{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:22:21Z","timestamp":1791228141495,"version":"4.1.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2013,9,1]],"date-time":"2013-09-01T00:00:00Z","timestamp":1377993600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Spironolactone treatment in humans is associated with an increased risk of hyperkalemia and renal dysfunction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Hypothesis<\/jats:title>\n                    <jats:p>Dogs with cardiac disease treated with spironolactone, in addition to conventional therapy, are not at higher risk for adverse events (AEs) than those receiving solely conventional therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Animals<\/jats:title>\n                    <jats:p>One hundred and ninety-six client-owned dogs with naturally occurring myxomatous mitral valve disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Prospective, double-blinded field study with dogs randomized to receive either spironolactone (2 mg\/kg once a day) or placebo in addition to conventional therapy (angiotensin-converting enzyme inhibitor, plus furosemide and digoxin if needed). Safety was compared between treatment groups, using the frequency of AEs, death caused by cardiac disease, renal disease, or both, and variations in serum sodium, potassium, urea, and creatinine concentrations. For the latter, population-specific reference intervals were established and out of range values (ORV) analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The number of AEs was similar in the spironolactone and reference groups (188 and 208, respectively), when followed for median duration of 217 days (range [2\u20131,333]). At each study time point, the percentage of dogs showing ORV was similar between groups. There were a higher number of deaths because of cardiac disease, renal disease or both in the reference group (30.7% versus 13.7%) (P = .0043).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Clinical Importance<\/jats:title>\n                    <jats:p>Dogs with heart failure receiving spironolactone in addition to conventional treatment are not at a higher risk for AEs, death caused by cardiac disease, renal disease, or both, hyperkalemia, or azotemia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jvim.12141","type":"journal-article","created":{"date-parts":[[2013,7,19]],"date-time":"2013-07-19T13:36:53Z","timestamp":1374241013000},"page":"1083-1091","source":"Crossref","is-referenced-by-count":19,"title":["Safety of Spironolactone in Dogs with Chronic Heart Failure because of Degenerative Valvular Disease: A Population-Based, Longitudinal Study"],"prefix":"10.1093","volume":"27","author":[{"given":"H.P.","family":"Lefebvre","sequence":"first","affiliation":[{"name":"INP, Ecole Nationale V\u00e9t\u00e9rinaire de Toulouse, Unit\u00e9 de Recherche Clinique & D\u00e9partement des Sciences Cliniques, Universit\u00e9 de Toulouse , Toulouse,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Ollivier","sequence":"additional","affiliation":[{"name":"CEVA Sant\u00e9 Animale , Libourne,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.E.","family":"Atkins","sequence":"additional","affiliation":[{"name":"North Carolina State University Department of Clinical Sciences, , Raleigh, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Combes","sequence":"additional","affiliation":[{"name":"Stalphamis , Lalande de Pomerol,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Concordet","sequence":"additional","affiliation":[{"name":"INRA, UMR 1331, Toxalim , Toulouse,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Kaltsatos","sequence":"additional","affiliation":[{"name":"CEVA Sant\u00e9 Animale , Libourne,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Baduel","sequence":"additional","affiliation":[{"name":"CEVA Sant\u00e9 Animale , Libourne,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,9,1]]},"reference":[{"key":"2026020304290345000_jvim12141-bib-0001","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1111\/j.1939-1676.2009.0467.x","article-title":"Efficacy of spironolactone on survival in dogs with naturally occurring mitral regurgitation caused by myxomatous mitral valve disease","volume":"24","author":"Bernay","year":"2010","journal-title":"J Vet Intern Med"},{"key":"2026020304290345000_jvim12141-bib-0002","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","volume":"341","author":"Pitt","year":"1999","journal-title":"N Engl J Med"},{"key":"2026020304290345000_jvim12141-bib-0003","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1097\/00000539-200207000-00006","article-title":"Life-threatening hyperkalemia: A complication of spironolactone for heart failure in a patient with renal insufficiency","volume":"95","author":"Hu","year":"2002","journal-title":"Anesth Analg"},{"key":"2026020304290345000_jvim12141-bib-0004","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/S0002-9149(02)02581-X","article-title":"Hyperkalemia in congestive heart failure patients aged 63 to 85 years with subclinical renal disease","volume":"90","author":"Obialo","year":"2002","journal-title":"Am J Cardiol"},{"key":"2026020304290345000_jvim12141-bib-0005","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1046\/j.1365-2710.2003.00491.x","article-title":"The safety of spironolactone treatment in patients with heart failure","volume":"28","author":"Anton","year":"2003","journal-title":"J Clin Pharm Ther"},{"key":"2026020304290345000_jvim12141-bib-0006","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1136\/bmj.327.7424.1141","article-title":"Hyperkalaemia and impaired renal function in patients taking spironolactone for congestive heart failure: Retrospective study","volume":"327","author":"Svensson","year":"2003","journal-title":"Brit Med J"},{"key":"2026020304290345000_jvim12141-bib-0007","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1056\/NEJMoa040135","article-title":"Rates of hyperkalemia after publication of the randomized aldactone evaluation study","volume":"351","author":"Juurlink","year":"2004","journal-title":"N Engl J Med"},{"key":"2026020304290345000_jvim12141-bib-0008","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.cardfail.2003.10.012","article-title":"How prevalent is hyperkalemia and renal dysfunction during treatment with spironolactone in patients with congestive heart failure?","volume":"10","author":"Svensson","year":"2004","journal-title":"J Card Fail"},{"key":"2026020304290345000_jvim12141-bib-0009","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/j.ahj.2004.10.005","article-title":"Spironolactone-induced renal insufficiency and hyperkalemia in patients with heart failure","volume":"148","author":"Tamirisa","year":"2004","journal-title":"Am Heart J"},{"key":"2026020304290345000_jvim12141-bib-0010","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1016\/j.jacc.2007.07.067","article-title":"Incidence and predictors of hyperkalemia in patients with heart failure: An analysis of the CHARM Program","volume":"50","author":"Desai","year":"2007","journal-title":"J Am Coll Cardiol"},{"key":"2026020304290345000_jvim12141-bib-0011","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1002\/clc.20284","article-title":"Safety of spironolactone use in ambulatory heart failure patients","volume":"31","author":"Lopes","year":"2008","journal-title":"Clin Cardiol"},{"key":"2026020304290345000_jvim12141-bib-0012","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.cardfail.2010.01.001","article-title":"Renal function in outpatients with chronic heart failure","volume":"16","author":"Waldum","year":"2010","journal-title":"J Card Fail"},{"key":"2026020304290345000_jvim12141-bib-0013","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/j.jacc.2005.06.010","article-title":"The adequacy of laboratory monitoring in patients treated with spironolactone for congestive heart failure","volume":"46","author":"Shah","year":"2005","journal-title":"J Am Coll Cardiol"},{"key":"2026020304290345000_jvim12141-bib-0014","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.4065\/80.12.1623","article-title":"Aldosterone receptor antagonists in the medical management of chronic heart failure","volume":"80","author":"Tang","year":"2005","journal-title":"Mayo Clin Proc"},{"key":"2026020304290345000_jvim12141-bib-0015","first-page":"F381","article-title":"Renal and systemic acid-base effects of chronic spironolactone administration","volume":"240","author":"Hulter","year":"1981","journal-title":"Am J Physiol"},{"key":"2026020304290345000_jvim12141-bib-0016","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.jvc.2007.10.002","article-title":"Effect of spironolactone on diuresis and urine sodium and potassium excretion in healthy dogs","volume":"9","author":"Jeunesse","year":"2007","journal-title":"J Vet Cardiol"},{"key":"2026020304290345000_jvim12141-bib-0017","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.jvc.2007.08.002","article-title":"Influence of combined angiotensin-converting enzyme inhibitors and spironolactone on serum K+, Mg 2 + , and Na+ concentrations in small dogs with degenerative mitral valve disease","volume":"9","author":"Thomason","year":"2007","journal-title":"J Vet Cardiol"},{"key":"2026020304290345000_jvim12141-bib-0018","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.2460\/ajvr.68.10.1058","article-title":"Effects of oral administration of furosemide and torsemide in healthy dogs","volume":"68","author":"Hori","year":"2007","journal-title":"Am J Vet Res"},{"key":"2026020304290345000_jvim12141-bib-0019","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1111\/j.1939-1676.2009.0367.x","article-title":"Acute effect of pimobendan and furosemide on the circulating renin-angiotensin-aldosterone system in healthy dogs","volume":"23","author":"Sayer","year":"2009","journal-title":"J Vet Intern Med"},{"key":"2026020304290345000_jvim12141-bib-0020","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1111\/j.1365-2885.2010.01235.x","article-title":"Lack of efficacy of low-dose spironolactone as adjunct treatment to conventional congestive heart failure treatment in dogs","volume":"34","author":"Schuller","year":"2011","journal-title":"J Vet Pharmacol Ther"},{"key":"2026020304290345000_jvim12141-bib-0021","doi-asserted-by":"crossref","first-page":"194","DOI":"10.2460\/javma.1995.206.02.194","article-title":"Vertebral scale system to measure canine heart size in radiographs","volume":"206","author":"Buchanan","year":"1995","journal-title":"J Am Vet Med Assoc"},{"key":"2026020304290345000_jvim12141-bib-0022","volume-title":"Textbook of Canine and Feline Cardiology: Principles and Clinical Practice","author":"Fox","year":"1999","edition":"2nd ed"},{"key":"2026020304290345000_jvim12141-bib-0023","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1111\/j.1365-2885.2009.01130.x","article-title":"A preclinical pharmacokinetic and pharmacodynamic approach to determine the dose of spironolactone for treatment of congestive heart failure in dog","volume":"33","author":"Guyonnet","year":"2010","journal-title":"J Vet Pharmacol Therap"},{"key":"2026020304290345000_jvim12141-bib-0024","volume-title":"VICH Topic GL9 (GCP). Guideline on Good Clinical Practices","author":"CVMP\/VICH\/595\/98-FINAL","year":"2000"},{"key":"2026020304290345000_jvim12141-bib-0025","volume-title":"Guidance Notes on the Use of VeDDRA Terminology for Reporting Suspected Adverse Reactions in Animals and Humans","author":"EMA\/CVMP\/PhVWP\/288284\/2007"},{"key":"2026020304290345000_jvim12141-bib-0026","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1111\/j.1939-1676.2007.tb03047.x","article-title":"Azotemia and glomerular filtration rate in dogs with chronic valvular disease","volume":"21","author":"Nicolle","year":"2007","journal-title":"J Vet Intern Med"},{"key":"2026020304290345000_jvim12141-bib-0027","volume-title":"Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory; Approved Guidelines, CLSI document C28-A3, Vol. 28, No. 3","author":"Clinical and Laboratory Standards Institute (CLSI)","year":"2008","edition":"3rd ed"},{"key":"2026020304290345000_jvim12141-bib-0028","doi-asserted-by":"crossref","first-page":"654","DOI":"10.2460\/javma.2002.221.654","article-title":"Effects of long-term administration of enalapril on clinical indicators of renal function in dogs with compensated mitral regurgitation","volume":"221","author":"Atkins","year":"2002","journal-title":"J Am Vet Med Assoc"},{"key":"2026020304290345000_jvim12141-bib-0029","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/S1760-2734(06)70059-5","article-title":"Long-term tolerability of benazepril in dogs with congestive heart failure","volume":"6","author":"Pouchelon","year":"2004","journal-title":"J Vet Cardiol"},{"key":"2026020304290345000_jvim12141-bib-0030","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1161\/CIRCULATIONAHA.105.580506","article-title":"Renal function as a predictor of outcome in a broad spectrum of patients with heart failure","volume":"113","author":"Hillege","year":"2006","journal-title":"Circulation"},{"key":"2026020304290345000_jvim12141-bib-0031","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1097\/01.ASN.0000115398.92270.30","article-title":"Overview: Increased cardiovascular risk in patients with minor renal dysfunction: An emerging issue with far-reaching consequences","volume":"15","author":"Ritz","year":"2004","journal-title":"J Am Soc Nephrol"},{"key":"2026020304290345000_jvim12141-bib-0032","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1038\/ki.2011.48","article-title":"Mineralocorticoid receptor activation and blockade: An emerging paradigm in chronic kidney disease","volume":"79","author":"Bertocchio","year":"2011","journal-title":"Kidney Int"},{"key":"2026020304290345000_jvim12141-bib-0033","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1042\/cs0580227","article-title":"Effect of spironolactone on aldosterone regulation in man","volume":"58","author":"Gaillard","year":"1980","journal-title":"Clin Sci (Lond)"},{"key":"2026020304290345000_jvim12141-bib-0034","first-page":"58","article-title":"Effect of spironolactone administration on plasma and urinary aldosterone in man and the rat","volume":"17","author":"Vallotton","year":"1980","journal-title":"Prog Biochem Pharmacol"}],"container-title":["Journal of Veterinary Internal Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjvim.12141","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjvim.12141","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jvim\/article-pdf\/27\/5\/1083\/66685063\/jvim12141.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jvim\/article-pdf\/27\/5\/1083\/66685063\/jvim12141.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T09:29:24Z","timestamp":1770110964000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jvim\/article\/27\/5\/1083\/8451980"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,9,1]]},"references-count":34,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2013,9,1]]}},"URL":"https:\/\/doi.org\/10.1111\/jvim.12141","relation":{},"ISSN":["1939-1676"],"issn-type":[{"value":"1939-1676","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2013,9]]},"published":{"date-parts":[[2013,9,1]]}}}