Pharmacogenomics of Bucindolol in Atrial Fibrillation and Heart Failure.

Published

Journal Article (Review)

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. RECENT FINDINGS: 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.

Full Text

Duke Authors

Cited Authors

  • Parikh, KS; Piccini, JP

Published Date

  • December 2017

Published In

Volume / Issue

  • 14 / 6

Start / End Page

  • 529 - 535

PubMed ID

  • 28975475

Pubmed Central ID

  • 28975475

Electronic International Standard Serial Number (EISSN)

  • 1546-9549

Digital Object Identifier (DOI)

  • 10.1007/s11897-017-0364-6

Language

  • eng

Conference Location

  • United States