Safety and efficacy of long-term sodium channel blocker therapy for early rhythm control: the EAST-AFNET 4 trial

Andreas Rillig; Lars Eckardt; Katrin Borof; A John Camm; Harry J G M Crijns; Andreas Goette; Günter Breithardt; Marc D Lemoine; Andreas Metzner; Laura Rottner; Ulrich Schotten; Eik Vettorazzi; Karl Wegscheider; Antonia Zapf; Hein Heidbuchel; Stephan Willems; Larissa Fabritz; Renate B Schnabel; Christina Magnussen; Paulus Kirchhof

doi:10.1093/europace/euae121

Safety and efficacy of long-term sodium channel blocker therapy for early rhythm control: the EAST-AFNET 4 trial

Andreas Rillig, Lars Eckardt, Katrin Borof, A John Camm, Harry J G M Crijns, Andreas Goette, Günter Breithardt, Marc D Lemoine, Andreas Metzner, Laura Rottner, Ulrich Schotten, Eik Vettorazzi, Karl Wegscheider, Antonia Zapf, Hein Heidbuchel, Stephan Willems, Larissa Fabritz, Renate B Schnabel, Christina Magnussen, Paulus Kirchhof^*

^*Corresponding author for this work

Cardiovascular Sciences

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

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Abstract

Aims: Clinical concerns exist about the potential proarrhythmic effects of the sodium channel blockers (SCBs) flecainide and propafenone in patients with cardiovascular disease. Sodium channel blockers were used to deliver early rhythm control (ERC) therapy in EAST-AFNET 4.
Methods and results: We analysed the primary safety outcome (death, stroke, or serious adverse events related to rhythm control therapy) and primary efficacy outcome (cardiovascular death, stroke, and hospitalization for worsening of heart failure (HF) or acute coronary syndrome) during SCB intake for patients with ERC (n = 1395) in EAST-AFNET 4. The protocol discouraged flecainide and propafenone in patients with reduced left ventricular ejection fraction and suggested stopping therapy upon QRS prolongation >25% on therapy. Flecainide or propafenone was given to 689 patients [age 69 (8) years; CHA₂DS₂-VASc 3.2 (1); 177 with HF; 41 with prior myocardial infarction, coronary artery bypass graft, or percutaneous coronary intervention; 26 with left ventricular hypertrophy >15 mm; median therapy duration 1153 [237, 1828] days]. The primary efficacy outcome occurred less often in patients treated with SCB [3/100 (99/3316) patient-years] than in patients who never received SCB [SCB^never 4.9/100 (150/3083) patient-years, P < 0.001]. There were numerically fewer primary safety outcomes in patients receiving SCB [2.9/100 (96/3359) patient-years] than in SCBnever patients [4.2/100 (135/3220) patient-years, adjusted P = 0.015]. Sinus rhythm at 2 years was similar between groups [SCB 537/610 (88); SCB^never 472/579 (82)].
Conclusion: Long-term therapy with flecainide or propafenone appeared to be safe in the EAST-AFNET 4 trial to deliver effective ERC therapy, including in selected patients with stable cardiovascular disease such as coronary artery disease and stable HF.
Clinical Trial Registration ISRCTN04708680, NCT01288352, EudraCT2010-021258-20, www.easttrial.org

Original language	English
Article number	euae121
Number of pages	14
Journal	Europace
Volume	26
Issue number	6
Early online date	4 May 2024
DOIs	https://doi.org/10.1093/europace/euae121
Publication status	Published - 6 Jun 2024

Keywords

Coronary artery disease
Atrial fibrillation
Early rhythm control
Heart failure
Stable cardiovascular disease
Sodium channel blocker

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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MAESTRIA: Machine Learning Artificial Intelligence Early Detection Stroke Atrial Fibrillation
Kirchhof, P., Gkoutos, G. & Fabritz, L.
European Commission
1/03/21 → 28/02/26
Project: EU
Defining clusters of patients with atrial fibrillation at risk of heart failure and death
Kirchhof, P. & Gkoutos, G.
British Heart Foundation
1/07/20 → 30/06/21
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. & Holmes, A.
British Heart Foundation
1/10/17 → 18/07/21
Project: Research
H2020_COLLAB(IMI-JU)_BIGDATA@HEART
Kotecha, D. & Kirchhof, P.
European Commission
1/03/17 → 28/02/23
Project: Research
H2020_COLLAB_CATCH ME_(LEAD)
Kirchhof, P., Fabritz, L., Hemming, K. & Deeks, J.
European Commission
1/05/15 → 30/04/19
Project: EU
Understanding the function of PITX2 in the adult left atrium
Kirchhof, P. & Fabritz, L.
British Heart Foundation
4/11/13 → 3/11/18
Project: Research

Cite this

Rillig, A., Eckardt, L., Borof, K., Camm, A. J., Crijns, H. J. G. M., Goette, A., Breithardt, G., Lemoine, M. D., Metzner, A., Rottner, L., Schotten, U., Vettorazzi, E., Wegscheider, K., Zapf, A., Heidbuchel, H., Willems, S., Fabritz, L., Schnabel, R. B., Magnussen, C., & Kirchhof, P. (2024). Safety and efficacy of long-term sodium channel blocker therapy for early rhythm control: the EAST-AFNET 4 trial. Europace, 26(6), Article euae121. https://doi.org/10.1093/europace/euae121

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title = "Safety and efficacy of long-term sodium channel blocker therapy for early rhythm control: the EAST-AFNET 4 trial",

abstract = "Aims: Clinical concerns exist about the potential proarrhythmic effects of the sodium channel blockers (SCBs) flecainide and propafenone in patients with cardiovascular disease. Sodium channel blockers were used to deliver early rhythm control (ERC) therapy in EAST-AFNET 4. Methods and results: We analysed the primary safety outcome (death, stroke, or serious adverse events related to rhythm control therapy) and primary efficacy outcome (cardiovascular death, stroke, and hospitalization for worsening of heart failure (HF) or acute coronary syndrome) during SCB intake for patients with ERC (n = 1395) in EAST-AFNET 4. The protocol discouraged flecainide and propafenone in patients with reduced left ventricular ejection fraction and suggested stopping therapy upon QRS prolongation >25% on therapy. Flecainide or propafenone was given to 689 patients [age 69 (8) years; CHA2DS2-VASc 3.2 (1); 177 with HF; 41 with prior myocardial infarction, coronary artery bypass graft, or percutaneous coronary intervention; 26 with left ventricular hypertrophy >15 mm; median therapy duration 1153 [237, 1828] days]. The primary efficacy outcome occurred less often in patients treated with SCB [3/100 (99/3316) patient-years] than in patients who never received SCB [SCBnever 4.9/100 (150/3083) patient-years, P < 0.001]. There were numerically fewer primary safety outcomes in patients receiving SCB [2.9/100 (96/3359) patient-years] than in SCBnever patients [4.2/100 (135/3220) patient-years, adjusted P = 0.015]. Sinus rhythm at 2 years was similar between groups [SCB 537/610 (88); SCBnever 472/579 (82)]. Conclusion: Long-term therapy with flecainide or propafenone appeared to be safe in the EAST-AFNET 4 trial to deliver effective ERC therapy, including in selected patients with stable cardiovascular disease such as coronary artery disease and stable HF. Clinical Trial Registration ISRCTN04708680, NCT01288352, EudraCT2010-021258-20, www.easttrial.org",

keywords = "Coronary artery disease, Atrial fibrillation, Early rhythm control, Heart failure, Stable cardiovascular disease, Sodium channel blocker",

author = "Andreas Rillig and Lars Eckardt and Katrin Borof and Camm, {A John} and Crijns, {Harry J G M} and Andreas Goette and G{\"u}nter Breithardt and Lemoine, {Marc D} and Andreas Metzner and Laura Rottner and Ulrich Schotten and Eik Vettorazzi and Karl Wegscheider and Antonia Zapf and Hein Heidbuchel and Stephan Willems and Larissa Fabritz and Schnabel, {Renate B} and Christina Magnussen and Paulus Kirchhof",

year = "2024",

month = jun,

day = "6",

doi = "10.1093/europace/euae121",

language = "English",

volume = "26",

journal = "Europace",

issn = "1099-5129",

publisher = "Oxford University Press",

number = "6",

}

Rillig, A, Eckardt, L, Borof, K, Camm, AJ, Crijns, HJGM, Goette, A, Breithardt, G, Lemoine, MD, Metzner, A, Rottner, L, Schotten, U, Vettorazzi, E, Wegscheider, K, Zapf, A, Heidbuchel, H, Willems, S, Fabritz, L, Schnabel, RB, Magnussen, C & Kirchhof, P 2024, 'Safety and efficacy of long-term sodium channel blocker therapy for early rhythm control: the EAST-AFNET 4 trial', Europace, vol. 26, no. 6, euae121. https://doi.org/10.1093/europace/euae121

TY - JOUR

T1 - Safety and efficacy of long-term sodium channel blocker therapy for early rhythm control

T2 - the EAST-AFNET 4 trial

AU - Rillig, Andreas

AU - Eckardt, Lars

AU - Borof, Katrin

AU - Camm, A John

AU - Crijns, Harry J G M

AU - Goette, Andreas

AU - Breithardt, Günter

AU - Lemoine, Marc D

AU - Metzner, Andreas

AU - Rottner, Laura

AU - Schotten, Ulrich

AU - Vettorazzi, Eik

AU - Wegscheider, Karl

AU - Zapf, Antonia

AU - Heidbuchel, Hein

AU - Willems, Stephan

AU - Fabritz, Larissa

AU - Schnabel, Renate B

AU - Magnussen, Christina

AU - Kirchhof, Paulus

PY - 2024/6/6

Y1 - 2024/6/6

N2 - Aims: Clinical concerns exist about the potential proarrhythmic effects of the sodium channel blockers (SCBs) flecainide and propafenone in patients with cardiovascular disease. Sodium channel blockers were used to deliver early rhythm control (ERC) therapy in EAST-AFNET 4. Methods and results: We analysed the primary safety outcome (death, stroke, or serious adverse events related to rhythm control therapy) and primary efficacy outcome (cardiovascular death, stroke, and hospitalization for worsening of heart failure (HF) or acute coronary syndrome) during SCB intake for patients with ERC (n = 1395) in EAST-AFNET 4. The protocol discouraged flecainide and propafenone in patients with reduced left ventricular ejection fraction and suggested stopping therapy upon QRS prolongation >25% on therapy. Flecainide or propafenone was given to 689 patients [age 69 (8) years; CHA2DS2-VASc 3.2 (1); 177 with HF; 41 with prior myocardial infarction, coronary artery bypass graft, or percutaneous coronary intervention; 26 with left ventricular hypertrophy >15 mm; median therapy duration 1153 [237, 1828] days]. The primary efficacy outcome occurred less often in patients treated with SCB [3/100 (99/3316) patient-years] than in patients who never received SCB [SCBnever 4.9/100 (150/3083) patient-years, P < 0.001]. There were numerically fewer primary safety outcomes in patients receiving SCB [2.9/100 (96/3359) patient-years] than in SCBnever patients [4.2/100 (135/3220) patient-years, adjusted P = 0.015]. Sinus rhythm at 2 years was similar between groups [SCB 537/610 (88); SCBnever 472/579 (82)]. Conclusion: Long-term therapy with flecainide or propafenone appeared to be safe in the EAST-AFNET 4 trial to deliver effective ERC therapy, including in selected patients with stable cardiovascular disease such as coronary artery disease and stable HF. Clinical Trial Registration ISRCTN04708680, NCT01288352, EudraCT2010-021258-20, www.easttrial.org

AB - Aims: Clinical concerns exist about the potential proarrhythmic effects of the sodium channel blockers (SCBs) flecainide and propafenone in patients with cardiovascular disease. Sodium channel blockers were used to deliver early rhythm control (ERC) therapy in EAST-AFNET 4. Methods and results: We analysed the primary safety outcome (death, stroke, or serious adverse events related to rhythm control therapy) and primary efficacy outcome (cardiovascular death, stroke, and hospitalization for worsening of heart failure (HF) or acute coronary syndrome) during SCB intake for patients with ERC (n = 1395) in EAST-AFNET 4. The protocol discouraged flecainide and propafenone in patients with reduced left ventricular ejection fraction and suggested stopping therapy upon QRS prolongation >25% on therapy. Flecainide or propafenone was given to 689 patients [age 69 (8) years; CHA2DS2-VASc 3.2 (1); 177 with HF; 41 with prior myocardial infarction, coronary artery bypass graft, or percutaneous coronary intervention; 26 with left ventricular hypertrophy >15 mm; median therapy duration 1153 [237, 1828] days]. The primary efficacy outcome occurred less often in patients treated with SCB [3/100 (99/3316) patient-years] than in patients who never received SCB [SCBnever 4.9/100 (150/3083) patient-years, P < 0.001]. There were numerically fewer primary safety outcomes in patients receiving SCB [2.9/100 (96/3359) patient-years] than in SCBnever patients [4.2/100 (135/3220) patient-years, adjusted P = 0.015]. Sinus rhythm at 2 years was similar between groups [SCB 537/610 (88); SCBnever 472/579 (82)]. Conclusion: Long-term therapy with flecainide or propafenone appeared to be safe in the EAST-AFNET 4 trial to deliver effective ERC therapy, including in selected patients with stable cardiovascular disease such as coronary artery disease and stable HF. Clinical Trial Registration ISRCTN04708680, NCT01288352, EudraCT2010-021258-20, www.easttrial.org

KW - Coronary artery disease

KW - Atrial fibrillation

KW - Early rhythm control

KW - Heart failure

KW - Stable cardiovascular disease

KW - Sodium channel blocker

U2 - 10.1093/europace/euae121

DO - 10.1093/europace/euae121

M3 - Article

SN - 1099-5129

VL - 26

JO - Europace

JF - Europace

IS - 6

M1 - euae121

ER -

Safety and efficacy of long-term sodium channel blocker therapy for early rhythm control: the EAST-AFNET 4 trial

Abstract

Keywords

UN SDGs

Access to Document

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Projects

MAESTRIA: Machine Learning Artificial Intelligence Early Detection Stroke Atrial Fibrillation

Defining clusters of patients with atrial fibrillation at risk of heart failure and death

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

H2020_COLLAB(IMI-JU)_BIGDATA@HEART

H2020_COLLAB_CATCH ME_(LEAD)

Understanding the function of PITX2 in the adult left atrium

Cite this