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).

Arrhythmia Center of the National Institute of Cardiology Medical Division of Cardinal Stefan Wyszynski University in Warsaw Warsaw Poland

Asklepios Hospital St Georg Department of Cardiology and Internal intensive care medicine Faculty of Medicine Semmelweis University Campus Hamburg Hamburg Germany

Atrial Fibrillation Network Münster Germany

Cardiology Clinical Academic Group Molecular and Clinical Sciences Research Institute St George's University of London UK

Department of Cardiology 2 University Hospital Münster Germany

Department of Cardiology Maastricht University Medical Center and Cardiovascular Research Institute Maastricht Netherlands

Department of Cardiology Odense University Hospital Denmark

Department of Cardiology Ospedale dell'Angelo Venice Italy

Department of Cardiology University Heart and Vascular Center University Medical Center Hamburg Martinistraße 52 Hamburg 20246 Germany

Department of Cardiovascular Sciences University of Leicester National Institute for Health Research Leicester Biomedical Research Centre Glenfield Hospital Leicester UK

Department of Clinical Research University of Southern Denmark Odense Denmark

Division of Cardiology Medical University Department Kantonsspital Aarau Switzerland

DZHK Partner Site Hamburg Kiel Luebeck Berlin Germany

Heart Sector Hygeia Hospitals Group Athens Greece

Institute for Clinical and Experimental Medicine Prague Czech Republic

Institute of Cardiovascular Sciences University of Birmingham Birmingham UK

Institute of Medical Biometry and Epidemiology University Medical Center Hamburg Eppendorf Germany

St Vincenz Hospital Paderborn Germany

University Hospital Antwerp and Antwerp University Antwerp Belgium

University Hospital Zurich Zurich Switzerland

University of Groningen University Medical Center Groningen Groningen Netherlands

Working Group of Molecular Electrophysiology University Hospital Magdeburg Germany

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ClinicalTrials.gov
NCT01288352

ISRCTN
ISRCTN04708680

EudraCT
2010-021258-20