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

Stephan Willems; Katrin Borof; Axel Brandes; Günter Breithardt; A John Camm; Harry J G M Crijns; Lars Eckardt; Nele Gessler; Andreas Goette; Laurent M Haegeli; Hein Heidbuchel; Josef Kautzner; G André Ng; Renate B Schnabel; Anna Suling; Lukasz Szumowski; Sakis Themistoclakis; Panos Vardas; Isabelle C van Gelder; Karl Wegscheider; Paulus Kirchhof

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, Katrin Borof, Axel Brandes, Günter Breithardt, A John Camm, Harry J G M Crijns, Lars Eckardt, Nele Gessler, Andreas Goette, Laurent M Haegeli, Hein Heidbuchel, Josef Kautzner, G André Ng, Renate B Schnabel, Anna Suling, Lukasz Szumowski, Sakis Themistoclakis, Panos Vardas, Isabelle C van Gelder, Karl WegscheiderPaulus Kirchhof^*

^*Corresponding author for this work

Cardiovascular Sciences

Research output: Contribution to journal › Article › peer-review

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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 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).

Original language	English
Article number	ehab593
Pages (from-to)	1219–1230
Number of pages	12
Journal	European Heart Journal
Volume	43
Issue number	12
Early online date	27 Aug 2021
DOIs	https://doi.org/10.1093/eurheartj/ehab593
Publication status	Published - 21 Mar 2022

Bibliographical note

Keywords

Atrial fibrillation
Symptoms
Rhythm control
Ablation
Antiarrhythmic drugs
Clinical trial

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10.1093/eurheartj/ehab593Licence: Creative Commons: Attribution (CC BY)

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BHF Research Accelerator Award
Bicknell, R. (Co-Investigator), Watson, S. (Co-Investigator), Rainger, E. (Co-Investigator), Senis, Y. (Co-Investigator), Fabritz, L. (Co-Investigator) & Kirchhof, P. (Principal Investigator)
British Heart Foundation
1/04/19 → 30/09/24
Project: Research
Impact of chronic intermittent hypoxia on atrial resting membrane potential and Na 1.5 channel function: A new mechanism for causing atrial fibrillation
Kirchhof, P. (Principal Investigator) & Holmes, A. (Co-Investigator)
British Heart Foundation
1/10/17 → 18/07/21
Project: Research
Understanding the function of PITX2 in the adult left atrium
Kirchhof, P. (Principal Investigator) & Fabritz, L. (Co-Investigator)
British Heart Foundation
4/11/13 → 3/11/18
Project: Research

Cite this

Willems, S., Borof, K., Brandes, A., Breithardt, G., Camm, A. J., Crijns, H. J. G. M., Eckardt, L., Gessler, N., Goette, A., Haegeli, L. M., Heidbuchel, H., Kautzner, J., Ng, G. A., Schnabel, R. B., Suling, A., Szumowski, L., Themistoclakis, S., Vardas, P., van Gelder, I. C., ... Kirchhof, P. (2022). Systematic, early rhythm control strategy for atrial fibrillation in patients with or without symptoms: the EAST-AFNET 4 trial. European Heart Journal, 43(12), 1219–1230. Article ehab593. https://doi.org/10.1093/eurheartj/ehab593

@article{462ccba5842843a19ac9ade392a01a14,

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

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 = "Atrial fibrillation, Symptoms, Rhythm control, Ablation, Antiarrhythmic drugs, Clinical trial",

author = "Stephan Willems and Katrin Borof and Axel Brandes and G{\"u}nter Breithardt and Camm, {A John} and Crijns, {Harry J G M} and Lars Eckardt and Nele Gessler and Andreas Goette and Haegeli, {Laurent M} and Hein Heidbuchel and Josef Kautzner and Ng, {G Andr{\'e}} and Schnabel, {Renate B} and Anna Suling and Lukasz Szumowski and Sakis Themistoclakis and Panos Vardas and {van Gelder}, {Isabelle C} and Karl Wegscheider and Paulus Kirchhof",

note = "{\textcopyright} The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.",

year = "2022",

month = mar,

day = "21",

doi = "10.1093/eurheartj/ehab593",

language = "English",

volume = "43",

pages = "1219–1230",

journal = "European Heart Journal",

issn = "0195-668X",

publisher = "Oxford University Press",

number = "12",

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Willems, S, Borof, K, Brandes, A, Breithardt, G, Camm, AJ, Crijns, HJGM, Eckardt, L, Gessler, N, Goette, A, Haegeli, LM, Heidbuchel, H, Kautzner, J, Ng, GA, Schnabel, RB, Suling, A, Szumowski, L, Themistoclakis, S, Vardas, P, van Gelder, IC, Wegscheider, K & Kirchhof, P 2022, 'Systematic, early rhythm control strategy for atrial fibrillation in patients with or without symptoms: the EAST-AFNET 4 trial', European Heart Journal, vol. 43, no. 12, ehab593, pp. 1219–1230. https://doi.org/10.1093/eurheartj/ehab593

TY - JOUR

T1 - Systematic, early rhythm control strategy for atrial fibrillation in patients with or without symptoms

T2 - the EAST-AFNET 4 trial

AU - Willems, Stephan

AU - Borof, Katrin

AU - Brandes, Axel

AU - Breithardt, Günter

AU - Camm, A John

AU - Crijns, Harry J G M

AU - Eckardt, Lars

AU - Gessler, Nele

AU - Goette, Andreas

AU - Haegeli, Laurent M

AU - Heidbuchel, Hein

AU - Kautzner, Josef

AU - Ng, G André

AU - Schnabel, Renate B

AU - Suling, Anna

AU - Szumowski, Lukasz

AU - Themistoclakis, Sakis

AU - Vardas, Panos

AU - van Gelder, Isabelle C

AU - Wegscheider, Karl

AU - Kirchhof, Paulus

PY - 2022/3/21

Y1 - 2022/3/21

N2 - 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).

AB - 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).

KW - Atrial fibrillation

KW - Symptoms

KW - Rhythm control

KW - Ablation

KW - Antiarrhythmic drugs

KW - Clinical trial

U2 - 10.1093/eurheartj/ehab593

DO - 10.1093/eurheartj/ehab593

M3 - Article

C2 - 34447995

SN - 0195-668X

VL - 43

SP - 1219

EP - 1230

JO - European Heart Journal

JF - European Heart Journal

IS - 12

M1 - ehab593

ER -

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

Abstract

Bibliographical note

Keywords

Access to Document

Fingerprint

Projects

BHF Research Accelerator Award

Impact of chronic intermittent hypoxia on atrial resting membrane potential and Na 1.5 channel function: A new mechanism for causing atrial fibrillation

Understanding the function of PITX2 in the adult left atrium

Cite this