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

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          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 CHA 2DS 2-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).

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          Most cited references26

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            2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation

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              A comparison of rate control and rhythm control in patients with atrial fibrillation.

              There are two approaches to the treatment of atrial fibrillation: one is cardioversion and treatment with antiarrhythmic drugs to maintain sinus rhythm, and the other is the use of rate-controlling drugs, allowing atrial fibrillation to persist. In both approaches, the use of anticoagulant drugs is recommended. We conducted a randomized, multicenter comparison of these two treatment strategies in patients with atrial fibrillation and a high risk of stroke or death. The primary end point was overall mortality. A total of 4060 patients (mean [+/-SD] age, 69.7+/-9.0 years) were enrolled in the study; 70.8 percent had a history of hypertension, and 38.2 percent had coronary artery disease. Of the 3311 patients with echocardiograms, the left atrium was enlarged in 64.7 percent and left ventricular function was depressed in 26.0 percent. There were 356 deaths among the patients assigned to rhythm-control therapy and 310 deaths among those assigned to rate-control therapy (mortality at five years, 23.8 percent and 21.3 percent, respectively; hazard ratio, 1.15 [95 percent confidence interval, 0.99 to 1.34]; P=0.08). More patients in the rhythm-control group than in the rate-control group were hospitalized, and there were more adverse drug effects in the rhythm-control group as well. In both groups, the majority of strokes occurred after warfarin had been stopped or when the international normalized ratio was subtherapeutic. Management of atrial fibrillation with the rhythm-control strategy offers no survival advantage over the rate-control strategy, and there are potential advantages, such as a lower risk of adverse drug effects, with the rate-control strategy. Anticoagulation should be continued in this group of high-risk patients. Copyright 2002 Massachusetts Medical Society
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                Author and article information

                Journal
                Eur Heart J
                Eur Heart J
                eurheartj
                European Heart Journal
                Oxford University Press
                0195-668X
                1522-9645
                21 March 2022
                27 August 2021
                27 August 2021
                : 43
                : 12 , Focus Issue on Arrhythmias
                : 1219-1230
                Affiliations
                [1 ] Asklepios Hospital St. Georg, Department of Cardiology and Internal intensive care medicine, Faculty of Medicine, Semmelweis University Campus Hamburg , Hamburg, Germany
                [2 ] DZHK (German Center for Cardiovascular Research), Partner Site Hamburg/Kiel/Luebeck , Berlin, Germany
                [3 ] Atrial Fibrillation Network (AFNET) , Münster, Germany
                [4 ] Department of Cardiology, University Heart and Vascular Center, University Medical Center Hamburg , Martinistraße 52, Hamburg 20246, Germany
                [5 ] Department of Cardiology, Odense University Hospital , Denmark
                [6 ] Department of Clinical Research, University of Southern Denmark , Odense, Denmark
                [7 ] Department of Cardiology II (Electrophysiology), University Hospital Münster , Germany
                [8 ] Cardiology Clinical Academic Group, Molecular and Clinical Sciences Research Institute, St. George’s University of London , UK
                [9 ] Department of Cardiology, Maastricht University Medical Center and Cardiovascular Research Institute Maastricht , Netherlands
                [10 ] St. Vincenz Hospital , Paderborn, Germany
                [11 ] Working Group of Molecular Electrophysiology, University Hospital Magdeburg , Germany
                [12 ] University Hospital Zurich , Zurich, Switzerland
                [13 ] Division of Cardiology, Medical University Department , Kantonsspital Aarau, Switzerland
                [14 ] University Hospital Antwerp and Antwerp University , Antwerp, Belgium
                [15 ] Institute for Clinical and Experimental Medicine , Prague, Czech Republic
                [16 ] Department of Cardiovascular Sciences, University of Leicester, National Institute for Health Research Leicester Biomedical Research Centre, Glenfield Hospital , Leicester, UK
                [17 ] Institute of Medical Biometry and Epidemiology, University Medical Center Hamburg , Eppendorf, Germany
                [18 ] Arrhythmia Center of the National Institute of Cardiology, Medical Division of Cardinal Stefan Wyszynski University in Warsaw , Warsaw, Poland
                [19 ] Department of Cardiology, Ospedale dell’Angelo , Venice, Italy
                [20 ] Heart Sector, Hygeia Hospitals Group , Athens, Greece
                [21 ] University of Groningen, University Medical Center Groningen , Groningen, Netherlands
                [22 ] Institute of Cardiovascular Sciences, University of Birmingham , Birmingham, UK
                Author notes
                Corresponding author. Tel: +49 40 7410 52438, Email: p.kirchhof@ 123456uke.de
                Author information
                https://orcid.org/0000-0001-9145-6887
                https://orcid.org/0000-0001-7574-8900
                https://orcid.org/0000-0001-5626-7749
                https://orcid.org/0000-0001-5965-0671
                https://orcid.org/0000-0001-7170-9509
                https://orcid.org/0000-0002-7998-7113
                https://orcid.org/0000-0003-2974-3142
                https://orcid.org/0000-0002-1881-0197
                Article
                ehab593
                10.1093/eurheartj/ehab593
                8934687
                34447995
                76ce4f9b-2dda-4828-91f9-ea6c6b1fb53d
                © The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 02 July 2021
                : 06 August 2021
                : 17 August 2021
                : 13 August 2021
                Page count
                Pages: 12
                Funding
                Funded by: AFNET, DZHK, EHRA, Deutsche Herzstiftung (DHS), Abbott Laboratories, and Sanofi;
                Funded by: European Union BigData@Heart;
                Award ID: EU IMI 116074
                Funded by: British Heart Foundation, DOI 10.13039/501100000274;
                Award ID: FS/13/43/30324
                Award ID: PG/17/30/32961
                Award ID: PG/20/22/35093
                Award ID: AA/18/2/34218
                Funded by: German Ministry of Education and Research;
                Award ID: 81Z1710103
                Funded by: Leducq Foundation, DOI 10.13039/501100001674;
                Funded by: European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme;
                Award ID: 648131
                Funded by: European Union’s Horizon 2020 research and innovation programme;
                Award ID: AFFECT-EU
                Award ID: 847770
                Funded by: German Center for Cardiovascular Research;
                Award ID: 81Z1710103
                Funded by: German Ministry of Research and Education;
                Award ID: BMBF 01ZX1408A
                Funded by: ERACoSysMed3;
                Award ID: 031L0239
                Categories
                Fast Track Clinical Research
                Editor's Choice
                AcademicSubjects/MED00200

                Cardiovascular Medicine
                atrial fibrillation,symptoms,rhythm control,ablation,antiarrhythmic drugs,clinical trial

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