{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T10:53:38Z","timestamp":1786791218050,"version":"build-2736575974"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2020,6,19]],"date-time":"2020-06-19T00:00:00Z","timestamp":1592524800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"},{"start":{"date-parts":[[2020,6,19]],"date-time":"2020-06-19T00:00:00Z","timestamp":1592524800000},"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":[[2020,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Spironolactone up-titration may be limited by side effects that could be minimized at lower than target doses, but whether lower than target doses remain efficacious is unknown. In TOPCAT, spironolactone (or placebo) were started at 15\u2009mg\/day, and increased up to a maximum of 45\u2009mg\/day. The prognostic implications related to spironolactone dose are yet to be reported. We aimed to assess the average spironolactone\/placebo doses provided during the trial, overall and within high-risk subgroups (e.g. elderly, renal dysfunction, high potassium); discontinuation rates; and the efficacy of lower than target doses in heart failure with preserved ejection fraction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Overall, 1767 patients from \u2018TOPCAT-Americas\u2019 were included. Linear, logistic and Cox regressions were applied. Patients randomized to spironolactone received lower doses than placebo: 22.5 (15.0\u201327.5) mg\/day vs. 27.5 (17.5\u201327.5) mg\/day (P\u2009&amp;lt;\u20090.001). Patients aged \u226575\u2009years, with an estimated glomerular filtration rate \u226460\u2009mL\/min\/1.73\u2009m2, and with potassium levels &amp;gt;4.5\u2009mmol\/L, received lower spironolactone doses (median\u2009\u2248\u200920\u2009mg\/day). This pattern of dose differences was not observed in patients taking placebo, where the between-subgroup placebo doses were similar (spironolactone\u2013placebo by subgroup Pinteraction\u2009&amp;lt;\u20090.05). Among patients taking spironolactone, 25.4% discontinued the drug during the first year, compared with 18.3% of the patients taking placebo (P\u2009&amp;lt;\u20090.001). Discontinuation rates in the aforementioned high-risk subgroups reached 30% during the first year. Spironolactone reduced the primary outcome of heart failure hospitalization\/cardiovascular death without significant heterogeneity between the study subgroups (Pinteraction\u2009&amp;gt;\u20090.1). Spironolactone discontinuation was associated with a two to fourfold higher risk of subsequent events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Spironolactone (but not placebo) was used at lower doses among the elderly, those with renal dysfunction and with higher potassium levels. The effect of spironolactone was homogeneous across these subgroups. In patients unable to tolerate target doses, a low-dose strategy should be preferred to stopping treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.1909","type":"journal-article","created":{"date-parts":[[2020,5,26]],"date-time":"2020-05-26T00:03:52Z","timestamp":1590451432000},"page":"1615-1624","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Spironolactone Dose in Heart Failure with Preserved Ejection Fraction: Findings from TOPCAT"],"prefix":"10.1093","volume":"22","author":[{"given":"Jo\u00e3o Pedro","family":"Ferreira","sequence":"first","affiliation":[{"name":"Universit\u00e9 de Lorraine, Centre d\u2019Investigation Clinique-Plurith\u00e9matique, CHRU Nancy, INSERM U1116, and FCRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists) , Nancy ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Rossello","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Centro Nacional de Investigaciones Cardiovasculares Carlos III , Madrid ,","place":["Spain"]},{"name":"Department of Cardiology, Health Research Institute of the Balearic Islands (IdISBa), University Hospital Son Espases , Palma ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart J.","family":"Pocock","sequence":"additional","affiliation":[{"name":"London School of Hygiene and Tropical Medicine , London ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Rossignol","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Lorraine, Centre d\u2019Investigation Clinique-Plurith\u00e9matique, CHRU Nancy, INSERM U1116, and FCRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists) , Nancy ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian L.","family":"Claggett","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Lucien","family":"Rouleau","sequence":"additional","affiliation":[{"name":"Montreal Heart Institute , Montreal ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott D.","family":"Solomon","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertram","family":"Pitt","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Michigan School of Medicine , Ann Arbor, 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