vascular disease. These data can guide shared clinical decision making on anticoagulation therapy in patients with DDAF.”

References

(1) Kirchhof P, Toennis T, Goette A, et al. Anticoagulation with Edoxaban in Patients with Atrial High-Rate Episodes. N Engl J Med 2023; 389:1167-1179. DOI: 10.1056/NEJMoa2303062.

(2) Healey JS, Lopes RD, Granger CB et al. Apixaban for Stroke Prevention in Subclinical Atrial Fibrillation. N Engl J Med 2024; 390:107-117. DOI: 10.1056/NEJMoa2310234.

(3) Schnabel R et al. Anticoagulation in patients with device-detected atrial fibrillation with and without concomitant vascular disease – A combined secondary analysis of the NOAH-AFNET 6 and ARTESiA trials. Eur Heart J, accepted. DOI: 10.1093/eurheartj/ehae596

(4) Toennis T, Bertaglia E, Brandes A, et al. The influence of Atrial High Rate Episodes on Stroke and Cardiovascular Death – An update. Europace. 2023 Jul 4;25(7). DOI: 10.1093/europace/euad166.

(5) Becher N, Toennis T, Bertaglia E, et al. Anticoagulation with edoxaban in patients with long Atrial High-Rate Episodes ≥24 hours. Eur Heart J. 2024 Mar 7;45(10):837-849. DOI: 10.1093/eurheartj/ehad771

(6) Lip YH, Nikorowitsch J, Sehner S et al. Oral anticoagulation in device-detected atrial fibrillation: effects of age, sex, cardiovascular comorbidities, and kidney function on outcomes in the NOAH-AFNET 6 trial. Eur Heart J. 2024 April 9. DOI: 10.1093/eurheartj/ehae225

(7) Diener HC, Becher N, Sehner S, Toennis T et al. Anticoagulation in patients with device-detected atrial fibrillation with and without a prior stroke or transient ischemic attack. The NOAH-AFNET 6 trial. JAHA, in press.

(8) McIntyre WF, Benz AP, Becher N, et al. Direct Oral Anticoagulants for Stroke Prevention in Patients with Device-Detected Atrial Fibrillation: A Study-Level Meta-Analysis of the NOAH-AFNET 6 and ARTESiA Trials. Circulation. 2023. DOI: 10.1161/CIRCULATIONAHA.123.067512

Funding of the NOAH trial: AFNET, DZHK, Daiichi Sankyo

NOAH registration: NCT 02618577, ISRCTN 17309850

About the Atrial Fibrillation NETwork (AFNET)

The Atrial Fibrillation NETwork is an interdisciplinary research network comprising scientists and physicians from hospitals and practices dedicated to improving the management of atrial fibrillation through coordinated research in Germany, Europe, and worldwide. Its main objective is to conduct high quality investigator-initiated clinical trials and registries on a national and international level as well as translational research projects. The AFNET continues the long-term activities of the network which has been funded by the German Federal Ministry of Research and Education over a decade. Since January 2015, specific projects and infrastructures of the AFNET are funded by the German Centre for Cardiovascular Research (DZHK), and some projects by EU research grants. AFNET has long expertise in the management of atrial fibrillation, but also provides support for work in other fields informing cardiovascular care. The results of 20 years of clinical and translational research improved the lives of patients with cardiovascular diseases and influenced treatment guidelines.

www.kompetenznetz-vorhofflimmern.de

Kompetenznetz Vorhofflimmern e.V. (AFNET)

Mendelstraße 11

48149 Münster

Tel.: 0251 9801330

info@kompetenznetz-vorhofflimmern.de

Press Contact

Dr. Angelika Leute

Tel: 0202 2623395

a.leute@t-online.de