{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T14:20:04Z","timestamp":1789914004245,"version":"4.0.1"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>In 3 randomized controlled trials in heart failure (HF), mineralocorticoid receptor antagonists reduced mortality. The net benefit from randomized controlled trials may not be generalizable, and eplerenone was, but spironolactone was not, studied in mild HF. We tested the hypothesis that spironolactone is associated with reduced mortality also in a broad unselected contemporary population with HF and reduced ejection fraction, in particular New York Heart Association (NYHA) I\u2013II.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              We prospectively studied 18 852 patients (age 71\u00b112 years; 28% women) with NYHA I\u2013IV and ejection fraction &lt;40% who were registered in the Swedish Heart Failure Registry between 2000 and 2012 and who were (n=6551) or were not (n=12 301) treated with spironolactone. We derived propensity scores for spironolactone treatment based on 41 covariates. We assessed survival by Cox regression with adjustment for propensity scores and with matching based on propensity score. We performed sensitivity and residual confounding analyses and analyzed the NYHA I\u2013II and III\u2013IV subgroups separately. One-year survival was 83% versus 84% in treated versus untreated patients (log rank\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001). After adjustment for propensity scores, the hazard ratio for spironolactone was 1.05 (95% confidence interval, 1.00\u20131.11;\n              <jats:italic>P<\/jats:italic>\n              =0.054). Spironolactone interacted with NYHA (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001). In the NYHA I\u2013II subgroup, after adjustment for propensity scores, the hazard ratio for spironolactone was 1.11 (95% confidence interval, 1.02\u20131.21;\n              <jats:italic>P<\/jats:italic>\n              =0.019).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>In an unselected contemporary population of HF with reduced ejection fraction, spironolactone was not associated with reduced mortality. The net benefits of spironolactone may be lower outside the clinical trial setting and in milder HF.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circheartfailure.112.000115","type":"journal-article","created":{"date-parts":[[2013,2,6]],"date-time":"2013-02-06T02:05:32Z","timestamp":1360116332000},"page":"174-183","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":43,"title":["Association of Spironolactone Use With All-Cause Mortality in Heart Failure"],"prefix":"10.1161","volume":"6","author":[{"given":"Lars H.","family":"Lund","sequence":"first","affiliation":[{"name":"From the Department of Medicine, Karolinska Institutet, Stockholm, Sweden (L.H.L., M.E.); Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden (L.H.L.); Uppsala Clinical Research Center, Uppsala, Sweden (B.S.); Department of Medical Sciences, Uppsala University, Uppsala, Sweden (H.M., P.H.); Department of Medicine, Link\u00f6ping University, Link\u00f6ping, Sweden (U.D.); and Department of Cardiology, University Hospital Link\u00f6ping, Link\u00f6ping, Sweden (U.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bodil","family":"Svennblad","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Karolinska Institutet, Stockholm, Sweden (L.H.L., M.E.); Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden (L.H.L.); Uppsala Clinical Research Center, Uppsala, Sweden (B.S.); Department of Medical Sciences, Uppsala University, Uppsala, Sweden (H.M., P.H.); Department of Medicine, Link\u00f6ping University, Link\u00f6ping, Sweden (U.D.); and Department of Cardiology, University Hospital Link\u00f6ping, Link\u00f6ping, Sweden (U.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e5kan","family":"Melhus","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Karolinska Institutet, Stockholm, Sweden (L.H.L., M.E.); Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden (L.H.L.); Uppsala Clinical Research Center, Uppsala, Sweden (B.S.); Department of Medical Sciences, Uppsala University, Uppsala, Sweden (H.M., P.H.); Department of Medicine, Link\u00f6ping University, Link\u00f6ping, Sweden (U.D.); and Department of Cardiology, University Hospital Link\u00f6ping, Link\u00f6ping, Sweden (U.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e4r","family":"Hallberg","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Karolinska Institutet, Stockholm, Sweden (L.H.L., M.E.); Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden (L.H.L.); Uppsala Clinical Research Center, Uppsala, Sweden (B.S.); Department of Medical Sciences, Uppsala University, Uppsala, Sweden (H.M., P.H.); Department of Medicine, Link\u00f6ping University, Link\u00f6ping, Sweden (U.D.); and Department of Cardiology, University Hospital Link\u00f6ping, Link\u00f6ping, Sweden (U.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf","family":"Dahlstr\u00f6m","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Karolinska Institutet, Stockholm, Sweden (L.H.L., M.E.); Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden (L.H.L.); Uppsala Clinical Research Center, Uppsala, Sweden (B.S.); Department of Medical Sciences, Uppsala University, Uppsala, Sweden (H.M., P.H.); Department of Medicine, Link\u00f6ping University, Link\u00f6ping, Sweden (U.D.); and Department of Cardiology, University Hospital Link\u00f6ping, Link\u00f6ping, Sweden (U.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"Edner","sequence":"additional","affiliation":[{"name":"From the Department of Medicine, Karolinska Institutet, Stockholm, Sweden (L.H.L., M.E.); Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden (L.H.L.); Uppsala Clinical Research Center, Uppsala, Sweden (B.S.); Department of Medical Sciences, Uppsala University, Uppsala, Sweden (H.M., P.H.); Department of Medicine, Link\u00f6ping University, Link\u00f6ping, Sweden (U.D.); and Department of Cardiology, University Hospital Link\u00f6ping, Link\u00f6ping, Sweden (U.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199909023411001"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa030207"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1009492"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.553370"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehs104"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinternmed.2011.31"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa040135"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2012.14795"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfp175"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2010.1949"},{"key":"e_1_3_3_12_2","first-page":"1","article-title":"Mice: Multivariate imputation by chained equations in r.","volume":"45","author":"van Buuren S","year":"2011","unstructured":"van Buuren S, Groothuis-Oudshoorn K. 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