ArticleCirculation. Heart failure2020
Polygenic Score for β-Blocker Survival Benefit in European Ancestry Patients With Reduced Ejection Fraction Heart Failure.
Article in Circulation. Heart failure, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
33 citing papers in PubMed, 2 syntheses or guidelines pooled it, 41 citations in OpenAlex.
- Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC) for CYP2D6, ADRB1, ADRB2, ADRA2C, GRK4, and GRK5 Genotypes and Beta-Blocker Therapy.Clinical pharmacology and therapeutics · 2024Guideline
- Common Variants onCirculation. Heart failure · 2023Pooled it
- Equal Treatment, Unequal Outcomes? Debunking the Racial Disparity in Renin Angiotensin Aldosterone System Inhibitor-Associated Reduction in Heart Failure Hospitalizations.Journal of cardiac failure · 2025Trial
- Pharmacogenomics polygenic risk score for drug response prediction using PRS-PGx methods.Nature communications · 2022Trial
- Polygenic risk scores in pharmacogenomics: methodological challenges, current applications, and perspectives for clinical implementation.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2026Article
- Polygenic risk scores for cardiovascular disease: clinical utility and limitations.The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology · 2026Review
- Genetic and Genomic Testing in Cardiovascular Disease: A Policy Statement From the American Heart Association.Circulation · 2025Review
- Proteomics-based clustering outperforms clinical clustering in identifying people with heart failure with distinct outcomes.Communications medicine · 2025Article
- Pathway-Specific Polygenic Scores for Predicting Clinical Lithium Treatment Response in Patients With Bipolar Disorder.Biological psychiatry global open science · 2025Article
- Review
- Review of the contribution of clinical and genetic factors to the racial disparity in taxane-induced peripheral neuropathy.Critical reviews in oncology/hematology · 2025Review
- The Beta-Blocker Pharmacogenetic Puzzle: More Pieces of Evidence for Pharmacodynamic Candidate Variants.Clinical and translational science · 2025Article
- Drug Discovery and Development for Heart Failure Using Multi-Omics Approaches.International journal of molecular sciences · 2025Review
- Polygenic modelling and machine learning approaches in pharmacogenomics: Importance in downstream analysis of genome-wide association study data.British journal of clinical pharmacology · 2025Review
- Polygenic Risk Scores in Human Disease.Clinical chemistry · 2025Review
- Characterizing the genetic architecture of drug response using gene-context interaction methods.Cell genomics · 2024Article
- Pharmacogenomics polygenic risk score: Ready or not for prime time?Clinical and translational science · 2024Review
- Using Omics to Identify Novel Therapeutic Targets in Heart Failure.Circulation. Genomic and precision medicine · 2024Review
- The polygenic implication of clopidogrel responsiveness: Insights from platelet reactivity analysis and next-generation sequencing.PloS one · 2024Article
- Applying polygenic risk score methods to pharmacogenomics GWAS: challenges and opportunities.Briefings in bioinformatics · 2023Article
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Authors and funding
15 authors at 8 institutions in 4 countries.
Funding
Abstract
backgroundβ-Blockers (BBs) are mainstay therapy for heart failure with reduced ejection fraction. However, individual patient responses to BB vary, which may be partially due to genetic variation. The goal of this study was to derive and validate the first polygenic response predictor (PRP) for BB survival benefit in heart failure with reduced ejection fraction patients.
methodsDerivation and validation analyses were performed in n=1436 total HF patients of European descent and with ejection fraction <50%. The PRP was derived in a random subset of the Henry Ford Heart Failure Pharmacogenomic Registry (n=248) and then validated in a meta-analysis of the remaining patients from Henry Ford Heart Failure Pharmacogenomic Registry (n=247), the TIME-CHF (Trial of Intensified Versus Standard Medical Therapy in Elderly Patients With Congestive Heart Failure; n=431), and HF-ACTION trial (Heart Failure: a Controlled Trial Investigating Outcomes of Exercise Training; n=510). The PRP was constructed from a genome-wide analysis of BB×genotype interaction predicting time to all-cause mortality, adjusted for Meta-Analysis Global Group in Chronic Heart Failure score, genotype, level of BB exposure, and BB propensity score.
resultsFive-fold cross-validation summaries out to 1000 single-nucleotide polymorphisms identified optimal prediction with a 44 single-nucleotide polymorphism score and cutoff at the 30th percentile. In validation testing (n=1188), greater BB exposure was associated with reduced all-cause mortality in patients with low PRP score (n=251; hazard ratio, 0.19 [95% CI, 0.04-0.51];
conclusionsAmong patients of European ancestry with heart failure with reduced ejection fraction, a PRP distinguished patients who derived substantial survival benefit from BB exposure from a larger group that did not. Additional work is needed to prospectively test clinical utility and to develop PRPs for other population groups and other medications.
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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 Socratic graph.