{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:08:38Z","timestamp":1792177718230,"version":"4.4.0"},"reference-count":12,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":561,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2024,5,23]],"date-time":"2024-05-23T00:00:00Z","timestamp":1716422400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Many patients with heart failure (HF) have chronic kidney disease (CKD) and may not tolerate mineralocorticoid receptor antagonists. We investigated the efficacy and safety of the novel mineralocorticoid receptor modulator balcinrenone in combination with dapagliflozin in a phase 2b study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>From January 2021 to October 2023, we randomized 133 adults with symptomatic HF, ejection fraction &amp;lt;60%, estimated glomerular filtration rate (eGFR)\u2009\u226530 to \u226460\u2009ml\/min\/1.73 m2 and urinary albumin-to-creatinine ratio (UACR) \u226530 to &amp;lt;3000\u2009mg\/g, to receive balcinrenone 15, 50 or 150\u2009mg\/day plus dapagliflozin 10\u2009mg\/day, or dapagliflozin 10\u2009mg\/day plus placebo, for 12\u2009weeks. Enrolment was stopped early because of slow recruitment. Relative reductions in UACR from baseline to week 12 (primary endpoint) were not significantly different between the balcinrenone plus dapagliflozin groups versus dapagliflozin plus placebo. There was no clear balcinrenone dose\u2013response relationship. There were possible dose-dependent increases in serum potassium levels, reduced eGFR in the highest dose group, and non-significant trends towards reduced N-terminal pro-B-type natriuretic peptide levels. Hyperkalaemia adverse events led to discontinuation in two participants receiving balcinrenone plus dapagliflozin and none in those receiving dapagliflozin plus placebo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>While the smaller than planned sample size limits interpretation, we did not see significant reduction in UACR in patients treated with balcinrenone plus dapagliflozin compared with dapagliflozin plus placebo.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.3294","type":"journal-article","created":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T02:35:40Z","timestamp":1716518140000},"page":"1727-1735","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Balcinrenone Plus Dapagliflozin in Patients with Heart Failure and Chronic Kidney Disease: Results from the Phase 2b MIRACLE Trial"],"prefix":"10.1093","volume":"26","author":[{"given":"Carolyn S.P.","family":"Lam","sequence":"first","affiliation":[{"name":"National Heart Centre, Singapore & Duke-National University of Singapore , Singapore ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"K\u00f8ber","sequence":"additional","affiliation":[{"name":"Rigshospitalet, Heart Centre , Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichiro","family":"Kuwahara","sequence":"additional","affiliation":[{"name":"Shinshu University School of Medicine, Department of Cardiovascular Medicine , Matsumoto ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars H.","family":"Lund","sequence":"additional","affiliation":[{"name":"Karolinska University Hospital, Stockholm, Sweden; and Division of Cardiology, Department of Medicine, Karolinska Institutet , Stockholm ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick B.","family":"Mark","sequence":"additional","affiliation":[{"name":"School of Cardiovascular and Metabolic Health, University of Glasgow , Glasgow ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda G.","family":"Mellbin","sequence":"additional","affiliation":[{"name":"Karolinska University Hospital, Stockholm, Sweden; and Division of Cardiology, Department of Medicine, Karolinska Institutet , Stockholm ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten","family":"Schou","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Herlev Hospital , Herlev ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Ely Pizzato","sequence":"additional","affiliation":[{"name":"Early Clinical Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca , Gaithersburg, MD ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Gabrielsen","sequence":"additional","affiliation":[{"name":"Early Clinical Development, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D AstraZeneca , Gothenburg ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samvel B.","family":"Gasparyan","sequence":"additional","affiliation":[{"name":"Biometrics, Late Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D AstraZeneca , Gothenburg ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Ghiretti","sequence":"additional","affiliation":[{"name":"Biometrics, Late Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D AstraZeneca , Gothenburg ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Hartleib-Geschwindner","sequence":"additional","affiliation":[{"name":"Late-stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D AstraZeneca , Gothenburg ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greggory J.","family":"Housler","sequence":"additional","affiliation":[{"name":"Early Clinical Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca , Gaithersburg, MD ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Fanti","sequence":"additional","affiliation":[{"name":"Clinical Development, Late Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca , Gaithersburg, MD ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Leonsson-Zachrisson","sequence":"additional","affiliation":[{"name":"Late-stage Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D AstraZeneca , Gothenburg ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.V.","family":"McMurray","sequence":"additional","affiliation":[{"name":"School of Cardiovascular and Metabolic Health, University of Glasgow , Glasgow ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott D.","family":"Solomon","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA, USA; Division of Cardiovascular Medicine, Brigham and Women's Hospital , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the MIRACLE Study Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,5,23]]},"reference":[{"key":"2026010913060231600_ejhf3294-bib-0001","doi-asserted-by":"crossref","first-page":"2281","DOI":"10.1016\/j.jacc.2014.08.036","article-title":"Noncardiac comorbidities in heart failure with reduced versus preserved ejection fraction","volume":"64","author":"Mentz","year":"2014","journal-title":"J Am Coll Cardiol"},{"key":"2026010913060231600_ejhf3294-bib-0002","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":"Greene","year":"2018","journal-title":"J Am Coll Cardiol"},{"key":"2026010913060231600_ejhf3294-bib-0003","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1002\/ejhf.2333","article-title":"2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). With the special contribution of the Heart Failure Association (HFA) of the ESC","volume":"24","author":"McDonagh","year":"2022","journal-title":"Eur J Heart Fail"},{"key":"2026010913060231600_ejhf3294-bib-0004","first-page":"e895","article-title":"2022 AHA\/ACC\/HFSA Guideline for the management of heart failure: A report of the American College of Cardiology\/American Heart Association Joint Committee on Clinical Practice Guidelines","volume":"145","author":"Heidenreich","year":"2022","journal-title":"Circulation"},{"key":"2026010913060231600_ejhf3294-bib-0005","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0193380","article-title":"Preclinical pharmacology of AZD9977: A novel mineralocorticoid receptor modulator separating organ protection from effects on electrolyte excretion","volume":"13","author":"Bamberg","year":"2018","journal-title":"PLoS One"},{"key":"2026010913060231600_ejhf3294-bib-0006","doi-asserted-by":"crossref","first-page":"604","DOI":"10.7326\/0003-4819-150-9-200905050-00006","article-title":"A new equation to estimate glomerular filtration rate","volume":"150","author":"Levey","year":"2009","journal-title":"Ann Intern Med"},{"key":"2026010913060231600_ejhf3294-bib-0007","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.7326\/M23-1023","article-title":"Impact of finerenone-induced albuminuria reduction on chronic kidney disease outcomes in type 2 diabetes: A mediation analysis","volume":"176","author":"Agarwal","year":"2023","journal-title":"Ann Intern Med"},{"key":"2026010913060231600_ejhf3294-bib-0008","article-title":"Aldosterone antagonists in addition to renin angiotensin system antagonists for preventing the progression of chronic kidney disease","volume":"10","author":"Chung","year":"2020","journal-title":"Cochrane Database Syst Rev"},{"key":"2026010913060231600_ejhf3294-bib-0009","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1161\/CIRCULATIONAHA.119.042929","article-title":"Dapagliflozin effects on biomarkers, symptoms, and functional status in patients with heart failure with reduced ejection fraction: The DEFINE-HF trial","volume":"140","author":"Nassif","year":"2019","journal-title":"Circulation"},{"key":"2026010913060231600_ejhf3294-bib-0010","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/S2213-8587(19)30086-5","article-title":"Albuminuria-lowering effect of dapagliflozin alone and in combination with saxagliptin and effect of dapagliflozin and saxagliptin on glycaemic control in patients with type 2 diabetes and chronic kidney disease (DELIGHT): A randomised, double-blind, placebo-controlled trial","volume":"7","author":"Pollock","year":"2019","journal-title":"Lancet Diabetes Endocrinol"},{"key":"2026010913060231600_ejhf3294-bib-0011","doi-asserted-by":"crossref","DOI":"10.1161\/CIRCHEARTFAILURE.118.005288","article-title":"Prognostic value of albuminuria and influence of spironolactone in heart failure with preserved ejection fraction","volume":"11","author":"Selvaraj","year":"2018","journal-title":"Circ Heart Fail"},{"key":"2026010913060231600_ejhf3294-bib-0012","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1001\/jama.2023.17002","article-title":"Estimated glomerular filtration rate, albuminuria, and adverse outcomes: An individual-participant data meta-analysis","volume":"330","author":"Writing Group for the CKD Prognosis Consortium","year":"2023","journal-title":"JAMA"}],"container-title":["European Journal of Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/26\/8\/1727\/65511908\/eurjhf_26_8_1727.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/26\/8\/1727\/65511908\/eurjhf_26_8_1727.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T18:07:14Z","timestamp":1767982034000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eurjhf\/article\/26\/8\/1727\/8328729"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,23]]},"references-count":12,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,5,23]]},"published-print":{"date-parts":[[2024,8,1]]}},"URL":"https:\/\/doi.org\/10.1002\/ejhf.3294","relation":{},"ISSN":["1388-9842","1879-0844"],"issn-type":[{"value":"1388-9842","type":"print"},{"value":"1879-0844","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,8]]},"published":{"date-parts":[[2024,5,23]]},"assertion":[{"value":"2024-04-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}