AF

1. Early rhythm control therapy in patients with
atrial fibrillation:
Primary results of the EAST – AFNET 4 trial
Paulus Kirchhof, A John Camm, Andreas Goette, Axel Brandes, Lars Eckardt, Arif Elvan, Thomas Fetsch, Isabelle van Gelder,
Doreen Haase, Laurent Haegeli, Frank Hamann, Hein Heidbuchel, Gerhard Hindricks, Josef Kautzner, Karl-Heinz Kuck, Luis Mont,
Andre Ng, Jerzy Rekosz, Norbert Schön, Ulrich Schotten, Anna Suling, Jens Taggeselle, Sakis Themistoclakis,
Eik Vettorazzi, Panos Vardas, Karl Wegscheider, Stephan Willems, Harry JGM Crijns, Günter Breithardt
p.kirchhof@bham.ac.uk / p.kirchhof@uke.de

2. Does early rhythm control therapy improve outcomes compared to usual care in
patients with early, recently diagnosed atrial fibrillation at risk of stroke?
EAST- AFNET 4 is a multi-centre, investigator-initiated trial. Sponsor is AFNET,
supported by AFNET, BMBF, DHS, DZHK, EHRA, Sanofi, St Jude Medical/Abbott.
EAST – AFNET 4 Hypothesis and setting

3. Inclusion Criteria
• Recent onset AF, i.e. AF with a known
history of ≤ 1 year prior to randomization
and
• Risk for stroke as evidenced by
either
a) one of the following: age > 75 years,
prior stroke or transient ischemic attack
(TIA)
or
b) two of the following: hypertension,
diabetes mellitus, left ventricular
hypertrophy, age > 65 years, female sex,
peripheral artery disease, kidney disease
(MDRD stage III or IV), stable heart failure
(NYHA II or LVEF <50%), severe coronary
artery disease (previous myocardial
infarction, CABG or PCI)

4. Design
• Participants will be randomized into one of two groups
receiving either early rhythm control therapy or usual care.
• In the early therapy group, patients will receive either catheter
ablation (usually by pulmonary vein isolation) or adequate
antiarrhythmic drug therapy directly after randomization. The
initial therapy will be selected by the investigator. Upon AF
recurrence, both modalities will be combined.
• Usual care will be conducted following the current ESC
guidelines for AF treatment. In addition to antithrombotic
therapy and therapy of underlying heart disease, usual care
usually consists of an initial attempt to control symptoms by
rate control therapy.
• Primary outcome parameter: composite of cardiovascular
death, stroke and hospitalization due to heart failure or acute
coronary syndrome.
• All patients are followed up by 6-monthly central follow-up
contacts via questionnaires and by outpatient follow-up visits
at 12, 24 and 36 months.

5. Demographics

6. EAST – AFNET 4 CONSORT diagram
Included in primary analysis n=1,395
2789 patients randomized by 135 sites in 11 countries
Total FU-years lost: 409/6859 (6.0%)
299 FU-years because 79 patients withdrew (4.4%)
110 FU-years lost to FU in 65 patients (1.6%)
Included in primary analysis n=1,394
Total FU-years lost: 582/6963 (8.4%)
465 FU-years because 115 patients withdrew (6.7%)
117 FU-years lost to follow-up in 56 patients (1.7%)
Early Rhythm Control (n=1,395) Usual Care (n=1,394)
Randomization
Initial Initial 2 year
2 year

7. EAST – AFNET 4 Analysis of first primary outcome
249 patients with event
3.9% per year
316 patients with event
5% per year
Hazard Ratio [96% CI] 0.79 [0.66-0.94], p=0.005

9. EAST – AFNET 4 Conclusions
Early initiation of rhythm control therapy reduced cardiovascular outcomes in patients
with early AF and cardiovascular conditions without affecting nights spent in hospital.
As expected, the early rhythm control strategy was associated with more adverse
events related to rhythm control therapy, but the overall safety of both treatment
strategies was comparable.
These results have the potential to inform the future use of rhythm control therapy,
further improving the care of patients with early AF.
You can read more about the results of the EAST – AFNET 4 trial at
https://www.nejm.org/doi/full/10.1056/NEJMoa2019422