Trial reportPharmacotherapy2021
NR3C2 genotype is associated with response to spironolactone in diastolic heart failure patients from the Aldo-DHF trial.
Trial report in Pharmacotherapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 2 of them syntheses 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Mineralocorticoid receptor antagonists for acute myocardial infarction: a systematic review and meta-analysis of randomised controlled trials.Open heart · 2025Pooled it
- Renal effects and safety between Asian and non-Asian chronic kidney disease and type 2 diabetes treated with nonsteroidal mineralocorticoid antagonists.Journal of diabetes · 2024Pooled it
- An integrated Biobank in the Swedish Heart Failure Registry-clinomics, proteomics, transcriptomics and genomics.ESC heart failure · 2026Observational
- Review
- Investigating the Role of Gene Polymorphisms in Hypertension: Evidence from the Jordanian Population.Vascular health and risk management · 2025Article
- Genetic Variation inJournal of personalized medicine · 2024Article
- Beyond Natriuretic Peptides: Unveiling the Power of Emerging Biomarkers in Heart Failure.Biomolecules · 2024Review
- Functional mutation, splice, distribution, and divergence analysis of impactful genes associated with heart failure and other cardiovascular diseases.Scientific reports · 2023Article
- Precision Medicine and the future of Cardiovascular Diseases: A Clinically Oriented Comprehensive Review.Journal of clinical medicine · 2023Review
- Pharmacogenomics of Hypertension in Africa: Paving the Way for a Pharmacogenetic-Based Approach for the Treatment of Hypertension in Africans.International journal of hypertension · 2023Review
- Pathophysiological Rationale and Clinical Evidence for Neurohormonal Modulation in Heart Failure with Preserved Ejection Fraction.Cardiac failure review · 2023Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
STUDY
objectiveThis study aimed to determine if variants in NR3C2, which codes the target protein of spironolactone, or CYP11B2, which is involved in aldosterone synthesis, were associated with spironolactone response, focused on the primary end point of diastolic function (E/e'), in Aldosterone Receptor Blockade in Diastolic Heart Failure (Aldo-DHF) participants.
designPost-hoc genetic analysis. DATA SOURCE: Data and samples were derived from the multi-center, randomized, double-blind, placebo-controlled Aldo-DHF trial. PATIENTS: Aldo-DHF participants treated with spironolactone (n = 184) or placebo (n = 178) were included.
interventionParticipants were genotyped for NR3C2 rs5522, NR3C2 rs2070951 and CYP11B2 rs1799998 via pyrosequencing. MEASUREMENTS: In the placebo and spironolactone arms, separate multivariable linear regression analyses were performed for change in E/e' with each single nucleotide polymorphism (SNP), adjusted for age, sex, and baseline E/e'. To discern potential mechanisms of a genotype effect, associated SNPs were further examined for their association with change in blood pressure, circulating procollagen type III N-terminal peptide (PIIINP), and left atrial area. MAIN
resultsCarriers of the rs5522 G allele in the placebo arm had a greater increase in E/e' over the 12-month course of the trial compared to noncarriers (β = 1.10; 95% confidence interval [CI]: 0.05-2.16; p = 0.04). No corresponding E/e' worsening by rs5522 genotype was observed in the spironolactone arm. None of the other genotypes were associated with change in E/e'. Compared to noncarriers, rs5522 G carriers also had a greater increase in left atrial area with placebo (β = 0.83; 95% CI: 0.17-1.48; p = 0.01) and a greater reduction in diastolic blood pressure with spironolactone (β = -3.56; 95% CI: -6.73 to -0.39; p = 0.03). Serum PIIINP levels were similar across rs5522 genotypes.
conclusionsOur results suggest that spironolactone attenuates progression of diastolic dysfunction associated with the NR3C2 rs5522 G allele. Validation of our findings is needed.
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