Pharmacogenomics of Bucindolol in Atrial Fibrillation and Heart Failure
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Purpose of Review
We explore the pharmacogenomics of the beta-blocker bucindolol by discussing relevant beta-1 adrenergic receptor (ADRB1) polymorphisms and recent beta-blocker studies. Through this, we will understand how bucindolol may help patients with atrial fibrillation and heart failure with reduced ejection fraction (AF-HFrEF), which carries poor prognosis.
Retrospective study of the Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training trial revealed the interaction between the optimal beta-blocker dose and the ADRB1 Arg389 genotype for HFrEF clinical outcomes. Further, a combinatorial genotype analysis in the Beta-Blocker Evaluation of Survival Trial showed that the Arg389Arg genotype, but not the Gly carrier, was associated with 40% lower mortality risk with bucindolol. Finally, the AF-HFrEF subgroup with the ADRB1 Arg389Arg genotype had greater heart rate reduction and suggestion for mortality benefit.
Therapeutic response to beta-blockers varies by beta-blocker mechanism, ADRB1 Arg389 genotype, and clinical setting (AF, HFrEF, AF-HFrEF). The ongoing trial A Genotype-Directed Comparative Effectiveness Trial of Bucindolol and Toprol-XL for Prevention of Symptomatic Atrial Fibrillation/Atrial Flutter in Patients with Heart Failure prospectively identifies AF-HFrEF patients with favorable genotype for bucindolol to prevent AF recurrence.
KeywordsPharmacogenomics Bucindolol Heart failure Atrial fibrillation
Compliance with Ethical Standards
Conflict of Interest
Kishan S. Parikh declares no conflict of interest. Jonathan P. Piccini has received grants from ARCA Biopharma and Johnson & Johnson, Boston Scientific, ResMed, Gilead, St Jude Medical, and Spectranetics. Dr. Piccini is also a consultant for Amgen, Spectranetics, Medtronic, Allergan, and Janssen Pharmaceuticals.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
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