{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T22:06:13Z","timestamp":1784066773214,"version":"3.55.0"},"reference-count":31,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T00:00:00Z","timestamp":1635379200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Aims<\/jats:title>\n<jats:p>Impaired renal function is a major contributor to the low proportion of mineralocorticoid receptor antagonist (MRA) treatment in patients with heart failure with reduced ejection fraction (HFrEF). Our aims were to investigate the impact of MRA treatment on all-cause mortality and worsening renal function (WRF) in patients with HFrEF and moderately impaired renal function.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Retrospective data between 2010\u20132018 on HFrEF patients from a single-centre hospital with estimated glomerular renal function (eGFR) &lt; 60 ml\/min\/1.73 m<jats:sup>2<\/jats:sup> were analysed. WRF was defined as a decline of by eGFR \u2265 20%.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>416 patients were included, 131 patients on MRA and 285 without MRA, mean age was 77 years (SD \u00b1 9) and 82 years (SD \u00b1 9), respectively. Median follow-up was 2 years. 128 patients (32%) experienced WRF, 25% in the MRA group and 30% in patients without MRA (p = 0.293). In multivariable analysis, hospitalization for heart failure and systolic blood pressure were associated with WRF (p = 0.015 and p = &lt;0.001), but not use of MRA (p = 0.421). MRA treatment had no impact on the risk of adjusted all-cause mortality (HR 0.93; 95% CI, 0.66\u20131.32 p = 0.685). WRF was associated with increased adjusted risk of all-cause mortality (HR 1.43; 95% CI, 1.07\u20131.89 p = 0.014). Use of MRA did not increase the adjusted overall risk of mortality even when experiencing WRF (HR 1.15; 95% CI, 0.81\u20131.63 p = 0.422).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>In this cohort of elderly HFrEF patients with moderately impaired renal function, MRA did not increase risk for WRF or all-cause mortality.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0258949","type":"journal-article","created":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T17:31:28Z","timestamp":1635442288000},"page":"e0258949","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Mineralocorticoid receptor antagonists use in patients with heart failure and impaired renal function"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9319-0242","authenticated-orcid":true,"given":"Anna","family":"Jonsson Holmdahl","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6785-2895","authenticated-orcid":true,"given":"Helena","family":"Norberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredrik","family":"Valham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellinor","family":"Bergdahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krister","family":"Lindmark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,10,28]]},"reference":[{"issue":"4","key":"pone.0258949.ref001","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.jacc.2018.04.070","article-title":"Medical Therapy for Heart Failure With Reduced Ejection Fraction: The CHAMP-HF Registry","volume":"72","author":"SJ Greene","year":"2018","journal-title":"J Am Coll Cardiol"},{"issue":"9","key":"pone.0258949.ref002","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1002\/ejhf.1182","article-title":"Factors associated with underuse of mineralocorticoid receptor antagonists in heart failure with reduced ejection fraction: an analysis of 11 215 patients from the Swedish Heart Failure Registry","volume":"20","author":"G Savarese","year":"2018","journal-title":"Eur J Heart Fail"},{"issue":"1","key":"pone.0258949.ref003","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1002\/ejhf.13","article-title":"Worsening renal function during renin-angiotensin-aldosterone system inhibitor initiation and long-term outcomes in patients with left ventricular systolic dysfunction","volume":"16","author":"H Clark","year":"2014","journal-title":"European journal of heart failure"},{"issue":"2","key":"pone.0258949.ref004","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.ejheart.2008.01.011","article-title":"Worsening renal function in patients hospitalised for acute heart failure: clinical implications and prognostic significance","volume":"10","author":"M Metra","year":"2008","journal-title":"Eur J Heart Fail"},{"issue":"9","key":"pone.0258949.ref005","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1093\/eurjhf\/hfp108","article-title":"Both in- and out-hospital worsening of renal function predict outcome in patients with heart failure: results from the Coordinating Study Evaluating Outcome of Advising and Counseling in Heart Failure (COACH)","volume":"11","author":"K Damman","year":"2009","journal-title":"European journal of heart failure"},{"issue":"5","key":"pone.0258949.ref006","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1093\/eurheartj\/ehi696","article-title":"Incidence of renal dysfunction over 6 months in patients with chronic heart failure due to left ventricular systolic dysfunction: contributing factors and relationship to prognosis","volume":"27","author":"R de Silva","year":"2006","journal-title":"Eur Heart J"},{"issue":"10","key":"pone.0258949.ref007","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1056\/NEJM199909023411001","article-title":"The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators","volume":"341","author":"B Pitt","year":"1999","journal-title":"N Engl J Med"},{"issue":"1","key":"pone.0258949.ref008","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1056\/NEJMoa1009492","article-title":"Eplerenone in patients with systolic heart failure and mild symptoms","volume":"364","author":"F Zannad","year":"2011","journal-title":"N Engl J Med"},{"issue":"14","key":"pone.0258949.ref009","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1056\/NEJMoa030207","article-title":"Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction","volume":"348","author":"B Pitt","year":"2003","journal-title":"N Engl J Med"},{"key":"pone.0258949.ref010","article-title":"2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure","author":"TA McDonagh","year":"2021","journal-title":"Eur Heart J"},{"issue":"5","key":"pone.0258949.ref011","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1161\/CIRCHEARTFAILURE.109.912683","article-title":"Comparison of medical therapy dosing in outpatients cared for in cardiology practices with heart failure and reduced ejection fraction with and without device therapy: report from IMPROVE HF","volume":"3","author":"JT Heywood","year":"2010","journal-title":"Circulation Heart failure"},{"issue":"5","key":"pone.0258949.ref012","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1002\/ejhf.496","article-title":"Use of evidence-based therapy and survival in heart failure in Sweden 2003\u20132012.","volume":"18","author":"T Thorvaldsen","year":"2016","journal-title":"European journal of heart failure"},{"issue":"7","key":"pone.0258949.ref013","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1093\/eurjhf\/hft050","article-title":"EURObservational Research Programme: regional differences and 1-year follow-up results of the Heart Failure Pilot Survey (ESC-HF Pilot)","volume":"15","author":"AP Maggioni","year":"2013","journal-title":"Eur J Heart Fail"},{"issue":"5","key":"pone.0258949.ref014","doi-asserted-by":"crossref","first-page":"e12459","DOI":"10.1111\/1755-5922.12459","article-title":"Obstacles to mineralocorticoid receptor antagonists in a community-based heart failure population","volume":"36","author":"A Jonsson","year":"2018","journal-title":"Cardiovasc Ther"},{"issue":"3","key":"pone.0258949.ref015","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1161\/CIRCOUTCOMES.109.879478","article-title":"Treatment and risk in heart failure: gaps in evidence or quality?","volume":"3","author":"PN Peterson","year":"2010","journal-title":"Circ Cardiovasc Qual Outcomes"},{"issue":"6","key":"pone.0258949.ref016","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1111\/j.1523-1755.2005.00365.x","article-title":"Definition and classification of chronic kidney disease: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO)","volume":"67","author":"AS Levey","year":"2005","journal-title":"Kidney Int"},{"issue":"3","key":"pone.0258949.ref017","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1002\/ehf2.12643","article-title":"Comparison of creatinine-based methods for estimating glomerular filtration rate in patients with heart failure","volume":"7","author":"A Jonsson","year":"2020","journal-title":"ESC Heart Fail"},{"issue":"7","key":"pone.0258949.ref018","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1093\/eurheartj\/eht386","article-title":"Renal impairment, worsening renal function, and outcome in patients with heart failure: an updated meta-analysis","volume":"35","author":"K Damman","year":"2014","journal-title":"Eur Heart J"},{"issue":"20","key":"pone.0258949.ref019","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1016\/j.jacc.2012.07.048","article-title":"Influence of baseline and worsening renal function on efficacy of spironolactone in patients With severe heart failure: insights from RALES (Randomized Aldactone Evaluation Study)","volume":"60","author":"O Vardeny","year":"2012","journal-title":"Journal of the American College of Cardiology"},{"issue":"2","key":"pone.0258949.ref020","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1161\/CIRCULATIONAHA.111.028282","article-title":"Determinants and consequences of renal function variations with aldosterone blocker therapy in heart failure patients after myocardial infarction: insights from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study","volume":"125","author":"P Rossignol","year":"2012","journal-title":"Circulation"},{"issue":"1","key":"pone.0258949.ref021","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1161\/CIRCHEARTFAILURE.113.000792","article-title":"Incidence, determinants, and prognostic significance of hyperkalemia and worsening renal function in patients with heart failure receiving the mineralocorticoid receptor antagonist eplerenone or placebo in addition to optimal medical therapy: results from the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF)","volume":"7","author":"P Rossignol","year":"2014","journal-title":"Circ Heart Fail"},{"issue":"1","key":"pone.0258949.ref022","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.jacc.2003.07.031","article-title":"Incidence, predictors at admission, and impact of worsening renal function among patients hospitalized with heart failure","volume":"43","author":"DE Forman","year":"2004","journal-title":"Journal of the American College of Cardiology"},{"issue":"9","key":"pone.0258949.ref023","first-page":"1110","article-title":"Correlates and impact on outcomes of worsening renal function in patients > or = 65 years of age with heart failure","volume":"85","author":"HM Krumholz","year":"2000","journal-title":"Am J Cardiol"},{"issue":"2","key":"pone.0258949.ref024","doi-asserted-by":"crossref","first-page":"e000568","DOI":"10.1136\/openhrt-2016-000568","article-title":"Comparison of the Chronic Kidney Disease Epidemiology Collaboration, the Modification of Diet in Renal Disease study and the Cockcroft-Gault equation in patients with heart failure","volume":"4","author":"K Szummer","year":"2017","journal-title":"Open Heart"},{"issue":"2","key":"pone.0258949.ref025","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.pcad.2011.01.003","article-title":"The cardiorenal syndrome in heart failure","volume":"54","author":"K Damman","year":"2011","journal-title":"Prog Cardiovasc Dis"},{"issue":"19","key":"pone.0258949.ref026","doi-asserted-by":"crossref","first-page":"2512","DOI":"10.1161\/01.CIR.0000071081.35693.9A","article-title":"Eplerenone: cardiovascular protection","volume":"107","author":"NJ Brown","year":"2003","journal-title":"Circulation"},{"issue":"1","key":"pone.0258949.ref027","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1523-1755.2004.00701.x","article-title":"Aldosterone in the development and progression of renal injury","volume":"66","author":"NK Hollenberg","year":"2004","journal-title":"Kidney Int"},{"issue":"46","key":"pone.0258949.ref028","doi-asserted-by":"crossref","first-page":"5528","DOI":"10.2174\/1381612825666190306162658","article-title":"Mineralocorticoid Receptor Antagonists for Nephroprotection: Current Evidence and Future Perspectives","volume":"24","author":"PA Sarafidis","year":"2018","journal-title":"Curr Pharm Des"},{"issue":"1","key":"pone.0258949.ref029","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1053\/j.ajkd.2005.03.007","article-title":"Antagonists of aldosterone and proteinuria in patients with CKD: an uncontrolled pilot study","volume":"46","author":"S Bianchi","year":"2005","journal-title":"American journal of kidney diseases: the official journal of the National Kidney Foundation"},{"issue":"6","key":"pone.0258949.ref030","doi-asserted-by":"crossref","first-page":"2829","DOI":"10.1111\/j.1523-1755.2005.00756.x","article-title":"Beneficial impact of spironolactone in diabetic nephropathy","volume":"68","author":"KJ Schjoedt","year":"2005","journal-title":"Kidney Int"},{"issue":"27","key":"pone.0258949.ref031","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1093\/eurheartj\/ehw128","article-title":"2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failureThe Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC","volume":"37","author":"P Ponikowski","year":"2016","journal-title":"European Heart Journal"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0258949","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T17:31:50Z","timestamp":1635442310000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0258949"}},"subtitle":[],"editor":[{"given":"Alberto","family":"Aimo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,10,28]]},"references-count":31,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,10,28]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0258949","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,28]]}}}