EAST – AFNET 4 trial: Patients with first diagnosed atrial fibrillation (AF) benefit from early rhythm control
Early rhythm control is useful in patients with atrial fibrillation regardless of the AF pattern. Patients with first diagnosed atrial fibrillation benefit from early rhythm control therapy comparably to patients with paroxysmal or persistent AF. This is the result of a subgroup analysis of the EAST – AFNET 4 trial that was presented by Professor Andreas Goette, St. Vincenz Hospital Paderborn, at the American Heart Association (AHA) congress on 14.11.2021 in Boston .
Cardiovascular events are more common in the first year after diagnosing atrial fibrillation. 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 not considered as a first line therapy so far. In the EAST – AFNET 4 trial a clinical benefit of systematic, early rhythm control therapy was observed in the overall study population. Whether the AF pattern modifies the effects of early rhythm control therapy on cardiovascular outcomes is not known.
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 EAST – AFNET 4 sub-study, Professor Goette and colleagues analyzed the effect of early rhythm control therapy in three groups of patients with different AF patterns: 1048 patients with first diagnosed AF namely enrolled within seven days after their first AF episode, 2042 patients with paroxysmal AF, and 743 patients with persistent AF. They assessed the effect of early rhythm control therapy in each group and compared interactions between AF pattern and key outcomes such as cardiovascular death, stroke, heart failure, acute coronary syndromes, night spent in hospital, serious adverse events of special interest, and all-cause death. Changes in health-related quality of life were compared as well.
Patients with first diagnosed AF (FDAF) were more often enrolled as in-patients (FDAF 24%, persistent AF 14%, paroxysmal AF 11%). The CHA2DS2VASc score (a measure of the stroke risk) was comparable between AF pattern groups. There were no major differences in anticoagulation and treatment of concomitant cardiovascular conditions. Early rhythm control reduced cardiovascular complications in all three AF patterns. Nights spent in hospital and hospitalization due to acute coronary syndrome were increased in FDAF patients randomized to early rhythm control compared to FDAF patients randomized to usual care, while there was no difference between randomized groups in patients with paroxysmal AF or persistent AF.
Professor Goette summarized the results: “The clinical benefit of early rhythm control was consistent in AF patterns in the EAST – AFNET 4 trial. We found a difference in hospitalization rates. Patients with first diagnosed AF spent more nights in hospital and experienced more often hospitalization for acute coronary syndrome when they were randomized to early rhythm control compared to usual care.” He concluded: “In our opinion, the clinical AF pattern should not influence the decision for rhythm control therapy in patients with recently diagnosed atrial fibrillation and concomitant cardiovascular conditions.”
 Goette A, Borof K, Breithardt G, Camm AJ, Crijns HJGM, Kuck KH, Wegscheider K, Kirchhof P for the EAST – AFNET 4 investigators. Patients with first diagnosed atrial fibrillation are at high risk of cardiovascular events and suitable for early rhythm control: The EAST – AFNET 4 trial. Abstract AHA congress 2021
 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).
 Goette A et al for the EAST – AFNET 4 investigators. Patients with first diagnosed atrial fibrillation are at high risk of cardiovascular events and suitable for early rhythm control: The EAST – AFNET 4 trial. Abstract AHA congress 2021
 Kirchhof P et al for the EAST – AFNET 4 trial investigators. Early rhythm control therapy in patients with atrial fibrillation. N Engl J Med 2020; 383:1305-1316.