Early rhythm control improves outcomes in patients with asymptomatic atrial fibrillation
Asymptomatic patients with atrial fibrillation (AF) benefit from early rhythm control therapy comparably to symptomatic patients. This is the result of a subgroup analysis of the EAST – AFNET 4 trial that was presented by Professor Stephan Willems, Asklepios Hospital St. Georg, Hamburg, at the annual congress of the European Society of Cardiology (ESC) on 27.08.2021  and published in the European Heart Journal .
Approximately one third of AF patients are asymptomatic. AF is associated with stroke, cardiovascular death, and other cardiovascular complications in patients with or without symptoms. The current guidelines for the management of AF recommend anticoagulation and therapy of concomitant cardiovascular conditions in all patients with AF, while rhythm control is restricted to symptomatic patients. In the EAST – AFNET 4 trial a clinical benefit of systematic, early rhythm control therapy was observed in the overall study population. Professor Willems and colleagues now investigated whether the beneficial effects of early rhythm control are also present in the subgroup of asymptomatic AF patients.
The EAST – AFNET 4 trial investigated whether rhythm control therapy – with antiarrhythmic drugs or ablation – delivered within one year after AF diagnosis improves outcomes. The main study result, published last year , demonstrated a clinical benefit of early rhythm control therapy for all patients: Early rhythm control therapy with antiarrhythmic drugs and/or AF ablation reduced 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 over a 5-year follow-up time.
In the present subgroup analysis, the effect of early rhythm control was analyzed in all asymptomatic patients enrolled in the EAST – AFNET 4 trial and compared to symptomatic patients.
At baseline, 801/2633 (30.4%) patients were asymptomatic, whereas 1832/2633 (69.6%) patients were symptomatic. Baseline characteristics of asymptomatic compared to symptomatic patients were comparable, with slight differences in the type of comorbidities. The rate of heart failure was lower in asymptomatic patients (169/801 (21.1%)) compared to symptomatic patients (569/1832 (31.1%)) and fewer women were asymptomatic (300/801 (37.5%)) than symptomatic (923/1832 (50.4%)).
Anticoagulation and treatment of concomitant cardiovascular conditions was not different between asymptomatic and symptomatic patients. Following the trial protocol, asymptomatic patients randomized to early rhythm control received an almost identical early rhythm control therapy compared to symptomatic patients.
The primary outcome (a composite of cardiovascular death, stroke, or hospitalization for worsening heart failure or acute coronary syndrome) occurred in 79/395 asymptomatic patients randomized to early rhythm control, and in 97/406 asymptomatic patients randomized to usual care, almost identical to the overall study population. The beneficial effect of rhythm control therapy on cardiovascular complications in asymptomatic patients with AF is not different from the effect in symptomatic patients.
Professor Willems summarizes: “The prognostic benefit of early rhythm control observed in the general EAST population is maintained in asymptomatic patients. Our results call for a shared decision process discussing the benefits of rhythm control therapy in all patients with recently diagnosed atrial fibrillation and concomitant cardiovascular conditions regardless of their AF-related symptoms.”
Professor Paulus Kirchhof, UKE Hamburg, principal investigator of the EAST – AFNET 4 trial and the last author of the analysis, observes: “This new analysis emphasizes the safety and effectiveness of early rhythm control therapy in asymptomatic patients with AF. The findings have implications for the optimal care of our asymptomatic patients with atrial fibrillation in clinical practice.”
 Willems S, Borof K, Brandes A, Breithardt G, Camm AJ, Crijns HJGM, Eckardt L, Gessler N, Haegeli LM, Heidbuchel H, Schnabel R, Szumowski L, van Gelder IC, Wegscheider K, Kirchhof P. Benefit of early rhythm control therapy in patients with asymptomatic AF – insights from the EAST – AFNET 4 trial. Abstract ESC congress 2021
 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. 2021 (published ahead of print)
 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.
Angelika Leute, PhD
Phone: +49 202 2623395
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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 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).
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. 2021