{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T01:24:28Z","timestamp":1783819468409,"version":"3.55.0"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2021,11,21]],"date-time":"2021-11-21T00:00:00Z","timestamp":1637452800000},"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":["European J of Heart Fail"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Outpatient treatment for the worsening of signs and symptoms of heart failure (HF) is usually not incorporated in the main outcomes of HF trials. Patients with HF and a preserved ejection fraction (HFpEF) may experience frequent episodes of outpatient worsening HF. The aim of this study was to evaluate the frequency, prognostic impact, and the effect of spironolactone on outpatient diuretic intensification (ODI), among 1767 patients enrolled in TOPCAT\u2010Americas.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      Time\u2010updated Cox models and win ratio analysis. ODI was defined by a post\u2010randomization loop diuretic dose increase or new initiation. The median follow\u2010up was 2.9\u2009years. At baseline, 1362 (77%) patients were taking loop diuretics. During the follow\u2010up, 685 (38.8%) patients experienced ODI, which was associated with a higher risk of subsequent cardiovascular events and death [adjusted hazard ratio (HR) for HF hospitalization or cardiovascular death 1.67, 95% confidence interval (CI) 1.36\u20132.04; HR for cardiovascular death 2.17, 95% CI 1.64\u20132.87); and HR for all\u2010cause mortality 1.75, 95% CI 1.41\u20132.16] (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u20090.001 for all outcomes). Adding ODI to the composite of HF hospitalization or cardiovascular death increased the event rate by three\u2010fold in the placebo group (from 10.4 to 29.9 events per 100 person\u2010years). Spironolactone treatment led to a 26% relative reduction of the extended composite of ODI or HF hospitalization or cardiovascular death (HR 0.74, 95% CI 0.65\u20130.85;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u20090.001) compared with a 16% relative reduction of HF hospitalization or cardiovascular death (HR 0.84, 95% CI 0.70\u20130.99;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u20090.044). Using win ratio provided similar estimates.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In HFpEF, ODI was frequent and independently associated with subsequent cardiovascular events. Spironolactone significantly reduced an extended composite outcome incorporating ODI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.2376","type":"journal-article","created":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T20:18:32Z","timestamp":1636489112000},"page":"378-384","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Outpatient diuretic intensification as endpoint in heart failure with preserved ejection fraction trials: an analysis from\n                    <scp>TOPCAT<\/scp>"],"prefix":"10.1093","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2304-6138","authenticated-orcid":false,"given":"Jo\u00e3o Pedro","family":"Ferreira","sequence":"first","affiliation":[{"name":"Inserm, Centre d'Investigations Cliniques Plurith\u00e9matique 1433, and Inserm U1116, CHRU, F\u2010CRIN INI\u2010CRCT (Cardiovascular and Renal Clinical Trialists) Universit\u00e9 de Lorraine  Nancy France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiankang","family":"Liu","sequence":"additional","affiliation":[{"name":"Cardiovascular Division Brigham and Women's Hospital  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian L.","family":"Claggett","sequence":"additional","affiliation":[{"name":"Cardiovascular Division Brigham and Women's Hospital  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orly","family":"Vardeny","sequence":"additional","affiliation":[{"name":"Minneapolis VA Center for Care Delivery and Outcomes Research University of Minnesota  Minneapolis MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertram","family":"Pitt","sequence":"additional","affiliation":[{"name":"Division of Cardiology University of Michigan  Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc A.","family":"Pfeffer","sequence":"additional","affiliation":[{"name":"Cardiovascular Division Brigham and Women's Hospital  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott D.","family":"Solomon","sequence":"additional","affiliation":[{"name":"Cardiovascular Division Brigham and Women's Hospital  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faiez","family":"Zannad","sequence":"additional","affiliation":[{"name":"Inserm, Centre d'Investigations Cliniques Plurith\u00e9matique 1433, and Inserm U1116, CHRU, F\u2010CRIN INI\u2010CRCT (Cardiovascular and Renal Clinical Trialists) Universit\u00e9 de Lorraine  Nancy 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