{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T05:54:19Z","timestamp":1793426059990,"version":"4.5.0"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"13","license":[{"start":{"date-parts":[[2022,9,27]],"date-time":"2022-09-27T00:00:00Z","timestamp":1664236800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2022,9,27]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Iron deficiency is common in heart failure and associated with worse outcomes. We examined the prevalence and consequences of iron deficiency in the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure) and the effect of dapagliflozin on markers of iron metabolism. We also analyzed the effect of dapagliflozin on outcomes, according to iron status at baseline.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>Iron deficiency was defined as a ferritin level &lt;100 ng\/mL or a transferrin saturation &lt;20% and a ferritin level 100 to 299 ng\/mL. Additional biomarkers of iron metabolism, including soluble transferrin receptor, erythropoietin, and hepcidin were measured at baseline and 12 months after randomization. The primary outcome was a composite of worsening heart failure (hospitalization or urgent visit requiring intravenous therapy) or cardiovascular death.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              Of the 4744 patients randomized in DAPA-HF, 3009 had ferritin and transferrin saturation measurements available at baseline, and 1314 of these participants (43.7%) were iron deficient. The rate of the primary outcome was higher in patients with iron deficiency (16.6 per 100 person-years) compared with those without (10.4 per 100 person-years;\n              <jats:italic>P<\/jats:italic>\n              &lt;0.0001). The effect of dapagliflozin on the primary outcome was consistent in iron-deficient compared with iron-replete patients (hazard ratio, 0.74 [95% CI, 0.58\u20130.92] versus 0.81 [95% CI, 0.63\u20131.03];\n              <jats:italic>P<\/jats:italic>\n              -interaction=0.59). Similar findings were observed for cardiovascular death, heart failure hospitalization, and all-cause mortality. Transferrin saturation, ferritin, and hepcidin were reduced and total iron-binding capacity and soluble transferrin receptor increased with dapagliflozin compared with placebo.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Iron deficiency was common in DAPA-HF and associated with worse outcomes. Dapagliflozin appeared to increase iron use but improved outcomes, irrespective of iron status at baseline.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Registration:<\/jats:title>\n            <jats:p>\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              ; Unique identifier: NCT03036124.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.122.060511","type":"journal-article","created":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T18:00:31Z","timestamp":1664215231000},"page":"980-994","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":142,"title":["Iron Deficiency in Heart Failure and Effect of Dapagliflozin: Findings From DAPA-HF"],"prefix":"10.1161","volume":"146","clinical-trial-number":[{"clinical-trial-number":"nct03036124","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5446-9969","authenticated-orcid":true,"given":"Kieran F.","family":"Docherty","sequence":"first","affiliation":[{"name":"British Heart Foundation Cardiovascular Research Centre, University of Glasgow, United Kingdom (K.F.D., P.W., N.S., P.S.J., J.J.V.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7970-3643","authenticated-orcid":true,"given":"Paul","family":"Welsh","sequence":"additional","affiliation":[{"name":"British Heart Foundation Cardiovascular Research Centre, University of Glasgow, United Kingdom (K.F.D., P.W., N.S., P.S.J., J.J.V.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4018-8533","authenticated-orcid":true,"given":"Subodh","family":"Verma","sequence":"additional","affiliation":[{"name":"Division of Cardiac Surgery, St Michael\u2019s Hospital, University of Toronto, Canada (S.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4775-9140","authenticated-orcid":true,"given":"Rudolf A.","family":"De Boer","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Center and University of Groningen, The Netherlands (R.A.D.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen","family":"O\u2019Meara","sequence":"additional","affiliation":[{"name":"Montreal Heart Institute, Universit\u00e9 de Montr\u00e9al, Canada (E.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1315-8176","authenticated-orcid":true,"given":"Olof","family":"Bengtsson","sequence":"additional","affiliation":[{"name":"AstraZeneca R&amp;D, Gothenburg, Sweden (O.B., A.H., A.M.L., D.L., D.J.L., M. Sj\u00f6strand)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6635-1466","authenticated-orcid":true,"given":"Lars","family":"K\u00f8ber","sequence":"additional","affiliation":[{"name":"Rigshospitalet Copenhagen University Hospital, Denmark (L.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3750-9789","authenticated-orcid":true,"given":"Mikhail N.","family":"Kosiborod","sequence":"additional","affiliation":[{"name":"Saint Luke\u2019s Mid America Heart Institute and University of Missouri-Kansas City (M.N.K.)."},{"name":"George Institute for Global Health, University of New South Wales, Sydney, Australia (M.N.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Hammarstedt","sequence":"additional","affiliation":[{"name":"AstraZeneca R&amp;D, Gothenburg, Sweden (O.B., A.H., A.M.L., D.L., D.J.L., M. Sj\u00f6strand)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Maria","family":"Langkilde","sequence":"additional","affiliation":[{"name":"AstraZeneca R&amp;D, Gothenburg, Sweden (O.B., A.H., A.M.L., D.L., D.J.L., M. Sj\u00f6strand)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3526-0614","authenticated-orcid":true,"given":"Daniel","family":"Lindholm","sequence":"additional","affiliation":[{"name":"AstraZeneca R&amp;D, Gothenburg, Sweden (O.B., A.H., A.M.L., D.L., D.J.L., M. Sj\u00f6strand)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dustin J.","family":"Little","sequence":"additional","affiliation":[{"name":"AstraZeneca R&amp;D, Gothenburg, Sweden (O.B., A.H., A.M.L., D.L., D.J.L., M. Sj\u00f6strand)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6253-9886","authenticated-orcid":true,"given":"Mikaela","family":"Sj\u00f6strand","sequence":"additional","affiliation":[{"name":"AstraZeneca R&amp;D, Gothenburg, Sweden (O.B., A.H., A.M.L., D.L., D.J.L., M. Sj\u00f6strand)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5836-972X","authenticated-orcid":true,"given":"Felipe A.","family":"Martinez","sequence":"additional","affiliation":[{"name":"George Institute for Global Health, University of New South Wales, Sydney, Australia (M.N.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3391-7064","authenticated-orcid":true,"given":"Piotr","family":"Ponikowski","sequence":"additional","affiliation":[{"name":"Wroclaw Medical University, Poland (P.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0691-3359","authenticated-orcid":true,"given":"Marc S.","family":"Sabatine","sequence":"additional","affiliation":[{"name":"TIMI (Thrombolysis in Myocardial Infarction) Study Group, Cardiovascular Division, Brigham and Women\u2019s Hospital, and Harvard Medical School, Boston, MA (M.S.S., D.A.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9589-5382","authenticated-orcid":true,"given":"David A.","family":"Morrow","sequence":"additional","affiliation":[{"name":"TIMI (Thrombolysis in Myocardial Infarction) Study Group, Cardiovascular Division, Brigham and Women\u2019s Hospital, and Harvard Medical School, Boston, MA (M.S.S., D.A.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4271-2466","authenticated-orcid":true,"given":"Morten","family":"Schou","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark (M. Schou)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3698-9597","authenticated-orcid":true,"given":"Scott D.","family":"Solomon","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital, Boston, MA (S.D.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1604-2593","authenticated-orcid":true,"given":"Naveed","family":"Sattar","sequence":"additional","affiliation":[{"name":"British Heart Foundation Cardiovascular Research Centre, University of Glasgow, United Kingdom (K.F.D., P.W., N.S., P.S.J., J.J.V.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4306-5317","authenticated-orcid":true,"given":"Pardeep S.","family":"Jhund","sequence":"additional","affiliation":[{"name":"British Heart Foundation Cardiovascular Research Centre, University of Glasgow, United Kingdom (K.F.D., P.W., N.S., 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