{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:10:50Z","timestamp":1792181450489,"version":"4.4.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:00:00Z","timestamp":1787961600000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"German Federal Ministry of Research, Technology, and Space","award":["01KG1303"],"award-info":[{"award-number":["01KG1303"]}]},{"name":"German Federal Ministry of Research, Technology, and Space","award":["01KG1907"],"award-info":[{"award-number":["01KG1907"]}]},{"name":"Braukmann Wittenberg Heart Foundation"},{"DOI":"10.13039\/501100005971","name":"German Heart Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005971","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Digitoxin reduced the composite of death or worsening heart failure in DIGIT-HF, but whether these benefits translate into economic value remains unknown. We assessed its cost-effectiveness as add-on therapy for heart failure with reduced ejection fraction (HFrEF) across all 27 European Union Member States (EU-27) and the United States (US).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We developed a DIGIT-HF-informed, multi-jurisdictional three-state Markov cost-utility model projecting 10-year and lifetime outcomes. Clinical risks and intention-to-treat effects were held constant; hospitalization costs, EQ-5D-5L utilities, digitoxin costs, discounting, and willingness-to-pay (WTP) thresholds varied by jurisdiction. Uncertainty was assessed using 10 000 probabilistic simulations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Across the EU-27, digitoxin was cost-effective at 10 years, with incremental costs of \u2212\u20ac338 to +\u20ac25 per patient, incremental quality-adjusted life-years (QALYs) of 0.188\u20130.231, and a maximum incremental cost-effectiveness ratio (ICER) of \u20ac120\/QALY. Over lifetime, corresponding ranges were \u2212\u20ac79 to +\u20ac72, 0.373\u20130.453 QALYs, and a maximum ICER of \u20ac174\/QALY. At \u20ac50 000\/QALY, cost-effectiveness probability was 92%. Digitoxin was cost-saving in 24 of 27 Member States at 10 years and 10 of 27 over lifetime. In the USA, it was cost-saving (lifetime savings US$405 per patient; 0.43 QALYs; 93.4% probability of cost-effectiveness).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Digitoxin generated clinically meaningful health benefits at negligible incremental cost and remained cost-effective across every evaluated EU-27 healthcare system and the USA. Economic value emerged earliest within the first decade and in higher-cost hospital systems, while lifetime analysis captured larger cumulative gains in quality-adjusted survival.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ejhf\/xuag270","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T11:46:12Z","timestamp":1787139972000},"source":"Crossref","is-referenced-by-count":1,"title":["Cost-effectiveness of digitoxin in heart failure with reduced ejection fraction in the European Union and the United States"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0534-132X","authenticated-orcid":false,"given":"Priyanka","family":"Boettger","sequence":"first","affiliation":[{"name":"Department of Cardiology and Angiology, Justus-Liebig-University Giessen , Klinikstrasse 33, Giessen 35392 ,","place":["Germany"]},{"name":"London School of Economics and Political Science Department of Health Policy, , Houghton Street, London WC2A 2AE ,","place":["UK"]},{"name":"Cardio-Pulmonary Institute (CPI) , Justus Liebig University Giessen, Aulweg 130, 35392, Giessen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1455-2474","authenticated-orcid":false,"given":"Anika","family":"Gro\u00dfhennig","sequence":"additional","affiliation":[{"name":"Institute for Biostatistics, Hannover Medical School , Carl-Neuberg-Stra\u00dfe 1, 30625 Hannover ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"St\u00f6rk","sequence":"additional","affiliation":[{"name":"Department of Clinical Research and Epidemiology, Comprehensive Heart Failure Center, University Hospital W\u00fcrzburg , Am Schwarzenberg 15, 97078 W\u00fcrzburg ,","place":["Germany"]},{"name":"Department of Internal Medicine I, University Hospital W\u00fcrzburg , Oberd\u00fcrrbacher Stra\u00dfe 6, 97080 W\u00fcrzburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5710-3540","authenticated-orcid":false,"given":"Dominik","family":"Berliner","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg-Stra\u00dfe 1, 30625 Hannover ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Schwab","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Paracelsus Medical University \u00a0 Nuremberg, Klinikum N\u00fcrnberg, Breslauer Stra\u00dfe 201, 90471 Nuremberg ,","place":["Germany"]},{"name":"MVZ Kardiologie, Klinikum Neumarkt , Regensburger Stra\u00dfe 109, 92318 Neumarkt ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8944-1192","authenticated-orcid":false,"given":"Andreas","family":"Rieth","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Kerckhoff-Klinik, Benekestra\u00dfe 2\u20138, 61231 \u00a0 Bad Nauheim ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Maier","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, University Hospital Regensburg , Franz-Josef-Strau\u00df-Allee 11, 93053 Regensburg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Huelsmann","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna , W\u00e4hringer G\u00fcrtel 18\u201320, 1090 Vienna 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Medicine), Saarland University, Campus Universit\u00e4tsklinikum des Saarlandes , Kirrberger Stra\u00dfe 100, 66421 Homburg\/Saar ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1401-3219","authenticated-orcid":false,"given":"Armin","family":"Koch","sequence":"additional","affiliation":[{"name":"Institute for Biostatistics, Hannover Medical School , Carl-Neuberg-Stra\u00dfe 1, 30625 Hannover ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Sossalla","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology, Justus-Liebig-University Giessen , Klinikstrasse 33, Giessen 35392 ,","place":["Germany"]},{"name":"Cardio-Pulmonary Institute (CPI) , Justus Liebig University Giessen, Aulweg 130, 35392, Giessen ,","place":["Germany"]},{"name":"Department of Cardiology, Kerckhoff-Klinik, Benekestra\u00dfe 2\u20138, 61231 \u00a0 Bad Nauheim ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9341-117X","authenticated-orcid":false,"given":"Johann","family":"Bauersachs","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg-Stra\u00dfe 1, 30625 Hannover ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3911-2571","authenticated-orcid":false,"given":"Udo","family":"Bavendiek","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Angiology, Hannover Medical School, Carl-Neuberg-Stra\u00dfe 1, 30625 Hannover 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