Erschienen in:
03.10.2017 | Genetics of Heart Failure (K Adams, Section Editor)
Pharmacogenomics of Bucindolol in Atrial Fibrillation and Heart Failure
verfasst von:
Kishan S. Parikh, Jonathan P. Piccini
Erschienen in:
Current Heart Failure Reports
|
Ausgabe 6/2017
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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.
Summary
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.