Genetically Targeted Therapy for the Prevention of Symptomatic Atrial Fibrillation in Patients With Heart Failure

Summary

This study is being done to compare the effects of bucindolol hydrochloride (bucindolol) to metoprolol succinate (Toprol-XL) on the recurrence of symptomatic atrial fibrillation/atrial flutter in patients with heart failure who have a specific genotype for the beta-1 adrenergic receptor.

Timeline

Start

2014-04

Primary completion

2017-12-28

Completion

2017-12-28

Publications

• Background Liggett SB, Mialet-Perez J, Thaneemit-Chen S, Weber SA, Greene SM, Hodne D, Nelson B, Morrison J, Domanski MJ, Wagoner LE, Abraham WT, Anderson JL, Carlquist JF, Krause-Steinrauf HJ, Lazzeroni LC, Port JD, Lavori PW, Bristow MR. A polymorphism within a conserved beta(1)-adrenergic receptor motif alters cardiac function and beta-blocker response in human heart failure. Proc Natl Acad Sci U S A. 2006 Jul 25;103(30):11288-93. doi: 10.1073/pnas.0509937103. Epub 2006 Jul 14.
• Background O'Connor CM, Fiuzat M, Carson PE, Anand IS, Plehn JF, Gottlieb SS, Silver MA, Lindenfeld J, Miller AB, White M, Walsh R, Nelson P, Medway A, Davis G, Robertson AD, Port JD, Carr J, Murphy GA, Lazzeroni LC, Abraham WT, Liggett SB, Bristow MR. Combinatorial pharmacogenetic interactions of bucindolol and beta1, alpha2C adrenergic receptor polymorphisms. PLoS One. 2012;7(10):e44324. doi: 10.1371/journal.pone.0044324. Epub 2012 Oct 10.
• Background Aleong RG, Sauer WH, Davis G, Murphy GA, Port JD, Anand IS, Fiuzat M, O'Connor CM, Abraham WT, Liggett SB, Bristow MR. Prevention of atrial fibrillation by bucindolol is dependent on the beta(1)389 Arg/Gly adrenergic receptor polymorphism. JACC Heart Fail. 2013 Aug;1(4):338-344. doi: 10.1016/j.jchf.2013.04.002.
• Background Kao DP, Davis G, Aleong R, O'Connor CM, Fiuzat M, Carson PE, Anand IS, Plehn JF, Gottlieb SS, Silver MA, Lindenfeld J, Miller AB, White M, Murphy GA, Sauer W, Bristow MR. Effect of bucindolol on heart failure outcomes and heart rate response in patients with reduced ejection fraction heart failure and atrial fibrillation. Eur J Heart Fail. 2013 Mar;15(3):324-33. doi: 10.1093/eurjhf/hfs181. Epub 2012 Dec 7.
• Carroll IA, Piccini JP, Steinberg BA, Tzou WS, Richards JC, DeMets DL, Bristow MR. Symptoms Burden as a Clinical Outcomes Assessment in Heart Failure Patients With Atrial Fibrillation. JACC Heart Fail. 2025 Apr;13(4):573-585. doi: 10.1016/j.jchf.2024.08.023. Epub 2024 Nov 20.
• 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; Genotype-Directed Comparative Effectiveness Trial of Bucindolol and Toprol-XL for Prevention of Atrial Fibrillation/Atrial Flutter in Patients with Heart Failure Trial Investigators*. Bucindolol Decreases Atrial Fibrillation Burden in Patients With Heart Failure and the ADRB1 Arg389Arg Genotype. Circ Arrhythm Electrophysiol. 2021 Aug;14(8):e009591. doi: 10.1161/CIRCEP.120.009591. Epub 2021 Jul 16.
• Piccini JP, Connolly SJ, Abraham WT, Healey JS, Steinberg BA, Al-Khalidi HR, Dignacco P, van Veldhuisen DJ, Sauer WH, White M, Wilton SB, Anand IS, Dufton C, Marshall DA, Aleong RG, Davis GW, Clark RL, Emery LL, Bristow MR. A genotype-directed comparative effectiveness trial of Bucindolol and metoprolol succinate for prevention of symptomatic atrial fibrillation/atrial flutter in patients with heart failure: Rationale and design of the GENETIC-AF trial. Am Heart J. 2018 May;199:51-58. doi: 10.1016/j.ahj.2017.12.001. Epub 2017 Dec 6.

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