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

Europace. 2024 May 4:euae121. doi: 10.1093/europace/euae121. Online ahead of print.

Authors

Andreas Rillig^{1

2}, Lars Eckardt^{3

4}, Katrin Borof¹, A John Camm⁵, Harry J G M Crijns⁶, Andreas Goette^{3

7

8}, Günter Breithardt^{3

4}, Marc D Lemoine^{1

2}, Andreas Metzner^{1

2}, Laura Rottner^{1

2}, Ulrich Schotten⁹, Eik Vettorazzi¹⁰, Karl Wegscheider^{2

3

10}, Antonia Zapf¹⁰, Hein Heidbuchel^{11

12

13}, Stephan Willems¹⁴, Larissa Fabritz^{1

2

3

15

16}, Renate B Schnabel^{1

2

3}, Christina Magnussen^{1

2}, Paulus Kirchhof^{1

2

3

16}

Affiliations

¹ Department of Cardiology, University Heart and Vascular Center, University Medical Center Hamburg-Eppendorf, Germany.
² German Center for Cardiovascular Research, Partner Site Hamburg/Luebeck/Kiel, Germany.
³ Atrial Fibrillation Network (AFNET), Münster, Germany.
⁴ Department of Cardiology II - Electrophysiology, University Hospital Münster, Germany.
⁵ Cardiology Clinical Academic Group, Molecular and Clinical Sciences Research Institute, St. George's University of London, UK.
⁶ Department of Cardiology, Maastricht University Medical Center and Cardiovascular Research Institute Maastricht, Netherlands.
⁷ St. Vincenz Hospital, Paderborn, Germany.
⁸ Working Group of Molecular Electrophysiology, University Hospital Magdeburg, Germany.
⁹ Dept. of Physiology, Maastricht University, The Netherlands.
¹⁰ Institute of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Germany.
¹¹ Department of Cardiology, Faculty of Medicine and Health Sciences, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium.
¹² Cardiovascular Research, GENCOR, Faculty of Medicine and Health Sciences, Antwerp University, Antwerp, Belgium.
¹³ Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium.
¹⁴ Asklepios Klinik St. Georg, Klinik für Kardiologie und internistische Intensivmedizin, Hamburg, Germany.
¹⁵ University Center of Cardiovascular Science, University Heart and Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Germany.
¹⁶ Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, UK.

PMID: 38702961
DOI: 10.1093/europace/euae121

Abstract

Background and aims: Clinical concerns exist about the potential proarrhythmic effects of the sodium channel blockers flecainide and propafenone (SCB) in patients with cardiovascular disease. SCB were used to deliver early rhythm control (ERC) therapy in EAST-AFNET 4.

Methods: 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 or acute coronary syndrome) during SCB-intake for ERC patients (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.

Results: Flecainide or propafenone was given to 689 patients (age 69 (8) years; CHA2DS2-VASc 3.2 (1); 177 with heart failure; 41 with prior myocardial infarction, CABG or PCI; 26 with left ventricular hypertrophy >15 mm; median therapy duration 1,153 [237, 1,828] days). The primary efficacy outcome occurred less often in patients treated with SCB (3/100 (99/3,316) patient-years) than in patients who never received SCB (SCBnever 4.9/100 (150/3,083) patient-years, p < 0.001). There were numerically fewer primary safety outcomes in patients receiving SCB (2.9/100 (96/3,359) patient-years) than in SCBnever patients (4.2/100 (135/3,220) 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 heart failure.

Clinical trial registration: ISRCTN04708680, NCT01288352, EudraCT2010-021258-20, www.easttrial.org.

Keywords: atrial fibrillation; coronary artery disease; early rhythm control; heart failure; sodium channel blocker; stable cardiovascular disease.

Associated data

ClinicalTrials.gov/NCT01288352