Trial reportJACC. Heart failure2013
Prevention of atrial fibrillation by bucindolol is dependent on the beta₁389 Arg/Gly adrenergic receptor polymorphism.
Trial report in JACC. Heart failure, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 26 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Beta-Blocker Evaluation in Survival Trial (BEST)
GENETIC-AF - A Genotype-Directed Comparative Effectiveness Trial of Bucindolol and Toprol-XL for Prevention of Symptomatic Atrial Fibrillation/Atrial Flutter in Patients With Heart Failure
Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Pharmacological interventions for heart failure in people with chronic kidney disease.The Cochrane database of systematic reviews · 2020Pooled it
- Bucindolol for the Maintenance of Sinus Rhythm in a Genotype-Defined HF Population: The GENETIC-AF Trial.JACC. Heart failure · 2019Trial
- Translating genome-wide association studies at multiple scales: Drug target prioritization, cellular architectures, and organ imaging.Cell genomics · 2026Review
- βmedRxiv : the preprint server for health sciences · 2025Article
- Practical compendium of antiarrhythmic drugs: a clinical consensus statement of the European Heart Rhythm Association of the European Society of Cardiology.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2025Review
- Symptoms Burden as a Clinical Outcomes Assessment in Heart Failure Patients With Atrial Fibrillation.JACC. Heart failure · 2025Article
- Impact of Genetic Variation in Adrenergic Receptors on β-Blocker Effectiveness and Safety in Cardiovascular Disease Management: A Systematic Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Genetic Variants of Adrenoceptors.Handbook of experimental pharmacology · 2024Review
- Heart failure with reduced ejection fraction and atrial fibrillation: a Sub-Saharan African perspective.ESC heart failure · 2023Review
- Dose-limiting, adverse event-associated bradycardia with β-blocker treatment of atrial fibrillation in the GENETIC-AF trial.Heart rhythm O2 · 2022Article
- Pharmacogenomics Informs Cardiovascular Pharmacotherapy.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Genetics of atrial fibrillation-practical applications for clinical management: if not now, when and how?Cardiovascular research · 2021Review
- How Will Genetics Inform the Clinical Care of Atrial Fibrillation?Circulation research · 2020Review
- Review
- Dose Response of β-Blockers in Adrenergic Receptor Polymorphism Genotypes.Circulation. Genomic and precision medicine · 2018Article
- Pharmacogenomics of Bucindolol in Atrial Fibrillation and Heart Failure.Current heart failure reports · 2017Review
- Precision Cardiovascular Medicine: State of Genetic Testing.Mayo Clinic proceedings · 2017Review
- Changes in Left Ventricular Ejection Fraction Predict Survival and Hospitalization in Heart Failure With Reduced Ejection Fraction.Circulation. Heart failure · 2016Article
- Cardiovascular Pharmacogenomics--Implications for Patients With CKD.Advances in chronic kidney disease · 2016Review
- Hypertension pharmacogenomics: in search of personalized treatment approaches.Nature reviews. Nephrology · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 7 institutions in 1 country.
Funding
Abstract
objectivesThis study assessed the impact of bucindolol, a beta-blocker/sympatholytic agent, on the development of atrial fibrillation (AF) in advanced chronic heart failure with reduced left ventricular ejection fraction (HFREF) patients enrolled in the BEST (Beta-Blocker Evaluation of Survival Trial).
backgroundβ-blockers have modest efficacy for AF prevention in HFREF patients. Bucindolol's effects on HF and ventricular arrhythmic endpoints are genetically modulated by β₁- and α(2c)-adrenergic receptor (AR) polymorphisms that can be used to subdivide HFREF populations into those with bucindolol effectiveness levels that are enhanced, unchanged, or lost.
methodsBEST enrolled 2,708 New York Heart Association (NYHA) class III to IV HFREF patients. A substudy in which 1,040 patients' DNA was genotyped for the β₁-AR position 389 Arg/Gly and the α(2c)322-325 wild type (Wt)/deletion (Del) polymorphisms, and new-onset AF was assessed from adverse event case report forms or electrocardiograms at baseline and at 3 and 12 months.
resultsIn the entire cohort, bucindolol reduced the rate of new-onset AF compared to placebo by 41% (hazard ratio [HR]: 0.59 [95% confidence interval (CI): 0.44 to 0.79], p = 0.0004). In the 493 β₁389 arginine homozygotes (Arg/Arg) in the DNA substudy, bucindolol reduced new-onset AF by 74% (HR: 0.26 [95% CI: 0.12 to 0.57]), with no effect in β₁389 Gly carriers (HR: 1.01 [95% CI: 0.56 to 1.84], interaction test = 0.008). When β₁389 Gly carriers were subdivided by α(2c) Wt homozygotes (n = 413, HR: 0.94 [95% CI: 0.48 to 1.82], p = 0.84) or Del variant carriers (n = 134, HR: 1.33 [95% CI: 0.32 to 5.64], p = 0.70), there was a positive interaction test (p = 0.016) when analyzed with β₁389 Arg homozygotes.
conclusionsBucindolol prevented new-onset AF; β₁ and α(2c) polymorphisms predicted therapeutic response; and the 47% of patients who were β₁389 Arg homozygotes had an enhanced effect size of 74%. (Beta-Blocker Evaluation in Survival Trial [BEST]; NCT00000560)
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.