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People with atrial fibrillation benefit from early rhythm maintenance (EAST-AFNET 4 trial)

Especially older patients with atrial fibrillation and other diseases should be treated early with a rhythm-preserving therapy. |©Photographee.eu - stock.adobe.com

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Patients with atrial fibrillation benefit from early rhythm-maintenance therapy. It prevents complications better than the usual treatment. This is the result of the EAST-AFNET 4 study conducted by the Atrial Fibrillation NETwork (AFNET). Analyses of various subgroups of the study population have since shown that this result generally applies - to all types of atrial fibrillation regardless of other diseases or special features of those affected. Therefore, cardiologists recommend that all people with newly diagnosed atrial fibrillation be offered rhythm-maintaining treatment by catheter ablation or antiarrhythmic drugs in a timely manner.

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Atrial fibrillation is the most common cardiac arrhythmia in the elderly, with approximately two million people affected in Germany. Atrial fibrillation is associated with an irregular and often rapid heartbeat. Sufferers have an increased risk of stroke because blood clots form during the arrhythmia, particularly in the left atrium, and can travel with the bloodstream to the brain. Patients with this cardiac arrhythmia often die prematurely or suffer severe sequelae, even when treated according to current guidelines.

Today, atrial fibrillation is usually treated with drugs that regulate the heart rate and thus protect the heart muscle from overload. Affected patients are also given anticoagulants (oral anticoagulation) to reduce the risk of stroke. In addition to this previously standard treatment, there are rhythm medications (antiarrhythmics) and non-drug measures (catheter ablation) to restore and maintain normal heart rhythm (sinus rhythm). These rhythm-maintaining measures, which can potentially also entail risks and side effects, have been used primarily for patients suffering from severe symptoms. Whether rhythm-maintaining treatment only alleviates symptoms, prevents complications and hospitalizations, and prolongs the lives of those affected was previously unclear. Scientific evidence for this was lacking.

The EAST-AFNET-4 trial (Early Treatment of Atrial Fibrillation for Stroke Prevention) showed in its main result, published in 2020, that early rhythm-maintaining therapy with drugs or catheter ablation, started within one year after the diagnosis of atrial fibrillation, prevents deaths, strokes and hospitalizations due to heart failure or a so-called acute coronary syndrome, i.e. a potential circulatory disorder of the heart muscle, more effectively than the previously used treatment [1]. Whether this result applies to all people with atrial fibrillation or whether limitations may apply to patients with certain special features was examined in subanalyses. In these, specific subgroups of study participants were examined more closely, particularly those who previously seemed less suitable for rhythm-maintaining therapy.

A new subanalysis shows: People with comorbidities also benefit from early rhythm maintenance

In the latest subanalysis, the role of comorbidities was investigated. The scientific director of the EAST-AFNET-4 study, Professor Paulus Kirchhof from the University Heart and Vascular Center UKE, Hamburg, explains: "We usually tend to offer rhythm-maintenance therapy to relatively young and healthy patients with atrial fibrillation. Now, within the EAST-AFNET-4 study population, we have analyzed in more detail the group of elderly people with atrial fibrillation and several additional diseases, especially those that increase the risk of stroke as well as myocardial infarction, and found out: Even in these people, early rhythm-maintaining therapy prevents complications better than usual care. These very sick patients in particular should therefore be treated with rhythm-maintaining measures as a matter of priority in order to be protected from secondary damage." The results will soon be published in the renowned journal Circulation [2].

Over the past two years, subgroup analyses have also been performed on the following specific questions:

  1. Rhythm maintenance in heart failure: what applies when atrial fibrillation occurs with heart failure or impaired cardiac pump function? For this group, which accounts for about one-third of EAST-AFNET-4 trial participants, the benefit of early rhythm-maintaining treatment was confirmed beyond doubt [3].
  2. Rhythm maintenance in asymptomatic patients: Atrial fibrillation is not always associated with typical symptoms. Many affected individuals do not feel symptoms and only learn by chance that they suffer from a rhythm disturbance. These asymptomatic patients also benefit from early rhythm-maintenance therapy [4].
  3. Rhythm maintenance even in persistent atrial fibrillation: What role does the type of AF play? As the data show, early rhythm maintenance protects all patients with AF from complications, regardless of whether they have recurrent AF attacks or persistent AF, or were first diagnosed with arrhythmia. However, in the latter group, rhythm-maintaining measures more often resulted in hospitalization. Therefore, the benefit for these individuals remains unclear [5].
  4. Rhythm maintenance in men and women: Are there gender differences to consider? Comparing trial data from men and women, early rhythm-maintaining therapy was shown to be beneficial in both sexes. However, regardless of treatment strategy, women suffered fewer complications overall than men [6].

The researchers also investigated whether differences in treatment in the two study groups might have distorted the results. Detailed analyses dispelled these doubts. In both study groups, anticoagulation and the treatment of concomitant diseases were carried out equally in accordance with the currently valid guidelines [7].

Prof. Kirchhof summarizes the conclusion of the EAST-AFNET-4 scientists: "Two years of careful analyses in the complete data set of the EAST-AFNET-4 trial have proven the benefit and safety of early rhythm maintenance for all patients in the EAST-AFNET-4 trial. The results of the EAST-AFNET-4 trial have already led to appropriate adjustments in treating atrial fibrillation in clinical practice in many centers. Rhythm-maintenance measures should now no longer serve only to treat symptoms. Still, they should be offered to all people with atrial fibrillation and an increased risk of atrial fibrillation-associated complications promptly after diagnosis." An international group of experts also formulated corresponding recommendations based on the EAST-AFNET-4 trial results [8].

The DZHK partially funded the EAST-AFNET-4 study from 2015 to 2020.


[1] 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. DOI: 10.1056/NEJMoa2019422
[2] Rillig A et al. Early rhythm control in patients with atrial fibrillation and high comorbidity burden. Circulation. 15 Aug 2022. DOI: 10.1161/CIRCULATIONAHA.122.060274
[3] 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
[4] 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
[5] Goette A et al. 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
[6] Van Gelder IC et al. Sex Differences in Early Rhythm Control Therapy in Patients with Atrial Fibrillation. Late Breaking Science Abstract, EHRA Congress 2022
[7] 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
[8] Schnabel R et al. Early Diagnosis and Better Rhythm Management to improve outcomes in patients with Atrial Fibrillation: The 8th AFNET/EHRA Consensus Conference. Europace. 2022 Jul 27. DOI: 10.1093/europace/euac062.


Source: Press release Kompetenznetz Vorhofflimmern e.V. (AFNET)