{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T22:01:36Z","timestamp":1785276096460,"version":"3.55.0"},"reference-count":0,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>This report describes the design and baseline characteristics of the SPIRIT-HF trial and compares them with prior heart failure with mildly reduced or preserved ejection fraction (HFpEF\/HFmrEF) trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p>In this multicenter, double-blind, placebo-controlled phase III trial, 730 patients aged \u226550 years with left ventricular ejection fraction (LVEF) \u226540%, New York Heart Association (NYHA) class II-IV symptoms, and either elevated N-terminal-pro-B-type natriuretic peptide (NT-proBNP) or HF hospitalization within 12 months were randomized 1:1 to spironolactone or placebo. The primary endpoint is a composite of rate of total (first and recurrent) HF hospitalizations and cardiovascular death within 24 months from randomization, which will be analyzed using the LWYY model. Secondary endpoints in a hierarchical order include total HF hospitalizations, CV hospitalizations, all hospitalizations, and cardiovascular death within 24 months from randomization. Results will first be analyzed based on the SPIRIT-HF dataset only. Then, a pre-specified individual participant data meta-analysis combining SPIRIT-HF and TOPCAT Americas will be conducted to refine treatment effect estimates. The median age of the patients enrolled in the SPIRIT-HF was 77.8 years, and 52% were women. The median LVEF was 55% (50-60), with 18% of patients having a LVEF between 40-49%. In SPIRIT-HF, prior HF hospitalization was similarly frequent (46.4% vs. 55%), but NT-proBNP was slightly higher (970 vs. 900 pg\/ml) compared to TOPCAT Americas. However, the proportion of patients with NYHA class III (33% vs. 35%), patients with comorbidities such as atrial fibrillation at baseline electrocardiogram (25% vs. 25%) and chronic kidney disease (50% vs. 48%); and background therapy, such as beta-blockers (76% vs. 79%), and diuretics (83% vs. 89%), including loop diuretics (69% vs. 78%), were similar between SPIRIT-HF and TOPCAT Americas. Compared with prior HFpEF\/HFmrEF trials, SPIRIT-HF patients demonstrated a higher risk with a similar proportion of patients with recent HF hospitalization (46.4%) and slightly higher NT-proBNP concentrations (970 pg\/ml) at baseline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>SPIRIT-HF addresses key evidence gaps for spironolactone in high-risk HFpEF\/HFmrEF, and could inform guideline recommendations on MRA use in this cohort.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ejhf\/xuag222","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T11:19:25Z","timestamp":1785151165000},"source":"Crossref","is-referenced-by-count":0,"title":["Spironolactone in the Treatment of Heart Failure with Mildly Reduced or Preserved Ejection Fraction: Design and Baseline Characteristics of the SPIRIT-HF-DZHK08 Trial"],"prefix":"10.1093","author":[{"given":"Daniela","family":"Zurkan","sequence":"first","affiliation":[{"name":"Deutsches Herzzentrum der Charit\u00e9, Klinik f\u00fcr Kardiologie, Angiologie und Intensivmedizin, Department of Cardiology, Angiology and Intensive Care Medicine , Augustenburger Platz 1, 13353 Berlin ,","place":["Germany"]},{"name":"Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin , Charit\u00e9platz 1, 10117 Berlin ,","place":["Germany"]},{"name":"DZHK, German Centre for Cardiovascular Research partner site Berlin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burkert","family":"Pieske","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, University Medicine Rostock , Rostock ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3116-9450","authenticated-orcid":false,"given":"Johannes","family":"Petutschnigg","sequence":"additional","affiliation":[{"name":"Deutsches Herzzentrum der Charit\u00e9, Klinik f\u00fcr Kardiologie, Angiologie und Intensivmedizin, Department of Cardiology, Angiology and Intensive Care Medicine , Augustenburger Platz 1, 13353 Berlin ,","place":["Germany"]},{"name":"Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin , Charit\u00e9platz 1, 10117 Berlin ,","place":["Germany"]},{"name":"DZHK, German Centre for Cardiovascular Research partner site Berlin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7414-4056","authenticated-orcid":false,"given":"Nicolas","family":"Verheyen","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Medical University of Graz ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Shahzeb","family":"Khan","sequence":"additional","affiliation":[{"name":"Baylor Scott and White Research Institute, Baylor Scott and White Health , Dallas, TX ,","place":["USA"]},{"name":"Baylor Scott and White-The Heart Hospital , Plano, TX ,","place":["USA"]},{"name":"Department of Medicine, Baylor College of Medicine , Temple, TX ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2304-6138","authenticated-orcid":false,"given":"Joao Pedro","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, Centre d'Investigations Cliniques Plurith\u00e9matique 1433 and Inserm U1116, CHRU Nancy, FCRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists) , Nancy ,","place":["France"]},{"name":"Department of Physiology and Cardiothoracic Surgery, Cardiovascular R&D Centre - UnIC@RISE, Faculty of Medicine of the University of Porto, Porto, Portugal; Heart Failure Clinic, Internal Medicine Department, Unidade Local de Sa\u00fade de Gaia\/Espinho , Gaia ,","place":["Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Girerd","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, Centre d'Investigations Cliniques Plurith\u00e9matique 1433 and Inserm U1116, CHRU Nancy, FCRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists) , Nancy ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Biegus","sequence":"additional","affiliation":[{"name":"Institute of Heart Diseases, University Hospital of Wroclaw Medical University , Wroclaw ,","place":["Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Felix","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine B, University Medicine Greifswald , Greifswald ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerd","family":"Hasenfu\u00df","sequence":"additional","affiliation":[{"name":"Clinic for Cardiology and Pneumology, University Medical Center G\u00f6ttingen, German Centre for Cardiovascular Research (DZHK), partner site Lower Saxony , G\u00f6ttingen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6906-2643","authenticated-orcid":false,"given":"Arend","family":"Mosterd","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Meander Medical Center , Amersfoort ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertram","family":"Pitt","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Cardiovascular Medicine University of Michigan Frankel Cardiovascular Center \u00a0 Ann Arbor MN \u00a0","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Ponikowski","sequence":"additional","affiliation":[{"name":"Institute of Heart Diseases, University Hospital of Wroclaw Medical University , Wroclaw ,","place":["Poland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5655-8201","authenticated-orcid":false,"given":"Sanjiv","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Northwestern University School of Medicine , Chicago, Illinois ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Trippel","sequence":"additional","affiliation":[{"name":"Deutsches Herzzentrum der Charit\u00e9, Klinik f\u00fcr Kardiologie, Angiologie und Intensivmedizin, Department of Cardiology, Angiology and Intensive Care Medicine , Augustenburger Platz 1, 13353 Berlin ,","place":["Germany"]},{"name":"Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin , Charit\u00e9platz 1, 10117 Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7456-1570","authenticated-orcid":false,"given":"Faiez","family":"Zannad","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, Centre d'Investigations Cliniques Plurith\u00e9matique 1433 and Inserm U1116, CHRU Nancy, FCRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists) , Nancy ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius","family":"Placzek","sequence":"additional","affiliation":[{"name":"Department of Medical Statistics, University Medical Center G\u00f6ttingen, German Centre for Cardiovascular Research (DZHK) , partner site Lower Saxony, G\u00f6ttingen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5347-7441","authenticated-orcid":false,"given":"Tim","family":"Friede","sequence":"additional","affiliation":[{"name":"Department of Medical Statistics, University Medical Center G\u00f6ttingen, German Centre for Cardiovascular Research (DZHK) , partner site Lower Saxony, G\u00f6ttingen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan D","family":"Anker","sequence":"additional","affiliation":[{"name":"Deutsches Herzzentrum der Charit\u00e9, Klinik f\u00fcr Kardiologie, Angiologie und Intensivmedizin, Department of Cardiology, Angiology and Intensive Care Medicine , Augustenburger Platz 1, 13353 Berlin ,","place":["Germany"]},{"name":"Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin , Charit\u00e9platz 1, 10117 Berlin ,","place":["Germany"]},{"name":"DZHK, German Centre for Cardiovascular Research partner site Berlin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Edelmann","sequence":"additional","affiliation":[{"name":"Deutsches Herzzentrum der Charit\u00e9, Klinik f\u00fcr Kardiologie, Angiologie und Intensivmedizin, Department of Cardiology, Angiology and Intensive Care Medicine , Augustenburger Platz 1, 13353 Berlin ,","place":["Germany"]},{"name":"Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin , Charit\u00e9platz 1, 10117 Berlin ,","place":["Germany"]},{"name":"DZHK, German Centre for Cardiovascular Research partner site Berlin"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,7,28]]},"container-title":["European Journal of Heart 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