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Randomized Controlled Trial
. 2022 Mar 21;43(12):1219-1230.
doi: 10.1093/eurheartj/ehab593.

Systematic, early rhythm control strategy for atrial fibrillation in patients with or without symptoms: the EAST-AFNET 4 trial

Stephan Willems  1   2   3 , Katrin Borof  4 , Axel Brandes  5   6 , Günter Breithardt  3   7 , A John Camm  8 , Harry J G M Crijns  9 , Lars Eckardt  3   7 , Nele Gessler  1   2 , Andreas Goette  6   10   11 , Laurent M Haegeli  12   13 , Hein Heidbuchel  14 , Josef Kautzner  15 , G André Ng  16 , Renate B Schnabel  2   4 , Anna Suling  17 , Lukasz Szumowski  18 , Sakis Themistoclakis  19 , Panos Vardas  20 , Isabelle C van Gelder  21 , Karl Wegscheider  2   3   15 , Paulus Kirchhof  2   3   4   22
Affiliations
Randomized Controlled Trial

Systematic, early rhythm control strategy for atrial fibrillation in patients with or without symptoms: the EAST-AFNET 4 trial

Stephan Willems et al. Eur Heart J. .

Abstract

Aims: Clinical practice guidelines restrict rhythm control therapy to patients with symptomatic atrial fibrillation (AF). The EAST-AFNET 4 trial demonstrated that early, systematic rhythm control improves clinical outcomes compared to symptom-directed rhythm control.

Methods and results: This prespecified EAST-AFNET 4 analysis compared the effect of early rhythm control therapy in asymptomatic patients (EHRA score I) to symptomatic patients. Primary outcome was a composite of death from cardiovascular causes, stroke, or hospitalization with worsening of heart failure or acute coronary syndrome, analyzed in a time-to-event analysis. At baseline, 801/2633 (30.4%) patients were asymptomatic [mean age 71.3 years, 37.5% women, mean CHA2DS2-VASc score 3.4, 169/801 (21.1%) heart failure]. Asymptomatic patients randomized to early rhythm control (395/801) received similar rhythm control therapies compared to symptomatic patients [e.g. AF ablation at 24 months: 75/395 (19.0%) in asymptomatic; 176/910 (19.3%) symptomatic patients, P = 0.672]. Anticoagulation and treatment of concomitant cardiovascular conditions was not different between symptomatic and asymptomatic patients. The primary outcome occurred in 79/395 asymptomatic patients randomized to early rhythm control and in 97/406 patients randomized to usual care (hazard ratio 0.76, 95% confidence interval [0.6; 1.03]), almost identical to symptomatic patients. At 24 months follow-up, change in symptom status was not different between randomized groups (P = 0.19).

Conclusion: The clinical benefit of early, systematic rhythm control was not different between asymptomatic and symptomatic patients in EAST-AFNET 4. These results call for a shared decision discussing the benefits of rhythm control therapy in all patients with recently diagnosed AF and concomitant cardiovascular conditions (EAST-AFNET 4; ISRCTN04708680; NCT01288352; EudraCT2010-021258-20).

Keywords: Ablation; Antiarrhythmic drugs; Atrial fibrillation; Clinical trial; Rhythm control; Symptoms.

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Figures

Graphical Abstract
Graphical Abstract
Figure 1
Figure 1
Consort flow chart of the patients included in this analysis showing screening, randomization, treatment, and follow-up. Of all patients included into the EAST-AFNET 4 trial, 21 of the 2810 patients did not meet the inclusion criteria of early atrial fibrillation (diagnosed ≤1 year before enrolment) and cardiovascular conditions. After exclusion of 156 patients with missing baseline symptom status, 2633 patients were included into the analysis with randomization to early rhythm control (n = 1305) or usual care (n = 1328). Most of the patients assigned to early rhythm-control were initially treated with antiarrhythmic drugs, regardless of symptom status. After 2 years of follow-up, 242 of the 395 asymptomatic patients (59.3%) and 601 of the 910 symptomatic patients (64.8%) who had been randomly assigned to early rhythm control therapy were still receiving active rhythm-control therapy [atrial fibrillation ablation in 75/395 (19.0%) asymptomatic patients and in 176/910 (19.3%) symptomatic patients; P = 0.672] randomized to early rhythm control. This corresponds to ca 25% of patients randomized to early rhythm control and still in follow-up at 24 months.
Figure 2
Figure 2
Aalen–Johansen cumulative-incidence curves for the first primary outcome: (A) for patients with asymptomatic atrial fibrillation at baseline and (B) for patients with symptomatic atrial fibrillation at baseline. The first primary outcome was a composite of death from cardiovascular causes, stroke, or hospitalization with worsening of heart failure or acute coronary syndrome. The effect of early rhythm control on this outcome was almost identical in symptomatic and asymptomatic patients.
Figure 3
Figure 3
Change in atrial fibrillation symptoms between discharge from baseline and 24 months follow-up. There were no differences in symptom status at 24 months between randomized groups, irrespective of the presence of baseline symptoms (P = 0.1161). Symptoms improved without inter-group difference, illustrating the good adherence to protocol in patients randomized to usual care, which included symptom-directed rhythm control therapy to improve atrial fibrillation-related symptoms.
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