{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T12:20:04Z","timestamp":1768738804867,"version":"3.49.0"},"reference-count":13,"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":[[2018,2]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>A poor response to erythropoiesis-stimulating agents such as darbepoetin alfa has been associated with adverse outcomes in patients with diabetes mellitus, chronic kidney disease, and anemia; whether this is also true in heart failure is unclear.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results:<\/jats:title>\n            <jats:p>We performed a post hoc analysis of the RED-HF trial (Reduction of Events by Darbepoetin Alfa in Heart Failure), in which 1008 patients with systolic heart failure and anemia (hemoglobin level, 9.0\u201312.0 g\/dL) were randomized to darbepoetin alfa. We examined the relationship between the hematopoietic response to darbepoetin alfa and the incidence of all-cause death or first heart failure hospitalization during a follow-up of 28 months. For the purposes of the present study, patients in the lowest quartile of hemoglobin change after 4 weeks were considered nonresponders. The median initial hemoglobin change in nonresponders (n=252) was \u22120.25 g\/dL and +1.00 g\/dL in the remainder of patients (n=756). Worse renal function, lower sodium levels, and less use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers were independently associated with nonresponse. Although a low endogenous erythropoietin level helped to differentiate responders from nonresponders, its predictive value in a multivariable model was poor (C statistic=0.69). Nonresponders had a higher rate of all-cause death or first heart failure hospitalization (hazard ratio, 1.25; 95% confidence interval, 1.02\u20131.54) and a higher risk of all-cause mortality (hazard ratio, 1.30; 95% confidence interval, 1.04\u20131.63) than responders.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>A poor response to darbepoetin alfa was associated with worse outcomes in heart failure patients with anemia. Patients with a poor response were difficult to identify using clinical and biochemical biomarkers.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Clinical Trial 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: NCT00358215.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circheartfailure.117.004431","type":"journal-article","created":{"date-parts":[[2018,1,25]],"date-time":"2018-01-25T01:10:15Z","timestamp":1516842615000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":16,"title":["Hyporesponsiveness to Darbepoetin Alfa in Patients With Heart Failure and Anemia in the RED-HF Study (Reduction of Events by Darbepoetin Alfa in Heart Failure)"],"prefix":"10.1161","volume":"11","author":[{"given":"Peter","family":"van der Meer","sequence":"first","affiliation":[{"name":"From the Department of Cardiology, University Medical Center Groningen, University of Groningen, the Netherlands (P.v.d.M., N.G.B., B.D.W., D.J.v.V.); Cardiovascular Division, Brigham and Women\u2019s Hospital, Boston, MA (M.A.P., S.D.S.), Amgen, Thousand Oaks, CA (K.O.); Department of Medicine, University of Minnesota Medical School and VA Medical Center, Minneapolis (I.S.A.); BHF Cardiovascular Research Centre, University of Glasgow, United Kingdom (J.J.V.M.); Department of Medicine, Sahlgrenska..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niels","family":"Grote Beverborg","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, University Medical Center Groningen, University of Groningen, the Netherlands (P.v.d.M., N.G.B., B.D.W., D.J.v.V.); Cardiovascular Division, Brigham and Women\u2019s Hospital, Boston, MA (M.A.P., S.D.S.), Amgen, Thousand Oaks, CA (K.O.); Department of Medicine, University of Minnesota Medical School and VA Medical Center, Minneapolis (I.S.A.); BHF Cardiovascular Research Centre, University of Glasgow, United Kingdom (J.J.V.M.); Department of Medicine, Sahlgrenska..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc A.","family":"Pfeffer","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, University Medical Center Groningen, University of Groningen, the Netherlands (P.v.d.M., N.G.B., B.D.W., D.J.v.V.); Cardiovascular Division, Brigham and Women\u2019s Hospital, Boston, MA (M.A.P., S.D.S.), Amgen, Thousand Oaks, CA (K.O.); Department of Medicine, University of Minnesota Medical School and VA Medical Center, Minneapolis (I.S.A.); BHF Cardiovascular Research Centre, University of Glasgow, United Kingdom (J.J.V.M.); Department of Medicine, Sahlgrenska..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kurt","family":"Olson","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, University Medical Center Groningen, University of Groningen, the Netherlands (P.v.d.M., N.G.B., B.D.W., D.J.v.V.); Cardiovascular Division, Brigham and Women\u2019s Hospital, Boston, MA (M.A.P., S.D.S.), Amgen, Thousand Oaks, CA (K.O.); Department of Medicine, University of Minnesota Medical School and VA Medical Center, Minneapolis (I.S.A.); BHF Cardiovascular Research Centre, University of Glasgow, United Kingdom (J.J.V.M.); Department of Medicine, Sahlgrenska..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inder S.","family":"Anand","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, University Medical Center Groningen, University of Groningen, the Netherlands (P.v.d.M., N.G.B., B.D.W., D.J.v.V.); Cardiovascular Division, Brigham and Women\u2019s Hospital, Boston, MA (M.A.P., S.D.S.), Amgen, Thousand Oaks, CA (K.O.); Department of Medicine, University of Minnesota Medical School and VA Medical Center, Minneapolis (I.S.A.); BHF Cardiovascular Research Centre, University of Glasgow, United Kingdom (J.J.V.M.); Department of Medicine, Sahlgrenska..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B. Daan","family":"Westenbrink","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, University Medical Center Groningen, University of Groningen, the Netherlands (P.v.d.M., N.G.B., B.D.W., D.J.v.V.); Cardiovascular Division, Brigham and Women\u2019s Hospital, Boston, MA (M.A.P., S.D.S.), Amgen, Thousand Oaks, CA (K.O.); Department of Medicine, University of Minnesota Medical School and VA Medical Center, Minneapolis (I.S.A.); BHF Cardiovascular Research Centre, University of Glasgow, United Kingdom (J.J.V.M.); Department of Medicine, Sahlgrenska..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John J.V.","family":"McMurray","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, University Medical Center Groningen, University of Groningen, the Netherlands (P.v.d.M., N.G.B., B.D.W., D.J.v.V.); Cardiovascular Division, Brigham and Women\u2019s Hospital, Boston, MA (M.A.P., S.D.S.), Amgen, Thousand Oaks, CA (K.O.); Department of Medicine, University of Minnesota Medical School and VA Medical Center, Minneapolis (I.S.A.); BHF Cardiovascular Research Centre, University of Glasgow, United Kingdom (J.J.V.M.); Department of Medicine, Sahlgrenska..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl","family":"Swedberg","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, University Medical Center Groningen, University of Groningen, the Netherlands (P.v.d.M., N.G.B., B.D.W., D.J.v.V.); Cardiovascular Division, Brigham and Women\u2019s Hospital, Boston, MA (M.A.P., S.D.S.), Amgen, Thousand Oaks, CA (K.O.); Department of Medicine, University of Minnesota Medical School and VA Medical Center, Minneapolis (I.S.A.); BHF Cardiovascular Research Centre, University of Glasgow, United Kingdom (J.J.V.M.); Department of Medicine, Sahlgrenska..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James B.","family":"Young","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, University Medical Center Groningen, University of Groningen, the Netherlands (P.v.d.M., N.G.B., B.D.W., D.J.v.V.); Cardiovascular Division, Brigham and Women\u2019s Hospital, Boston, MA (M.A.P., S.D.S.), Amgen, Thousand Oaks, CA (K.O.); Department of Medicine, University of Minnesota Medical School and VA Medical Center, Minneapolis (I.S.A.); BHF Cardiovascular Research Centre, University of Glasgow, United Kingdom (J.J.V.M.); Department of Medicine, Sahlgrenska..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott D.","family":"Solomon","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, University Medical Center Groningen, University of Groningen, the Netherlands (P.v.d.M., N.G.B., B.D.W., D.J.v.V.); Cardiovascular Division, Brigham and Women\u2019s Hospital, Boston, MA (M.A.P., S.D.S.), Amgen, Thousand Oaks, CA (K.O.); Department of Medicine, University of Minnesota Medical School and VA Medical Center, Minneapolis (I.S.A.); BHF Cardiovascular Research Centre, University of Glasgow, United Kingdom (J.J.V.M.); Department of Medicine, Sahlgrenska..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dirk J.","family":"van Veldhuisen","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, University Medical Center Groningen, University of Groningen, the Netherlands (P.v.d.M., N.G.B., B.D.W., D.J.v.V.); Cardiovascular Division, Brigham and Women\u2019s Hospital, Boston, MA (M.A.P., S.D.S.), Amgen, Thousand Oaks, CA (K.O.); Department of Medicine, University of Minnesota Medical School and VA Medical Center, Minneapolis (I.S.A.); BHF Cardiovascular Research Centre, University of Glasgow, United Kingdom (J.J.V.M.); Department of Medicine, Sahlgrenska..."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000134279.79571.73"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2011.77"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ehj.2003.11.017"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1214865"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehw128"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0907845"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1005109"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2004.03.052"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.844662"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehl419"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfp098"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1797.2007.00810.x"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hft120"}],"container-title":["Circulation: Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCHEARTFAILURE.117.004431","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T01:14:31Z","timestamp":1715562871000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCHEARTFAILURE.117.004431"}},"subtitle":["Clinical and Prognostic Associations"],"short-title":[],"issued":{"date-parts":[[2018,2]]},"references-count":13,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2018,2]]}},"alternative-id":["10.1161\/CIRCHEARTFAILURE.117.004431"],"URL":"https:\/\/doi.org\/10.1161\/circheartfailure.117.004431","relation":{},"ISSN":["1941-3289","1941-3297"],"issn-type":[{"value":"1941-3289","type":"print"},{"value":"1941-3297","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,2]]},"assertion":[{"value":"2017-04-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-11-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-01-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e004431"}}