Evidence map›Paper›PMID 39232490›Full record

SynthesisLancet (London, England)2024

Mineralocorticoid receptor antagonists in heart failure: an individual patient level meta-analysis.

Pardeep S Jhund, Atefeh Talebi, Alasdair D Henderson, Brian L Claggett, Muthiah Vaduganathan, Akshay S Desai, Carolyn S P Lam, Bertram Pitt, Michele Senni, Sanjiv J Shah and 4 more

Registry-linked trialAbstract readMeta-Analysis
PubMed Publisher
In one paragraph

Synthesis in Lancet (London, England), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04435626 (A Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled Study to Evaluate the Efficacy and Safety of Finerenone on Morbidity and Mortality in Participants With Heart Failure), which is not on this map. Cited by 87 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
87citing papers in PubMed, 4 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

NCT04435626 phase3completednot on this map

A Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled Study to Evaluate the Efficacy and Safety of Finerenone on Morbidity and Mortality in Participants With Heart Failure (NYHA II-IV) and Left Ventricular Ejection Fraction ≥ 40% (LVEF ≥ 40%)

TypeinterventionalSponsorBayerRan2020 to 2024Enrolled6,016ConditionsHeart FailureArmsFinerenone (BAY94-8862), Placebo
3 · Its place in the literature

Who cites it

87 citing papers in PubMed, 4 syntheses or guidelines pooled it.

  1. Pooled it
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  7. Update on clinical heart failure trials.Clinical research in cardiology : official journal of the German Cardiac Society · 2026
    Review
  8. Breakthrough drugs in the treatment of hypertension-related disease.Hypertension research : official journal of the Japanese Society of Hypertension · 2026
    Review
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27 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Pardeep S JhundBHF Glasgow Cardiovascular Research Centre, School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK.
Atefeh TalebiBHF Glasgow Cardiovascular Research Centre, School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK.
Alasdair D HendersonBHF Glasgow Cardiovascular Research Centre, School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK.
Brian L ClaggettCardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Muthiah VaduganathanCardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Akshay S DesaiCardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Carolyn S P LamNational Heart Centre Singapore, Singapore; Duke-National University of Singapore, Singapore.
Bertram PittUniversity of Michigan, School of Medicine, Ann Arbor, MI, USA.
Michele SenniUniversity of Milano-Bicocca, Milan, Italy; Papa Giovanni XXIII Hospital, Bergamo, Italy.
Sanjiv J ShahNorthwestern University Feinberg School of Medicine, Chicago, IL, USA.
Adriaan A VoorsUniversity of Groningen, Groningen, Netherlands.
Faiez ZannadUniversité de Lorraine, Inserm Clinical Investigation Centre, CHU, Nancy, France.
Scott D SolomonCardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
John J V McMurrayBHF Glasgow Cardiovascular Research Centre, School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK. Electronic address: john.mcmurray@glasgow.ac.uk.

Funding

HeartShare DeCODE-HF: Data translation center to Combine Omics, Deep phenotyping, and Electronic health records for Heart Failure subtypes and treatment targetsU54HL160273 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Abel N. Kho, Yuan Luo · 2021 to 2026
$19.0M
Machine learning for the automated identification and tracking of rare myocardial diseasesR01HL140731 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MACRAE, CALUM A., SHAH, SANJIV J · 2018 to 2021
$2.8M
Precision Medicine for Dilated Cardiomyopathy—Novel Assessment of Cardiac Mechanics via Speckle Tracking Echocardiography to Identify Early PhenotypesR01HL149423 · NHLBI · OHIO STATE UNIVERSITY · PI HERSHBERGER, RAY E., KINNAMON, DANIEL DAVIS · 2019 to 2022
$1.6M
NHLBI NIH HHS R01 HL140731NHLBI NIH HHS R01 HL149423NHLBI NIH HHS U54 HL160273
6 · The paper itself

Abstract

backgroundMineralocorticoid receptor antagonists (MRAs) reduce hospitalisations and death in patients with heart failure and reduced ejection fraction (HFrEF), but the benefit in patients with heart failure and mildly reduced ejection fraction (HFmrEF) or heart failure and preserved ejection fraction (HFpEF) is unclear. We evaluated the effect of MRAs in four trials that enrolled patients with heart failure across the range of ejection fraction.

methodsThis is a prespecified, individual patient level meta-analysis of the RALES (spironolactone) and EMPHASIS-HF (eplerenone) trials, which enrolled patients with HFrEF, and of the TOPCAT (spironolactone) and FINEARTS-HF (finerenone) trials, which enrolled patients with HFmrEF or HFpEF. The primary outcome of this meta-analysis was a composite of time to first hospitalisation for heart failure or cardiovascular death. We also estimated the effect of MRAs on components of this composite, total (first or repeat) heart failure hospitalisations (with and without cardiovascular deaths), and all-cause death. Safety outcomes were also assessed, including serum creatinine, estimated glomerular filtration rate, serum potassium, and systolic blood pressure. An interaction between trials and treatment was tested to examine the heterogeneity of effect in these populations. This study is registered with PROSPERO, CRD42024541487.

findings13 846 patients were included in the four trials. MRAs reduced the risk of cardiovascular death or heart failure hospitalisation (hazard ratio 0·77 [95% CI 0·72-0·83]). There was a statistically significant interaction by trials and treatment (p for interaction=0·0012) due to the greater efficacy in HFrEF (0·66 [0·59-0·73]) compared with HFmrEF or HFpEF (0·87 [0·79-0·95]). We observed significant reductions in heart failure hospitalisation in the HFrEF trials (0·63 [0·55-0·72]) and the HFmrEF or HFpEF trials (0·82 [0·74-0·91]). The same pattern was observed for total heart failure hospitalisations with or without cardiovascular death. Cardiovascular death was reduced in the HFrEF trials (0·72 [0·63-0·82]) but not in the HFmrEF or HFpEF trials (0·92 [0·80-1·05]). All-cause death was also reduced in the HFrEF trials (0·73 [0·65-0·83]) but not in the HFmrEF or HFpEF trials (0·94 [0·85-1·03]). With an MRA, the risk of hyperkalaemia was doubled compared with placebo (odds ratio 2·27 [95% CI 2·02-2·56]), but the incidence of serious hyperkalaemia (serum potassium >6·0 mmol/L) was low (2·9% vs 1·4%); the risk of hypokalaemia (potassium <3·5 mmol/L) was halved (0·51 [0·45-0·57]; 7% vs 14%).

interpretationSteroidal MRAs reduce the risk of cardiovascular death or heart failure hospitalisation in patients with HFrEF and non-steroidal MRAs reduce this risk in patients with HFmrEF or HFpEF.

fundingNone.

Indexed as

EplerenoneHeart FailureHospitalizationMineralocorticoid Receptor AntagonistsNaphthyridinesSpironolactoneStroke VolumeAgedFemaleHumansMaleMiddle AgedRandomized Controlled Trials as TopicTreatment OutcomeEplerenonefinerenoneMineralocorticoid Receptor AntagonistsNaphthyridinesSpironolactone

Identifiers

PMID39232490

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.