News

Press release

Patients with atrial fibrillation (AF) benefit from early rhythm control therapy. It reduces cardiovascular deaths, strokes, and other adverse outcomes by 20% compared to usual care. The beneficial effects of early rhythm control were shown by the pan-European EAST – AFNET 4 trial and confirmed by other large health studies. However, what is the price of the new treatment strategy? A cost-effectiveness analysis revealed: the health benefits of early rhythm control come at reasonable additional costs. The analysis was published today in EP Europace, a journal of the European Society of Cardiology (ESC) [1].

Atrial fibrillation is a rising epidemic. The number of AF patients in the European Union is projected to increase to approximately 18 million by 2060. Affected persons are at higher risk for stroke and other adverse events associated with high costs for treatment and long-term care. This leads to an increasing economic burden.

The EAST – AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention) trial investigated whether rhythm control therapy – with antiarrhythmic drugs or atrial fibrillation ablation – delivered within one year after AF diagnosis improves outcomes. The main study result, published in 2020 [2], demonstrated that early rhythm control therapy improves outcomes in patients with AF and comorbidities: early rhythm control with antiarrhythmic drugs and/or AF ablation reduced the primary outcome, a composite of cardiovascular death, stroke, and hospitalisation for worsening heart failure or acute coronary syndrome, in 2,789 patients with early AF and cardiovascular risk factors compared to usual care over a 5-year follow-up.

“The health benefit of early rhythm control is evident. However, the cost-effectiveness of the new treatment strategy has not been evaluated so far. One concern after the publication of the EAST – AFNET 4 main study was whether the additional treatment would add an acceptable or undue financial burden to healthcare systems. In the current analysis, we examined for the first time the cost-effectiveness of early rhythm control compared to usual care,” explained Sophie Gottschalk, Department of Health Economics and Health Services Research, University Medical Center Hamburg-Eppendorf, Hamburg Center for Health Economics, Hamburg, Germany. 

The cost-effectiveness analysis was based on data from the German subsample of the EAST – AFNET 4 trial comprising 1,664 patients (see graphical abstract). Early rhythm control in 832 patients was compared to usual care in 832 patients over a 6-year time horizon and from a German healthcare payer perspective. Cost categories considered in the analysis were hospitalisation and medication costs. The time to the occurrence of a primary outcome and the time survived in the observation period were used as effect measures.

Incremental cost-effectiveness ratios (ICERs) were calculated for each effect measure. The ICER value describes the additional costs needed for an additional year free of primary outcome events or an additional life year, respectively. The analysis showed: early rhythm control was associated with higher costs to the amount of €1,924, resulting in ICERs of €10,638 per additional year without a primary outcome, and €22,536 per life year gained. As shown in the uncertainty analysis, high probabilities of cost-effectiveness could be reached if the healthcare payer was willing to pay ≥€55,000 for an additional year without a primary outcome or for a life year gained (probabilities ≥95% or ≥80%, respectively).

The principal investigator of EAST – AFNET 4, Prof. Paulus Kirchhof, Department of Cardiology, Universit Heart and Vascular Center Hamburg-Eppendorf, Hamburg, Germany, concluded: "The health benefits of early rhythm control come at reasonable additional costs as indicated by our analysis of the EAST – AFNET 4 study data for Germany. The added cost is comparable to the cost of other therapies reducing outcomes, and within typical ranges of acceptable payments in Germany. Future studies examining the cost-effectiveness of early rhythm control in other countries, in subgroups with higher benefit from rhythm control therapy, or the cost-effectiveness of different modes of early rhythm control are warranted.”

Notes: ERC, early rhythm control therapy; ICER, incremental cost-effectiveness ratio; primary outcome event = cardiovascular death, stroke, or hospitalisation for stroke or acute coronary syndrome.

References

[1] 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. DOI: 10.1093/europace/euad051

[2] 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

[3] 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

[4] 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

[5] 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

[6] 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

[7] 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. 15 Aug 2022. DOI: 10.1161/CIRCULATIONAHA.122.060274

[8] 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 

[9] 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. DOI: 10.1093/eurheartj/ehac471

Twitter: @afnet_ev, hashtag #EASTtrial.

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

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 2,789 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 randomised 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 randomisation (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. 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).

www.af-net.eu

Press contact

Angelika Leute, PhD

Phone: +49 202 2623395

a.leute@t-online.de

Press release

Patients with atrial fibrillation (AF) and a history of stroke are at high risk of recurrent stroke and cardiovascular complications. Early rhythm control therapy is safe and appears particularly effective in this vulnerable patient group. This was shown by a subgroup analysis of the EAST – AFNET 4 trial. The results were published in The Lancet Neurology [1].

The EAST – AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention) trial investigated whether rhythm control therapy – using antiarrhythmic drugs or atrial fibrillation ablation – delivered within one year after AF diagnosis improves outcomes. The main study result, published in 2020 [2], demonstrated that early rhythm control therapy reduced cardiovascular events by 21% in patients with AF and comorbidities: Early rhythm control (ERC) with antiarrhythmic drugs and/or AF ablation reduced the primary outcome, a composite of cardiovascular death, stroke, and hospitalization for worsening heart failure or acute coronary syndrome, in 2789 patients with early AF and cardiovascular risk factors compared to usual care (UC) over a 5-year follow-up time.

Dr. Märit Jensen from University Medical Center Hamburg Eppendorf (UKE), Hamburg, Germany, who presented the results at the World Stroke Congress, explained the background of this subgroup analysis of the EAST – AFNET 4 trial: “Ten to fifteen percent of patients with AF have a history of stroke. They are at very high risk of recurrent stroke and cardiovascular events. Because of their age, comorbidities, and often due to long-term disabilities after a stroke, these patients rarely receive rhythm control therapy at present. A strategy of systematic, early rhythm control leads to a significant reduction of stroke and cardiovascular events in patients with recently diagnosed AF. However, patients with AF and prior stroke are often frail and multimorbid and may be at particular risk of side effects of rhythm control therapy. Thus, we analysed whether early rhythm control therapy is safe and can prevent adverse cardiovascular outcome in these patients.”

217 participants (8%) of the EAST – AFNET 4 trial had a history of stroke. Their median age was 72 years. 44% of them were women and mean CHA2DS2-VASc score was 5. Of those 217 patients, 110 (51%) were assigned to early rhythm control and 107 (49%) to usual care.

A first primary outcome event – a composite of death from cardiovascular causes, stroke, or hospitalization with worsening of heart failure or acute coronary syndrome – occurred in 18 of the patients assigned to early rhythm control (3.7 per 100 person years) and in 33 patients assigned to usual care (7.4 per 100 person years) translating into a hazard ratio of 0.52 (95% confidence interval 0.29 to 0.93).

A primary safety outcome – a composite of death, stroke, or serious adverse events related to rhythm-control therapy – occurred in 17 (16%) patients assigned to early rhythm control and in 30 (28%) patients assigned to usual care. Mortality was lower in patients assigned to early rhythm control (10% vs. 20%).

Dr. Jensen commented on the findings: “Among patients with AF and history of stroke, early rhythm control therapy was associated with a lower risk of adverse cardiovascular outcomes than usual care. The rate of serious adverse events related to antiarrhythmic drugs or AF ablation in the early rhythm control group (3%) did not exceed the rate observed in patients without history of stroke (5%).”

Götz Thomalla, Professor for Clinical Stroke and Imaging research at the UKE and co-author of the study commented: “In this subgroup analysis, the effects of early rhythm control in patients with a history of stroke were consistent with the findings of the primary analysis. Early rhythm control therapy is effective in preventing adverse cardiovascular outcomes in patients with AF who had a stroke. This highlights the importance of good collaboration between neurologists and cardiologists in secondary prevention of stroke patients with atrial fibrillation.”

The principal investigator of EAST – AFNET 4, Professor Paulus Kirchhof, UKE, concluded: “The results of this subgroup analysis point towards a particular effectiveness of early rhythm control treatment in patients with AF and a history of stroke, a subgroup of patients with a well-known high risk of recurrent stroke or other cardiovascular morbidity and mortality. Importantly, early rhythm control appeared equally safe as in patients without prior stroke. Our findings support the use of early rhythm control in patients with AF and history of stroke in addition to anticoagulation and therapy of concomitant cardiovascular conditions.”

Since the publication of the main study result in 2020, different subgroup analyses of the EAST – AFNET 4 study data have been performed. One described the different, variable treatment patterns of antiarrhythmic drugs and AF ablation used in the trial, applied within guideline recommendations [3]. Other subgroup analyses demonstrated the prognostic benefit of early rhythm control in patients with AF and heart failure [4], in patients with asymptomatic AF [5], in patients with different AF patterns [6], and in patients with high comorbidity burden [7]. A mediator analysis identified sinus rhythm as key factor for the effectiveness of early rhythm control [8].

References

[1] 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

[2] 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

[3] 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

[4] 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

[5] 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

[6] 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

[7] 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. 15 Aug 2022. DOI: 10.1161/CIRCULATIONAHA.122.060274

[8] 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. DOI: 10.1093/eurheartj/ehac471

Follow us on Twitter @afnet_ev and hashtag #EASTtrial.

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

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. 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). www.af-net.eu

Press Contact

Angelika Leute, PhD

Phone: +49 202 2623395

a.leute@t-online.de

Press release

Consumer electronics provide a novel route to screen for atrial arrhythmias. The Smart in OAC – AFNET 9 study offered smartphone and wearable-based continuous arrhythmia screening to older adults and detected atrial arrhythmia in five percent of the participants. The results of the study performed by AFNET were published in the European Heart Journal of Digital Health [1].

Atrial fibrillation (AF) is the most common arrhythmia and a rising epidemic. It affects several million people in Europe. In many people the arrhythmia is asymptomatic and often remains unnoticed for a long time. However, risk of stroke and other complications may be elevated in older adults with atrial arrhythmias. Detection of atrial arrhythmias by screening potentially enables earlier therapy, to prevent complications, for example by starting anticoagulation in order to prevent strokes.

The Smart in OAC – AFNET 9 (Smartphone and wearable detected atrial arrhythmia in Older Adults Case finding) study offered continuous atrial arrhythmia screening to unselected people aged over 65 years without known atrial fibrillation and not receiving oral anticoagulation. The principal investigator of Smart in OAC – AFNET 9, Professor Larissa Fabritz, University Medical Center Hamburg Eppendorf (UKE), Hamburg, Germany and University of Birmingham, UK, explained the background of the study: “Simple, scalable methods to identify atrial arrhythmias in at-risk populations are needed to enable timely detection of AF and initiation of therapy. To address this societal need, we performed the Smart in OAC – AFNET 9 study and evaluated the usability of a fully digital detection system for atrial arrhythmias in unselected older European adults.” The study design was published in [2].

Smart in OAC – AFNET 9 was performed in Germany, Poland and Spain during the Covid-19 pandemic. Between 01.02.2021 and 31.01.2022, 882 senior citizens aged between 65 and 90 years recorded signals. Their mean age was 71±5 years. Of these, 500 (57%) were women, 414 (47%) had high blood pressure, 97 (11%) diabetes.

Senior citizens were invited to participate by various ways. The majority of participants (72%) were reached by media campaigns in newspapers and television or by word of mouth and town hall meetings for senior citizens. The remaining participants were attracted by leaflets (11%), identified by general practitioners made aware of the study (9%), a website (4%), outpatient clinics (2%) or pharmacies (2%).

Participants received a wristband with a photo plethysmography (PPG) sensor to detect the pulse coupled to an app on their smartphone, enabling fully remote continuous rhythm monitoring for up to eight weeks. Over half of the participants (53%) participated without any in-person contact, while 47% of participants received personal assistance with the device.

During the first four weeks, participants transmitted PPG signals for 533 hours, 77% of the maximal observation time of 696 hours. Atrial arrhythmia was detected in 44 participants (5%) within 28 days, and in 53 (6%) within eight weeks. Atrial arrhythmia detection was higher in the first week of monitoring (incidence rate 3.4% in week 1) compared to the subsequent weeks (incidence rate 0.55% in weeks 2-4).

rofessor Fabritz concluded: “Smart in OAC – AFNET 9 successfully used a smartphone and wearablebased system to detect atrial arrhythmias in older people in several European countries. Offers of remote technical assistance were accepted and compliance was high, showing feasibility for this age group. Our screening identified atrial arrhythmias in 5% of older adults. Detection rates were high in the first week of monitoring, and tapered off thereafter, suggesting that relatively short monitoring periods may be sufficient to detect older adults with atrial arrhythmias. These findings encourage the use of fully digital, consumer-electronics based systems to screen for atrial arrhythmias in unselected older adults.”

Smart in OAC – AFNET 9 is an investigator-initiated study. It was initiated and conducted by AFNET. Financial support was provided by Daiichi-Sankyo, in-kind support by Preventicus.

References

[1] Fabritz L, Connolly DL, Czarnecki E, Dudek D, Guasch E, Haase D, Huebner T, Zlahoda-Huzior A, Jolly K, Kirchhof P, Obergassel J, Schotten U, Vettorazzi E, Winkelmann S, Zapf A, Schnabel RB, for the Smart in OAC - AFNET 9 investigators. Wearable-based detection of atrial arrhythmias in older adults. The fully digital European Smart in OAC – AFNET 9 case finding study. Eur Heart J Digital Health. 22.11.2022. doi: 10.1093/ehjdh/ztac067

[2] Fabritz L, Connolly D, Czarnecki E, Dudek D, Zlahoda-Huzior A, Guasch E, Haase D, Huebner T, Jolly K, Kirchhof P, Schotten U, Zapf A, Schnabel R. Remote Design of a Smartphone and Wearable Detected Arial Arrhythmia in Older Adults Case Finding Study: Smart in OAC - AFNET 9. Front Cardiovasc Med. 21.03.2022. doi:10.3389

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. 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). www.af-net.eu

Pressekontakt

Angelika Leute, PhD

Phone: +49 202 2623395

a.leute@t-online.de

Press release

In the AXADIA – AFNET 8 trial, oral anticoagulation with the non-vitamin K antagonist oral anticoagulant (NOAC) Apixaban appeared equally safe and effective as vitamin K antagonists (VKA) in patients with atrial fibrillation (AF) and severe chronic kidney disease. The results were presented at the American Heart Association (AHA) congress on 06.11.2022 in Chicago, USA [1] and simultaneously published in Circulation [2].

AXADIA – AFNET 8 (A Safety Study Assessing Oral Anticoagulation with ApiXAban versus Vitamin KAntagonists in Patients with Atrial Fibrillation and End-Stage Kidney Disease on Chronic HemoDIAlysis Treatment) is an investigator-initiated trial with the objective of improving oral anticoagulation in patients with atrial fibrillation and chronic kidney disease on hemodialysis. It compared the NOAC Apixaban to VKA in these multimorbid patients.

Professor Holger Reinecke, University Hospital Münster, Germany, principal investigator of AXADIA – AFNET 8, explained the background of the trial: “Patients with atrial fibrillation and chronic kidney disease are at high risk for stroke and therefore in dire need of antithrombotic therapy. However, anticoagulation is challenging in this vulnerable patient group. These patients are prone to bleeding and show a high rate of life-threatening complications under oral anticoagulation as we know from the experience with VKA.”

In the past few years, NOACs have become the standard therapy for preventing stroke and ischemic thromboembolism in patients with AF, but the efficacy and safety of NOACs in patients on hemodialysis is not well known. The NOAC Apixaban was chosen for this trial because it is mainly eliminated via metabolization and excretion in the liver, rendering Apixaban a suitable NOAC in patients with chronic kidney disease.

From June 2017 until May 2022, 39 study sites in Germany randomized 97 patients with AF on chronic hemodialysis to either Apixaban (2.5 mg bid) (48 patients) or the VKA phenprocoumon (INR 2.0-3.0) (49 patients). The median follow-up time was 429 (range 37-1,370) versus 506 (range 101- 1,379) days, respectively.

The composite primary safety endpoint – defined by a first event of major bleeding, clinicallyrelevant non-major bleeding, or all-cause death – occurred in 22 (45.8%) patients on Apixaban and in 25 (51.0%) patients on VKA (HR 0.931, 95% CI 0.525-1.651, p(noninferiority)=0.1567).

The primary efficacy endpoint – a composite of ischemic stroke, all-cause death, myocardial infarction, and deep vein thrombosis and/or pulmonary embolism – occurred in 10 (20.8%) patients on Apixaban and in 15 (30.6%) patients on VKA (p=0.51, log rank).

There were no significant differences regarding individual outcomes (mortality 18.8% vs. 24.5%; major bleedings 10.4 vs. 12.2%; myocardial infarctions 4.2. vs. 6.1%, respectively).

Professor Reinecke concluded: “AXADIA – AFNET 8 was not able to recruit the planned number of participants in this multimorbid patient population. Thus, we missed the predefined non-inferiority margin for apixaban to VKA. Nevertheless, in this largest prospective trial in patients with AF on hemodialysis with long follow-up, Apixaban appears equally safe and effective as VKA. The results also show: even on oral anticoagulation, patients with AF on hemodialysis remain at high risk of cardiovascular events. Taken together with other observational publications, our findings support the use of Apixaban in patients with AF on hemodialysis.”

AXADIA – AFNET 8 was initiated and conducted by AFNET. Financial Support was provided by BristolMyers Squibb and Pfizer.

References

Reinecke H, Bauersachs R, Breithardt G, Engelbertz C, Gerss J, Goerlich D, Juergensmeyer S, Wanner C, Kirchhof P. 2022. Apixaban or Vitamin K Antagonists for Stroke Prevention in Patients with Atrial Fibrillation on Hemodialysis: Results of the Randomized AXADIA – AFNET 8 trial. AHA congress abstract 2022

Reinecke H, Engelbertz C, Bauersachs R, Breithardt G, Echterhoff H, Gerss J, Haeusler KG, Hewing B, Hoyer J, Juergensmeyer S, Klingenheben T, Knapp G, Rump LC, Schmidt-Guertler H, Wanner C, Kirchhof P, Goerlich D. 2022. A randomized controlled trial comparing apixaban to the vitamin K antagonist phenprocoumon in patients on chronic hemodialysis – the AXADIA – AFNET 8 study. Circulation 06.11.2022. doi: 10.1161/CIRCULATIONAHA.122.062779

Reinecke H, Jürgensmeyer S, Engelbertz C, Gerss J, Kirchhof P, Breithardt G, Bauersachs R, Wanner C. Design and rationale of a randomised controlled trial comparing apixaban to phenprocoumon in patients with atrial fibrillation on chronic haemodialysis: the AXADIA – AFNET 8 study. BMJ Open 2018 Sep 10. doi: 10.1136/bmjopen-2018-02269

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. 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). www.af-net.eu

Pressekontakt

Angelika Leute, PhD

Phone: +49 202 2623395

a.leute@t-online.de

The results of the AXADIA-AFNET8 trial and another EAST-AFNET4 subanalysis will be presented at this year's AHA congress (Chicago, US) :

Featured Science Session (FS.03): Featured Science in Heart Rhythm Medicine
Apixaban or vitamin K antagonists for stroke prevention in patients with atrial fibrillation on hemodialysis: Results of the randomized AXADIA-AFNET 8 trial
Monday, 7th of November 2022 | 0:20 – 0:30 (CET) / Sunday, 6th of November 2022 | 5:20pm – 5:30pm (CST)
Speaker: Dr. Paulus Kirchhof
More information

Featured Science Session (FS.03): Featured Science in Heart Rhythm Medicine
Association of genetic risk and outcomes in patients with early rhythm control therapy in atrial fibrillation: Results from the EAST-AFNET4 trial
Monday, 7th of November 2022 | 0:30 – 0:40 (CET) / Sunday, 6th of November 2022 | 5:30pm – 5:40pm (CST)
Speaker: Dr. Shinwan Kany
More information