Evidence map›Paper›PMID 11094035›Full record

Trial reportCirculation2000

Limitation of excessive extracellular matrix turnover may contribute to survival benefit of spironolactone therapy in patients with congestive heart failure: insights from the randomized aldactone evaluation study (RALES). Rales Investigators.

F Zannad, F Alla, B Dousset, A Perez, B Pitt

Erratum issued 6 registry-linked trialsOpen access · bronzeAbstract readClinical TrialRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in Circulation, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 6 registered trials, which are not on this map. Cited by 254 papers, 11 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
254citing papers in PubMed, 11 pooled it
22.2field-weighted citation impact, top 1% of its field
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.

NCT00795912 phase4completedstarted 2003, after this paper: background citation

A Study Of The Usage Of Statins In A Community Heart Failure Population: The Impact of HMG Co-Enzyme A Reductase Inhibitors on Heart Structural Parameters, Brain Naturetic Peptide, Markers of Inflammation and Fibrosis

Ran2003Enrolled56Registered outcomes2Posted comparisons0ConditionsHeart FailureArmsAtorvastatin
PMID 11555537PMID 15302013PMID 12020481PMID 11996626PMID 11036910PMID 15926863PMID 15313958PMID 14726474PMID 12034159PMID 12009719PMID 11806812PMID 9922372other papers from this trial
Open the trial in the graph
NCT00123955 phase3completednot on this mapstarted 2005, after this paper: background citation

Exercise Intolerance in Elderly Diastolic Heart Failure

TypeinterventionalSponsorWake Forest UniversityRan2005 to 2012Enrolled80ConditionsDiastolic Heart Failure, Heart Failure, CongestiveArmsSpironolactone, Placebo
NCT00879060 phase4completednot on this mapstarted 2007, after this paper: background citation

Clinical and Therapeutic Implications of Fibrosis in Hypertrophic Cardiomyopathy

TypeinterventionalSponsorTufts Medical CenterRan2007 to 2012Enrolled53ConditionsMyocardial Fibrosis, Hypertrophic CardiomyopathyArmsSpironolactone, Placebo
NCT01708798 phase2 / phase3terminatednot on this mapstarted 2014, after this paper: background citation

A Prospective Randomized Placebo-controlled Study of the Effect of Eplerenone on Left Ventricular Diastolic Function in Women Receiving Anthracycline Therapy for Breast Cancer

TypeinterventionalSponsorUniversity of British ColumbiaRan2014 to 2016Enrolled44ConditionsBreast CancerArmsEplerenone, Placebo
NCT02502981 phase4unknown statusnot on this mapstarted 2014, after this paper: background citation

A Randomised Open Label, Blinded End Point Trial to Compare the Effects of Spironolactone With Chlortalidone on LV Mass in Stage 3 Chronic Kidney Disease (SPIRO-CKD)

TypeinterventionalSponsorUniversity Hospital BirminghamRan2014 to 2018Enrolled154ConditionsRenal Insufficiency, Chronic, Cardio-Renal SyndromeArmsSpironolactone, Chlortalidone
NCT03835676 phase4unknown statusnot on this mapstarted 2019, after this paper: background citation

Effects of Treprostinil on Right Ventricular Structure and Function in Patients With Pulmonary Arterial Hypertension

TypeinterventionalSponsorMagdi H. YacoubRan2019 to 2025Enrolled30ConditionsPulmonary HypertensionArmsTreprostinil
3 · Its place in the literature

Who cites it

254 citing papers in PubMed, 11 syntheses or guidelines pooled it, 938 citations in OpenAlex.

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194 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

F ZannadCentre d'Investigation Clinique INSERM-CHU, Laboratory of Biochemistry, Centre Hospitalier Universitaire, University Henri Poincaré, Nancy, France. cic@chu-nancy.fr
F Alla
B Dousset
A Perez
B Pitt
Monsanto (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIn congestive heart failure (CHF), extracellular matrix turnover is a major determinant of cardiac remodeling. It has been suggested that spironolactone may decrease cardiac fibrosis. We investigated the interactions between serum markers of cardiac fibrosis and the effect of spironolactone on outcome in patients with CHF. METHODS AND

resultsA sample of 261 patients from the Randomized Aldactone Evaluation Study (RALES) were randomized to placebo or spironolactone (12.5 to 50 mg daily). Serum procollagen type I carboxy-terminal peptide, procollagen type I amino-terminal peptide, and procollagen type III amino-terminal peptide (PIIINP) were assessed at baseline and at 6 months. Baseline PIIINP >3.85 microgram/L was associated with an increased risk of death (relative risk [RR] 2.36, 95% CI 1.34 to 4.18) and of death+hospitalization (RR 1.83, 95% CI 1.18 to 2.83). At 6 months, markers decreased in the spironolactone group but remained unchanged in the placebo group. The spironolactone effect on outcome was significant only in patients with above-median baseline levels of markers. RR (95% CI) values for death among patients receiving spironolactone were 0.44 (0.26 to 0.75) and 1.11 (0.66 to 1.88) in subgroups of PIIINP levels above and below the median, respectively. Similarly, RR (95% CI) values for death+hospitalization among patients receiving spironolactone were 0.45 (0.29 to 0.71) and 0.85 (0.55 to 1.33), respectively.

conclusionsIn patients with CHF, high baseline serum levels of markers of cardiac fibrosis synthesis are significantly associated with poor outcome and decrease during spironolactone therapy. The benefit from spironolactone was associated with higher levels of collagen synthesis markers. These results suggest that limitation of the excessive extracellular matrix turnover may be one of the various extrarenal mechanisms contributing to the beneficial effect of spironolactone in patients with CHF.

Indexed as

AgedAged, 80 and overExtracellular MatrixFemaleHeart FailureHumansMaleMatrix Metalloproteinase 1Middle AgedMineralocorticoid Receptor AntagonistsProcollagenSpironolactoneSurvival AnalysisSurvival RateTime FactorsTissue Inhibitor of Metalloproteinase-1Matrix Metalloproteinase 1Mineralocorticoid Receptor AntagonistsProcollagenSpironolactoneTissue Inhibitor of Metalloproteinase-1

Identifiers

PMID11094035
OpenAlexW2106493153

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.