{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T18:41:01Z","timestamp":1788892861133,"version":"build-2803163510"},"reference-count":18,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2023,8,16]],"date-time":"2023-08-16T00:00:00Z","timestamp":1692144000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"},{"start":{"date-parts":[[2023,8,16]],"date-time":"2023-08-16T00:00:00Z","timestamp":1692144000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>In patients with acute heart failure (AHF), the addition of hydrochlorothiazide (HCTZ) to furosemide improved diuretic response in the CLOROTIC trial. This work aimed to evaluate if these effects differ across the estimated glomerular filtration rate (eGFR) spectrum.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>This post-hoc analysis of the CLOROTIC trial analysed 230 patients with AHF and explored the influence of eGFR on primary and secondary endpoints. The median eGFR was 43\u2009ml\/min\/1.73\u2009m2 (range 14\u2013109) and 23% had eGFR \u226560\u2009ml\/min\/1.73\u2009m2 (group 1), 24% from 45 to 59\u2009ml\/min\/1.73\u2009m2 (group 2), and 53% &amp;lt;45\u2009ml\/min\/1.73\u2009m2 (group 3). Patients treated with HCTZ had greatest weight loss at 72\u2009h in all three groups, but patients in group 1 had a significantly greater response (\u22122.1\u2009kg [\u22123.0 to 0.5]), compared to patients in groups 2 (\u22121.3\u2009kg [\u22122.3 to 0.2]) and 3 (\u22120.1\u2009kg [\u22121.3 to 0.4]) (p-value for interaction\u2009=\u20090.246). At 96\u2009h, the differences in weight were \u22121.8\u2009kg (\u22123.0 to \u22120.3), \u22121.4\u2009kg (\u22122.6 to 0.3), and \u22120.5\u2009kg (\u22121.3 to \u22120.1) in groups 1, 2, and 3, respectively (p-value for interaction\u2009=\u20090.256). There were no significant differences observed with the addition of HCTZ in terms of diuretic response, mortality or rehospitalizations, or safety endpoints (impaired renal function, hyponatraemia, and hypokalaemia) among the three eGFR groups (all p-values for interaction were no significant).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The addition of eGFR-adjusted doses of oral HCTZ to loop diuretics in patients with AHF improved diuretic response across the eGFR spectrum.<\/jats:p>\n                    <jats:p>Clinical Trial Registration: ClinicalTrials.gov: NCT01647932; EudraCT number: 2013\u2013001852-36.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.2988","type":"journal-article","created":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T09:10:59Z","timestamp":1691140259000},"page":"1784-1793","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Combining Loop and Thiazide Diuretics for Acute Heart Failure Across the Estimated Glomerular Filtration Rate Spectrum: A Post-Hoc Analysis of the CLOROTIC Trial"],"prefix":"10.1093","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7380-3475","authenticated-orcid":false,"given":"Joan Carles","family":"Trull\u00e0s","sequence":"first","affiliation":[{"name":"Internal Medicine Department, Hospital d'Olot i Comarcal de la Garrotxa , Girona ,","place":["Spain"]},{"name":"Tissue Repair and Regeneration Laboratory (TR2Lab), Institut de Recerca i Innovaci\u00f3 en Ci\u00e8ncies de la Vida i de la Salut a la Catalunya Central (IrisCC) , Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Lu\u00eds","family":"Morales-Rull","sequence":"additional","affiliation":[{"name":"Heart Failure Unit, Internal Medicine Department, Hospital Universitari Arnau de Villanova, Institut de Recerca Biom\u00e9dica (IRBLleida) , Lleida ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"Casado","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Hospital Universitario de Getafe , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita","family":"Carrera-Izquierdo","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Complejo Hospitalario de Soria , Soria ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"S\u00e1nchez-Marteles","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Hospital Cl\u00ednico Universitario \u2018Lozano Blesa\u2019 , Zaragoza ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Conde-Martel","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Hospital Universitario de Gran Canaria Dr. Negr\u00edn , Las Palmas de Gran Canaria ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melit\u00f3n Francisco","family":"D\u00e1vila-Ramos","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Hospital Universitario Nuestra Se\u00f1ora de la Candelaria , Santa Cruz de Tenerife ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pau","family":"Ll\u00e1cer","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Hospital de Manises , Manises ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prado","family":"Salamanca-Bautista","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Hospital Universitario Virgen Macarena, Universidad de Sevilla , Sevilla ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Chivite","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Hospital Universitari de Bellvitge, IDIBELL , Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Jordana-Comajuncosa","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Corporaci\u00f3 Sanitaria Parc Taul\u00ed , Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Villalonga","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Hospital Universitari Son Espases , Palma de Mallorca ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Inmaculada","family":"P\u00e1ez-Rubio","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Complejo Hospitalario de Huelva, Hospital Juan Ram\u00f3n Jim\u00e9nez , Huelva ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu\u00eds","family":"Manzano","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Hospital Universitario Ram\u00f3n y Cajal, IRYCIS, Universidad de Alcal\u00e1 , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesc","family":"Formiga","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Hospital Universitari de Bellvitge, IDIBELL , Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,8,16]]},"reference":[{"key":"2026010913111302800_ejhf2988-bib-0001","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1093\/eurheartj\/ehac689","article-title":"Combining loop with thiazide diuretics for decompensated heart failure: The CLOROTIC trial","volume":"44","author":"Trullas","year":"2023","journal-title":"Eur Heart J"},{"key":"2026010913111302800_ejhf2988-bib-0002","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.cardfail.2015.11.003","article-title":"Rationale and design of the \u201cSafety and Efficacy of the Combination of Loop with Thiazide-Type Diuretics in Patients with Decompensated Heart Failure (CLOROTIC) trial:\u201d A double-blind, randomized, placebo-controlled study to determine the effect of combined diuretic therapy (loop diuretics with thiazide-type diuretics) among patients with decompensated heart failure","volume":"22","author":"Trull\u00e0s","year":"2016","journal-title":"J Card Fail"},{"key":"2026010913111302800_ejhf2988-bib-0003","doi-asserted-by":"crossref","first-page":"886","DOI":"10.7326\/0003-4819-114-10-886","article-title":"The physiologic basis of diuretic synergism: Its role in treating diuretic resistance","volume":"114","author":"Ellison","year":"1991","journal-title":"Ann Intern Med"},{"key":"2026010913111302800_ejhf2988-bib-0004","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":"2026010913111302800_ejhf2988-bib-0005","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1161\/01.CIR.23.2.200","article-title":"Effects of reduced glomerular filtration rate on responsiveness to chlorothiazide and mercurial diuretics","volume":"23","author":"Reubi","year":"1961","journal-title":"Circulation"},{"key":"2026010913111302800_ejhf2988-bib-0006","doi-asserted-by":"crossref","first-page":"2507","DOI":"10.1056\/NEJMoa2110730","article-title":"Chlorthalidone for hypertension in advanced chronic kidney disease","volume":"385","author":"Agarwal","year":"2021","journal-title":"N Engl J Med"},{"key":"2026010913111302800_ejhf2988-bib-0007","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1016\/j.jacc.2019.12.059","article-title":"Diuretic therapy for patients with heart failure: JACC state-of-the-art review","volume":"75","author":"Felker","year":"2020","journal-title":"J Am Coll Cardiol"},{"key":"2026010913111302800_ejhf2988-bib-0008","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1056\/NEJMoa2203094","article-title":"Acetazolamide in acute decompensated heart failure with volume overload","volume":"387","author":"Mullens","year":"2022","journal-title":"N Engl J Med"},{"key":"2026010913111302800_ejhf2988-bib-0009","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1056\/NEJMoa1005419","article-title":"Diuretic strategies in patients with acute decompensated heart failure","volume":"364","author":"Felker","year":"2011","journal-title":"N Engl J Med"},{"key":"2026010913111302800_ejhf2988-bib-0010","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1111\/j.1751-7176.2011.00564.x","article-title":"A pilot study comparing furosemide and hydrochlorothiazide in patients with hypertension and stage 4 or 5 chronic kidney disease","volume":"14","author":"Dussol","year":"2012","journal-title":"J Clin Hypertens (Greenwich)"},{"key":"2026010913111302800_ejhf2988-bib-0011","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1056\/NEJM199808063390607","article-title":"Diuretic therapy","volume":"339","author":"Brater","year":"1998","journal-title":"N Engl J Med"},{"key":"2026010913111302800_ejhf2988-bib-0012","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":"Damman","year":"2014","journal-title":"Eur Heart J"},{"key":"2026010913111302800_ejhf2988-bib-0013","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1002\/ehf2.14221","article-title":"Implications of worsening renal function before hospitalization for acute heart failure","volume":"10","author":"Wettersten","year":"2023","journal-title":"ESC Heart Fail"},{"key":"2026010913111302800_ejhf2988-bib-0014","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1002\/ejhf.2384","article-title":"Worsening renal function in acute heart failure in the context of diuretic response","volume":"24","author":"Emmens","year":"2022","journal-title":"Eur J Heart Fail"},{"key":"2026010913111302800_ejhf2988-bib-0015","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1093\/eurheartj\/ehac784","article-title":"Time to revisit combination loop and thiazide diuretic therapy for patients with acute heart failure","volume":"44","author":"Zakeri","year":"2023","journal-title":"Eur Heart J"},{"key":"2026010913111302800_ejhf2988-bib-0016","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.1002\/ejhf.2638","article-title":"Longitudinal trajectories in renal function before and after heart failure hospitalization among patients with heart failure with preserved ejection fraction in the PARAGON-HF trial","volume":"24","author":"Chatur","year":"2022","journal-title":"Eur J Heart Fail"},{"key":"2026010913111302800_ejhf2988-bib-0017","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1093\/ckj\/sfac198","article-title":"Thiazide diuretics are back in CKD: The case of chlorthalidone","volume":"16","author":"Minutolo","year":"2022","journal-title":"Clin Kidney J"},{"key":"2026010913111302800_ejhf2988-bib-0018","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1002\/ejhf.1369","article-title":"The use of diuretics in heart failure with congestion \u2013 a position statement from the Heart Failure Association of the European Society of Cardiology","volume":"21","author":"Mullens","year":"2019","journal-title":"Eur J Heart Fail"}],"container-title":["European Journal of Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/25\/10\/1784\/65556354\/eurjhf_25_10_1784.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/25\/10\/1784\/65556354\/eurjhf_25_10_1784.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T18:14:01Z","timestamp":1767982441000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eurjhf\/article\/25\/10\/1784\/8342862"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,16]]},"references-count":18,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,8,16]]},"published-print":{"date-parts":[[2023,10,1]]}},"URL":"https:\/\/doi.org\/10.1002\/ejhf.2988","relation":{},"ISSN":["1388-9842","1879-0844"],"issn-type":[{"value":"1388-9842","type":"print"},{"value":"1879-0844","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,10]]},"published":{"date-parts":[[2023,8,16]]},"assertion":[{"value":"2023-04-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}