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Pharmacogenomics of Bucindolol in Atrial Fibrillation and Heart Failure. 2017

Kishan S Parikh, and Jonathan P Piccini
Duke Clinical Research Institute, Durham, NC, USA. kishan.parikh@duke.edu.

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.

UI MeSH Term Description Entries
D010597 Pharmacogenetics A branch of genetics which deals with the genetic variability in individual responses to drugs and drug metabolism (BIOTRANSFORMATION). Pharmacogenomics
D011412 Propanolamines AMINO ALCOHOLS containing the propanolamine (NH2CH2CHOHCH2) group and its derivatives. Aminopropanols
D005838 Genotype The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS. Genogroup,Genogroups,Genotypes
D006333 Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION. Cardiac Failure,Heart Decompensation,Congestive Heart Failure,Heart Failure, Congestive,Heart Failure, Left-Sided,Heart Failure, Right-Sided,Left-Sided Heart Failure,Myocardial Failure,Right-Sided Heart Failure,Decompensation, Heart,Heart Failure, Left Sided,Heart Failure, Right Sided,Left Sided Heart Failure,Right Sided Heart Failure
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000319 Adrenergic beta-Antagonists Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. Adrenergic beta-Antagonist,Adrenergic beta-Receptor Blockader,Adrenergic beta-Receptor Blockaders,beta-Adrenergic Antagonist,beta-Adrenergic Blocker,beta-Adrenergic Blocking Agent,beta-Adrenergic Blocking Agents,beta-Adrenergic Receptor Blockader,beta-Adrenergic Receptor Blockaders,beta-Adrenoceptor Antagonist,beta-Blockers, Adrenergic,beta-Adrenergic Antagonists,beta-Adrenergic Blockers,beta-Adrenoceptor Antagonists,Adrenergic beta Antagonist,Adrenergic beta Antagonists,Adrenergic beta Receptor Blockader,Adrenergic beta Receptor Blockaders,Adrenergic beta-Blockers,Agent, beta-Adrenergic Blocking,Agents, beta-Adrenergic Blocking,Antagonist, beta-Adrenergic,Antagonist, beta-Adrenoceptor,Antagonists, beta-Adrenergic,Antagonists, beta-Adrenoceptor,Blockader, Adrenergic beta-Receptor,Blockader, beta-Adrenergic Receptor,Blockaders, Adrenergic beta-Receptor,Blockaders, beta-Adrenergic Receptor,Blocker, beta-Adrenergic,Blockers, beta-Adrenergic,Blocking Agent, beta-Adrenergic,Blocking Agents, beta-Adrenergic,Receptor Blockader, beta-Adrenergic,Receptor Blockaders, beta-Adrenergic,beta Adrenergic Antagonist,beta Adrenergic Antagonists,beta Adrenergic Blocker,beta Adrenergic Blockers,beta Adrenergic Blocking Agent,beta Adrenergic Blocking Agents,beta Adrenergic Receptor Blockader,beta Adrenergic Receptor Blockaders,beta Adrenoceptor Antagonist,beta Adrenoceptor Antagonists,beta Blockers, Adrenergic,beta-Antagonist, Adrenergic,beta-Antagonists, Adrenergic,beta-Receptor Blockader, Adrenergic,beta-Receptor Blockaders, Adrenergic
D001281 Atrial Fibrillation Abnormal cardiac rhythm that is characterized by rapid, uncoordinated firing of electrical impulses in the upper chambers of the heart (HEART ATRIA). In such case, blood cannot be effectively pumped into the lower chambers of the heart (HEART VENTRICLES). It is caused by abnormal impulse generation. Auricular Fibrillation,Familial Atrial Fibrillation,Paroxysmal Atrial Fibrillation,Persistent Atrial Fibrillation,Atrial Fibrillation, Familial,Atrial Fibrillation, Paroxysmal,Atrial Fibrillation, Persistent,Atrial Fibrillations,Atrial Fibrillations, Familial,Atrial Fibrillations, Paroxysmal,Atrial Fibrillations, Persistent,Auricular Fibrillations,Familial Atrial Fibrillations,Fibrillation, Atrial,Fibrillation, Auricular,Fibrillation, Familial Atrial,Fibrillation, Paroxysmal Atrial,Fibrillation, Persistent Atrial,Fibrillations, Atrial,Fibrillations, Auricular,Fibrillations, Familial Atrial,Fibrillations, Paroxysmal Atrial,Fibrillations, Persistent Atrial,Paroxysmal Atrial Fibrillations,Persistent Atrial Fibrillations
D013318 Stroke Volume The amount of BLOOD pumped out of the HEART per beat, not to be confused with cardiac output (volume/time). It is calculated as the difference between the end-diastolic volume and the end-systolic volume. Ventricular Ejection Fraction,Ventricular End-Diastolic Volume,Ventricular End-Systolic Volume,Ejection Fraction, Ventricular,Ejection Fractions, Ventricular,End-Diastolic Volume, Ventricular,End-Diastolic Volumes, Ventricular,End-Systolic Volume, Ventricular,End-Systolic Volumes, Ventricular,Fraction, Ventricular Ejection,Fractions, Ventricular Ejection,Stroke Volumes,Ventricular Ejection Fractions,Ventricular End Diastolic Volume,Ventricular End Systolic Volume,Ventricular End-Diastolic Volumes,Ventricular End-Systolic Volumes,Volume, Stroke,Volume, Ventricular End-Diastolic,Volume, Ventricular End-Systolic,Volumes, Stroke,Volumes, Ventricular End-Diastolic,Volumes, Ventricular End-Systolic
D018342 Receptors, Adrenergic, beta-1 A subclass of beta-adrenergic receptors (RECEPTORS, ADRENERGIC, BETA). The adrenergic beta-1 receptors are equally sensitive to EPINEPHRINE and NOREPINEPHRINE and bind the agonist DOBUTAMINE and the antagonist METOPROLOL with high affinity. They are found in the HEART, juxtaglomerular cells, and in the central and peripheral nervous systems. Adrenergic beta-1 Receptor,Adrenergic beta-1 Receptors,Receptors, beta-1 Adrenergic,beta-1 Adrenergic Receptors,Adrenergic Receptor, beta-1,Receptor, Adrenergic, beta-1,beta 1 Adrenergic Receptor,Adrenergic Receptor, beta 1,Adrenergic Receptors, beta-1,Adrenergic beta 1 Receptor,Adrenergic beta 1 Receptors,Receptor, Adrenergic beta-1,Receptor, beta-1 Adrenergic,Receptors, Adrenergic beta-1,Receptors, beta 1 Adrenergic,beta 1 Adrenergic Receptors,beta-1 Adrenergic Receptor,beta-1 Receptor, Adrenergic,beta-1 Receptors, Adrenergic

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