Bucindolol Decreases Atrial Fibrillation Burden in Patients With Heart Failure and the ADRB1 Arg389Arg Genotype

Jonathan P Piccini; Christopher Dufton; Ian A Carroll; Jeff S Healey; William T Abraham; Yaariv Khaykin; Ryan Aleong; Steven K Krueger; William H Sauer; Stephen B Wilton; Michiel Rienstra; Dirk J van Veldhuisen; Inder S Anand; Michel White; A John Camm; Paul D Ziegler; Debra Marshall; Michael R Bristow; Stuart J Connolly

doi:10.1161/CIRCEP.120.009591

Bucindolol Decreases Atrial Fibrillation Burden in Patients With Heart Failure and the ADRB1 Arg389Arg Genotype

Jonathan P Piccini^*, Christopher Dufton, Ian A Carroll, Jeff S Healey, William T Abraham, Yaariv Khaykin, Ryan Aleong, Steven K Krueger, William H Sauer, Stephen B Wilton, Michiel Rienstra, Dirk J van Veldhuisen, Inder S Anand, Michel White, A John Camm, Paul D Ziegler, Debra Marshall, Michael R Bristow, Stuart J Connolly

^*Corresponding author for this work

Cardiovascular Centre (CVC)

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

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Abstract

Background: Bucindolol is a genetically targeted beta-blocker/mild vasodilator with the unique pharmacological properties of sympatholysis and ADRB1 Arg389 receptor inverse agonism. In the GENETIC-AF trial (Genotype-Directed Comparative Effectiveness Trial of Bucindolol and Toprol-XL for the Prevention of Symptomatic Atrial Fibrillation/Atrial Flutter in Patients With Heart Failure) conducted in a genetically defined heart failure population at high risk for recurrent atrial fibrillation (AF), similar results were observed for bucindolol and metoprolol succinate for the primary end point of time to first AF event; however, AF burden and other rhythm control measures were not analyzed.

Methods: The prevalence of ECGs in normal sinus rhythm, AF interventions for rhythm control (cardioversion, ablation, and antiarrhythmic drugs) and biomarkers were evaluated in the overall population entering efficacy follow-up (N=257). AF burden was evaluated for 24 weeks in the device substudy (N=67).

Results: In 257 patients with heart failure, the mean age was 65.6 +/- 10.0 years, 18% were female, mean left ventricular ejection fraction was 36%, and 51% had persistent AF. Cumulative 24-week AF burden was 24.4% (95% CI, 18.5-30.2) for bucindolol and 36.7% (95% CI, 30.0-43.5) for metoprolol (33% reduction, P

Conclusions: Compared with metoprolol, bucindolol reduced AF burden, improved maintenance of sinus rhythm, and lowered the need for additional rhythm control interventions in patients with heart failure and the ADRB1 Arg389Arg genotype.

Original language	English
Article number	009591
Number of pages	12
Journal	Circulation. Arrhythmia and Electrophysiology
Volume	14
Issue number	8
Early online date	16-Jul-2021
DOIs	https://doi.org/10.1161/CIRCEP.120.009591
Publication status	Published - Aug-2021

Keywords

atrial fibrillation
atrial flutter
bucindolol
heart failure
metoprolol
RISK
DRONEDARONE
TRIAL

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Bucindolol Decreases Atrial Fibrillation Burden in Patients With Heart Failure and the ADRB1 Arg389Arg GenotypeFinal publisher's version, 1.2 MBLicence: Taverne

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Piccini, J. P., Dufton, C., Carroll, I. A., Healey, J. S., Abraham, W. T., Khaykin, Y., Aleong, R., Krueger, S. K., Sauer, W. H., Wilton, S. B., Rienstra, M., van Veldhuisen, D. J., Anand, I. S., White, M., Camm, A. J., Ziegler, P. D., Marshall, D., Bristow, M. R., & Connolly, S. J. (2021). Bucindolol Decreases Atrial Fibrillation Burden in Patients With Heart Failure and the ADRB1 Arg389Arg Genotype. Circulation. Arrhythmia and Electrophysiology, 14(8), Article 009591. https://doi.org/10.1161/CIRCEP.120.009591

@article{e4da658bc78f4c9fa6ea3c34cd1b9426,

title = "Bucindolol Decreases Atrial Fibrillation Burden in Patients With Heart Failure and the ADRB1 Arg389Arg Genotype",

abstract = "Background: Bucindolol is a genetically targeted beta-blocker/mild vasodilator with the unique pharmacological properties of sympatholysis and ADRB1 Arg389 receptor inverse agonism. In the GENETIC-AF trial (Genotype-Directed Comparative Effectiveness Trial of Bucindolol and Toprol-XL for the Prevention of Symptomatic Atrial Fibrillation/Atrial Flutter in Patients With Heart Failure) conducted in a genetically defined heart failure population at high risk for recurrent atrial fibrillation (AF), similar results were observed for bucindolol and metoprolol succinate for the primary end point of time to first AF event; however, AF burden and other rhythm control measures were not analyzed.Methods: The prevalence of ECGs in normal sinus rhythm, AF interventions for rhythm control (cardioversion, ablation, and antiarrhythmic drugs) and biomarkers were evaluated in the overall population entering efficacy follow-up (N=257). AF burden was evaluated for 24 weeks in the device substudy (N=67).Results: In 257 patients with heart failure, the mean age was 65.6 +/- 10.0 years, 18% were female, mean left ventricular ejection fraction was 36%, and 51% had persistent AF. Cumulative 24-week AF burden was 24.4% (95% CI, 18.5-30.2) for bucindolol and 36.7% (95% CI, 30.0-43.5) for metoprolol (33% reduction, PConclusions: Compared with metoprolol, bucindolol reduced AF burden, improved maintenance of sinus rhythm, and lowered the need for additional rhythm control interventions in patients with heart failure and the ADRB1 Arg389Arg genotype.",

keywords = "atrial fibrillation, atrial flutter, bucindolol, heart failure, metoprolol, RISK, DRONEDARONE, TRIAL",

author = "Piccini, {Jonathan P} and Christopher Dufton and Carroll, {Ian A} and Healey, {Jeff S} and Abraham, {William T} and Yaariv Khaykin and Ryan Aleong and Krueger, {Steven K} and Sauer, {William H} and Wilton, {Stephen B} and Michiel Rienstra and {van Veldhuisen}, {Dirk J} and Anand, {Inder S} and Michel White and Camm, {A John} and Ziegler, {Paul D} and Debra Marshall and Bristow, {Michael R} and Connolly, {Stuart J}",

year = "2021",

month = aug,

doi = "10.1161/CIRCEP.120.009591",

language = "English",

volume = "14",

journal = "Circulation. Arrhythmia and Electrophysiology",

issn = "1941-3149",

publisher = "LIPPINCOTT WILLIAMS & WILKINS",

number = "8",

}

Piccini, JP, Dufton, C, Carroll, IA, Healey, JS, Abraham, WT, Khaykin, Y, Aleong, R, Krueger, SK, Sauer, WH, Wilton, SB, Rienstra, M , van Veldhuisen, DJ, Anand, IS, White, M, Camm, AJ, Ziegler, PD, Marshall, D, Bristow, MR & Connolly, SJ 2021, 'Bucindolol Decreases Atrial Fibrillation Burden in Patients With Heart Failure and the ADRB1 Arg389Arg Genotype', Circulation. Arrhythmia and Electrophysiology, vol. 14, no. 8, 009591. https://doi.org/10.1161/CIRCEP.120.009591

TY - JOUR

T1 - Bucindolol Decreases Atrial Fibrillation Burden in Patients With Heart Failure and the ADRB1 Arg389Arg Genotype

AU - Piccini, Jonathan P

AU - Dufton, Christopher

AU - Carroll, Ian A

AU - Healey, Jeff S

AU - Abraham, William T

AU - Khaykin, Yaariv

AU - Aleong, Ryan

AU - Krueger, Steven K

AU - Sauer, William H

AU - Wilton, Stephen B

AU - Rienstra, Michiel

AU - van Veldhuisen, Dirk J

AU - Anand, Inder S

AU - White, Michel

AU - Camm, A John

AU - Ziegler, Paul D

AU - Marshall, Debra

AU - Bristow, Michael R

AU - Connolly, Stuart J

PY - 2021/8

Y1 - 2021/8

N2 - Background: Bucindolol is a genetically targeted beta-blocker/mild vasodilator with the unique pharmacological properties of sympatholysis and ADRB1 Arg389 receptor inverse agonism. In the GENETIC-AF trial (Genotype-Directed Comparative Effectiveness Trial of Bucindolol and Toprol-XL for the Prevention of Symptomatic Atrial Fibrillation/Atrial Flutter in Patients With Heart Failure) conducted in a genetically defined heart failure population at high risk for recurrent atrial fibrillation (AF), similar results were observed for bucindolol and metoprolol succinate for the primary end point of time to first AF event; however, AF burden and other rhythm control measures were not analyzed.Methods: The prevalence of ECGs in normal sinus rhythm, AF interventions for rhythm control (cardioversion, ablation, and antiarrhythmic drugs) and biomarkers were evaluated in the overall population entering efficacy follow-up (N=257). AF burden was evaluated for 24 weeks in the device substudy (N=67).Results: In 257 patients with heart failure, the mean age was 65.6 +/- 10.0 years, 18% were female, mean left ventricular ejection fraction was 36%, and 51% had persistent AF. Cumulative 24-week AF burden was 24.4% (95% CI, 18.5-30.2) for bucindolol and 36.7% (95% CI, 30.0-43.5) for metoprolol (33% reduction, PConclusions: Compared with metoprolol, bucindolol reduced AF burden, improved maintenance of sinus rhythm, and lowered the need for additional rhythm control interventions in patients with heart failure and the ADRB1 Arg389Arg genotype.

AB - Background: Bucindolol is a genetically targeted beta-blocker/mild vasodilator with the unique pharmacological properties of sympatholysis and ADRB1 Arg389 receptor inverse agonism. In the GENETIC-AF trial (Genotype-Directed Comparative Effectiveness Trial of Bucindolol and Toprol-XL for the Prevention of Symptomatic Atrial Fibrillation/Atrial Flutter in Patients With Heart Failure) conducted in a genetically defined heart failure population at high risk for recurrent atrial fibrillation (AF), similar results were observed for bucindolol and metoprolol succinate for the primary end point of time to first AF event; however, AF burden and other rhythm control measures were not analyzed.Methods: The prevalence of ECGs in normal sinus rhythm, AF interventions for rhythm control (cardioversion, ablation, and antiarrhythmic drugs) and biomarkers were evaluated in the overall population entering efficacy follow-up (N=257). AF burden was evaluated for 24 weeks in the device substudy (N=67).Results: In 257 patients with heart failure, the mean age was 65.6 +/- 10.0 years, 18% were female, mean left ventricular ejection fraction was 36%, and 51% had persistent AF. Cumulative 24-week AF burden was 24.4% (95% CI, 18.5-30.2) for bucindolol and 36.7% (95% CI, 30.0-43.5) for metoprolol (33% reduction, PConclusions: Compared with metoprolol, bucindolol reduced AF burden, improved maintenance of sinus rhythm, and lowered the need for additional rhythm control interventions in patients with heart failure and the ADRB1 Arg389Arg genotype.

KW - atrial fibrillation

KW - atrial flutter

KW - bucindolol

KW - heart failure

KW - metoprolol

KW - RISK

KW - DRONEDARONE

KW - TRIAL

U2 - 10.1161/CIRCEP.120.009591

DO - 10.1161/CIRCEP.120.009591

M3 - Article

C2 - 34270905

SN - 1941-3149

VL - 14

JO - Circulation. Arrhythmia and Electrophysiology

JF - Circulation. Arrhythmia and Electrophysiology

IS - 8

M1 - 009591

ER -

Bucindolol Decreases Atrial Fibrillation Burden in Patients With Heart Failure and the ADRB1 Arg389Arg Genotype

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