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Review
. 2017 Dec;14(6):529-535.
doi: 10.1007/s11897-017-0364-6.

Pharmacogenomics of Bucindolol in Atrial Fibrillation and Heart Failure

Kishan S Parikh  1   2 , Jonathan P Piccini  3
Affiliations
Review

Pharmacogenomics of Bucindolol in Atrial Fibrillation and Heart Failure

Kishan S Parikh et al. Curr Heart Fail Rep. 2017 Dec.

Abstract

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.

Keywords: Atrial fibrillation; Bucindolol; Heart failure; Pharmacogenomics.

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