---
title: "Spironolactone and early eGFR declines in HFpEF: TOPCAT Americas post-hoc analysis"
id: "pubmed-41961632"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-41961632"
content_type: "clinical_feed_article"
specialty: "Cardiology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/41961632/"
doi: "10.1093/ejhf/xuag099"
published_at: "2026-09-15T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Spironolactone and early eGFR declines in HFpEF: TOPCAT Americas post-hoc analysis
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-41961632
- **Specialty:** [Cardiology](https://medichelpline.com/clinical-feed/cardiology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/41961632/)
- **DOI:** [10.1093/ejhf/xuag099](https://doi.org/10.1093%2Fejhf%2Fxuag099)
- **Published At:** 2026-09-15T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- Study aim: to evaluate frequency, prognostic significance, and treatment implications of early acute changes in **eGFR** after initiation of a mineralocorticoid receptor antagonist (**MRA**, spironolactone) in patients with **heart failure with preserved ejection fraction (HFpEF)** enrolled in TOPCAT Americas. - Design: post-hoc analysis of 1,648 TOPCAT (Americas regional subgroup) participants; defined an early eGFR dip as a ≥15% decrease from baseline to week 4; landmark analyses examined associations with the primary composite outcome (cardiovascular death, heart failure hospitalization, or aborted cardiac arrest). - Incidence: 431 patients (26%) experienced an acute eGFR decrease within 4 weeks. The decline was more frequent with **spironolactone**: 269/817 (33%) versus placebo 162/831 (20%); odds ratio 1.97 (95% CI 1.58–2.47). - Prognosis: An early acute eGFR decrease was independently associated with a higher risk of subsequent cardiovascular outcomes regardless of randomized treatment arm. - Treatment effect: Despite the higher likelihood of an early eGFR decrease with spironolactone, spironolactone was associated with a lower risk of the primary cardiovascular outcome both in participants with an early eGFR dip [HR 0.75 (0.53–1.08)] and without [HR 0.80 (0.64–1.00)]; the interaction P = .81, indicating no evidence that the benefit differed by early eGFR change. - Magnitude analysis: Across levels of eGFR decline, the risk of the primary endpoint remained consistently lower with spironolactone than with placebo (Pinteraction = .64). - Clinical implication: Early modest **eGFR** declines after initiating an **MRA** were common and prognostically adverse but should not automatically trigger discontinuation of spironolactone, given observed treatment benefit. - Trial registration: ClinicalTrials.gov NCT00094302. - Limitations/notes: This report is a post-hoc analysis of the TOPCAT Americas subgroup; full methodological detail and additional data beyond the abstract were not provided in the source abstract.
## Clinical Analysis & Structured Key Points
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more resources ](https://pubmed.ncbi.nlm.nih.gov/41961632/#linkout) Title & authors Abstract Similar articles Publication types MeSH terms Substances Associated data Related information Grants and funding LinkOut - more resources Randomized Controlled Trial Eur J Heart Fail Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Eur+J+Heart+Fail%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Eur+J+Heart+Fail%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/41961632/) . 2026 Sep 15;28(3):538-545. doi: 10.1093/ejhf/xuag099. # Spironolactone, early acute eGFR changes, and clinical outcomes in patients with heart failure with preserved ejection fraction: insights from TOPCAT Americas [Iris E Beldhuis](https://pubmed.ncbi.nlm.nih.gov/?term=Beldhuis+IE&cauthor_id=41961632)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/41961632/#full-view-affiliation-1 "Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115, USA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/41961632/#full-view-affiliation-2 "Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands."), [Brian L Claggett](https://pubmed.ncbi.nlm.nih.gov/?term=Claggett+BL&cauthor_id=41961632)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/41961632/#full-view-affiliation-1 "Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115, USA."), [Brendon L Neuen](https://pubmed.ncbi.nlm.nih.gov/?term=Neuen+BL&cauthor_id=41961632)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/41961632/#full-view-affiliation-1 "Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115, USA.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/41961632/#full-view-affiliation-3 "Renal and Metabolic Division, The George Institute for Global Health, UNSW Sydney, Sydney, Australia."), [Safia Chatur](https://pubmed.ncbi.nlm.nih.gov/?term=Chatur+S&cauthor_id=41961632)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/41961632/#full-view-affiliation-1 "Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115, USA."), [Finnian R Mc Causland](https://pubmed.ncbi.nlm.nih.gov/?term=Mc+Causland+FR&cauthor_id=41961632)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/41961632/#full-view-affiliation-1 "Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115, USA.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/41961632/#full-view-affiliation-4 "Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA."), [Adriaan A Voors](https://pubmed.ncbi.nlm.nih.gov/?term=Voors+AA&cauthor_id=41961632)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/41961632/#full-view-affiliation-2 "Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands."), [Akshay S Desai](https://pubmed.ncbi.nlm.nih.gov/?term=Desai+AS&cauthor_id=41961632)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/41961632/#full-view-affiliation-1 "Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115, USA."), [Eldrin F Lewis](https://pubmed.ncbi.nlm.nih.gov/?term=Lewis+EF&cauthor_id=41961632)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/41961632/#full-view-affiliation-5 "Division of Cardiovascular Medicine, Stanford University School of Medicine, Palo Alto, CA, USA."), [Bertram Pitt](https://pubmed.ncbi.nlm.nih.gov/?term=Pitt+B&cauthor_id=41961632)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/41961632/#full-view-affiliation-6 "University of Michigan School of Medicine, Ann Arbor, USA."), [Marc A Pfeffer](https://pubmed.ncbi.nlm.nih.gov/?term=Pfeffer+MA&cauthor_id=41961632)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/41961632/#full-view-affiliation-1 "Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115, USA."), [Scott D Solomon](https://pubmed.ncbi.nlm.nih.gov/?term=Solomon+SD&cauthor_id=41961632)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/41961632/#full-view-affiliation-1 "Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115, USA."), [Muthiah Vaduganathan](https://pubmed.ncbi.nlm.nih.gov/?term=Vaduganathan+M&cauthor_id=41961632)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/41961632/#full-view-affiliation-1 "Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115, USA.") Affiliations Expand ### Affiliations * 1 Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115, USA. * 2 Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. * 3 Renal and Metabolic Division, The George Institute for Global Health, UNSW Sydney, Sydney, Australia. * 4 Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. * 5 Division of Cardiovascular Medicine, Stanford University School of Medicine, Palo Alto, CA, USA. * 6 University of Michigan School of Medicine, Ann Arbor, USA. * PMID: **41961632** * DOI: [ 10.1093/ejhf/xuag099 ](https://doi.org/10.1093/ejhf/xuag099) Free article Item in Clipboard Randomized Controlled Trial # Spironolactone, early acute eGFR changes, and clinical outcomes in patients with heart failure with preserved ejection fraction: insights from TOPCAT Americas Iris E Beldhuis et al. Eur J Heart Fail. 2026. Free article Show details Display options Display options Format Abstract PubMed PMID Eur J Heart Fail Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Eur+J+Heart+Fail%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Eur+J+Heart+Fail%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/41961632/) . 2026 Sep 15;28(3):538-545. doi: 10.1093/ejhf/xuag099. ### Authors [Iris E Beldhuis](https://pubmed.ncbi.nlm.nih.gov/?term=Beldhuis+IE&cauthor_id=41961632)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/41961632/#short-view-affiliation-1 "Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115, USA.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/41961632/#short-view-affiliation-2 "Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands."), [Brian L Claggett](https://pubmed.ncbi.nlm.nih.gov/?term=Claggett+BL&cauthor_id=41961632)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/41961632/#short-view-affiliation-1 "Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115, USA."), [Brendon L Neuen](https://pubmed.ncbi.nlm.nih.gov/?term=Neuen+BL&cauthor_id=41961632)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/41961632/#short-view-affiliation-1 "Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115, USA.")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/41961632/#short-view-affiliation-3 "Renal and Metabolic Division, The George Institute for Global Health, UNSW Sydney, Sydney, Australia."), [Safia Chatur](https://pubmed.ncbi.nlm.nih.gov/?term=Chatur+S&cauthor_id=41961632)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/41961632/#short-view-affiliation-1 "Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115, USA."), [Finnian R Mc Causland](https://pubmed.ncbi.nlm.nih.gov/?term=Mc+Causland+FR&cauthor_id=41961632)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/41961632/#short-view-affiliation-1 "Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115, USA.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/41961632/#short-view-affiliation-4 "Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA."), [Adriaan A Voors](https://pubmed.ncbi.nlm.nih.gov/?term=Voors+AA&cauthor_id=41961632)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/41961632/#short-view-affiliation-2 "Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands."), [Akshay S Desai](https://pubmed.ncbi.nlm.nih.gov/?term=Desai+AS&cauthor_id=41961632)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/41961632/#short-view-affiliation-1 "Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115, USA."), [Eldrin F Lewis](https://pubmed.ncbi.nlm.nih.gov/?term=Lewis+EF&cauthor_id=41961632)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/41961632/#short-view-affiliation-5 "Division of Cardiovascular Medicine, Stanford University School of Medicine, Palo Alto, CA, USA."), [Bertram Pitt](https://pubmed.ncbi.nlm.nih.gov/?term=Pitt+B&cauthor_id=41961632)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/41961632/#short-view-affiliation-6 "University of Michigan School of Medicine, Ann Arbor, USA."), [Marc A Pfeffer](https://pubmed.ncbi.nlm.nih.gov/?term=Pfeffer+MA&cauthor_id=41961632)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/41961632/#short-view-affiliation-1 "Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115, USA."), [Scott D Solomon](https://pubmed.ncbi.nlm.nih.gov/?term=Solomon+SD&cauthor_id=41961632)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/41961632/#short-view-affiliation-1 "Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115, USA."), [Muthiah Vaduganathan](https://pubmed.ncbi.nlm.nih.gov/?term=Vaduganathan+M&cauthor_id=41961632)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/41961632/#short-view-affiliation-1 "Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115, USA.") ### Affiliations * 1 Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115, USA. * 2 Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. * 3 Renal and Metabolic Division, The George Institute for Global Health, UNSW Sydney, Sydney, Australia. * 4 Renal Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. * 5 Division of Cardiovascular Medicine, Stanford University School of Medicine, Palo Alto, CA, USA. * 6 University of Michigan School of Medicine, Ann Arbor, USA. * PMID: **41961632** * DOI: [ 10.1093/ejhf/xuag099 ](https://doi.org/10.1093/ejhf/xuag099) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract **Aims:** Early acute changes in estimated glomerular filtration rate (eGFR) have been well described with renin-angiotensin system inhibitors and sodium-glucose cotransporter-2 inhibitors, but less is known about the frequency, prognostic relevance, and implications of these changes after mineralocorticoid receptor antagonist (MRA) initiation in patients with heart failure with preserved ejection fraction (HFpEF). **Methods:** We performed a post-hoc analysis of 1648 patients enrolled in the TOPCAT trial (Americas regional subgroup), defining an early eGFR dip as a ≥15% decrease in eGFR between baseline and week 4. Landmark analyses assessed the association of eGFR changes, treatment, and the primary composite endpoint (cardiovascular death, HF hospitalization, or aborted cardiac arrest). **Results:** Within 4 weeks of treatment initiation, 431 (26%) patients experienced acute eGFR decrease with a higher proportion of patients assigned to spironolactone [269 (33%)] compared with placebo [162 (20%)] (odds ratio 1.97; 95% confidence interval 1.58-2.47). An acute eGFR decrease was independently associated with higher risk of subsequent cardiovascular outcomes, irrespective of treatment arm. However, treatment with spironolactone appeared beneficial in reducing the primary cardiovascular outcome irrespective of the presence [hazard ratio 0.75 (0.53-1.08)] or absence [0.80 (0.64-1.00)] of early eGFR decrease (Pinteraction = .81). At any given magnitude of eGFR decline, risk of the primary endpoint was consistently lower with spironolactone compared with placebo (Pinteraction = .64). **Conclusions:** Early acute eGFR changes were common and adversely prognostic in patients with HFpEF. Spironolactone treatment was beneficial in improving cardiovascular outcomes, despite a modest increase in the likelihood of acute eGFR decrease. An acute eGFR decrease early after MRA initiation should not automatically prompt treatment discontinuation. **Trial registration:** ClinicalTrials.gov [NCT00094302](http://clinicaltrials.gov/show/NCT00094302 "See in ClinicalTrials.gov"). **Keywords:** Heart failure with preserved ejection fraction; Mineralocorticoid receptor antagonists; Spironolactone; eGFR dip. © The Author(s) 2026. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Similar articles * [ Prognostic Importance of Impaired Systolic Function in Heart Failure With Preserved Ejection Fraction and the Impact of Spironolactone. ](https://pubmed.ncbi.nlm.nih
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