{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:44:14Z","timestamp":1769129054153,"version":"3.49.0"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"content-version":"vor","delay-in-days":2371,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2019,7,24]],"date-time":"2019-07-24T00:00:00Z","timestamp":1563926400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Cyberonics Incorporated, Houston, TX, USA","award":["None"],"award-info":[{"award-number":["None"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Clinical trials of new heart failure (HF) therapies administer guideline-directed medical therapy (GDMT) as background pharmacologic treatment (BPT). In the ANTHEM-HF Pilot Study, addition of autonomic regulation therapy to GDMT significantly improved left ventricular function, New York Heart Association (NYHA) class, 6 min walk distance, and quality of life in patients with HF with reduced ejection fraction (HFrEF). A post hoc analysis was performed to compare BPT in ANTHEM-HF with two other trials of novel HF therapies: the PARADIGM-HF study of sacubitril\u2013valsartan and the SHIFT study of ivadrabine. All three studies evaluated patients with HFrEF, and the recommendations for use of GDMT were similar. A left ventricular ejection fraction \u226440% was required for entry into ANTHEM-HF and PARADIGM-HF and \u226435% for SHIFT. NYHA 2 or 3 symptoms were required for entry into ANTHEM-HF, and patients with predominantly NYHA 2 or 3 symptoms were enrolled in PARADIGM-HF and SHIFT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Data on BPT were obtained from peer-reviewed publications and the public domain. Pearson's \u03c72 test was used to evaluate differences in proportions, and Student's unpaired t-test was used to evaluate differences in mean values. The minimum period of stable GDMT required before randomization was longer in ANTHEM-HF: 3 months vs. 1 month in PARADIGM-HF and SHIFT, respectively. When compared with PARADIGM-HF and SHIFT, more patients in ANTHEM-HF received beta-blockers (100% vs. 93% and 89%, P &amp;lt; 0.04 and P &amp;lt; 0.007) and mineralocorticoid receptor antagonists (75% vs. 55% and 61%, P &amp;lt; 0.002 and P &amp;lt; 0.03). More patients in PARADIGM-HF received an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker than in ANTHEM-HF or SHIFT (100% vs. 85%, P &amp;lt; 0.0001, and 100% vs. 91%, P &amp;lt; 0.001), which was related to PARADIGM's design. When beta-blocker doses in ANTHEM-HF and SHIFT were compared, significantly fewer patients in ANTHEM-HF received doses \u2265100% of target (10% vs. 23%, P &amp;lt; 0.02), and fewer patients tended to receive doses \u226550% of target (17% vs. 26%, P = 0.11). When ANTHEM-HF and PARADIGM-HF were compared, more patients in ANTHEM-HF tended to receive doses \u2265100% of target (10% vs. 7%, P = 0.36), and fewer patients tended to receive doses \u226550% of target (17% vs. 20%, P = 0.56).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Background treatment with GDMT in ANTHEM-HF compared favourably with that in two other contemporary trials of new HF therapies. The minimum period of stable GDMT required before randomization was longer, and GDMT remained unchanged for the study's duration. These findings serve to further support the potential role of autonomic regulation therapy as an adjunct to GDMT for patients with HFrEF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.12484","type":"journal-article","created":{"date-parts":[[2019,7,24]],"date-time":"2019-07-24T09:44:48Z","timestamp":1563961488000},"page":"1052-1056","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Background Pharmacological Therapy in the ANTHEM-HF: Comparison to Contemporary Trials of Novel Heart Failure Therapies"],"prefix":"10.1093","volume":"6","author":[{"given":"Rajendra K.","family":"Premchand","sequence":"first","affiliation":[{"name":"Krishna Institute of Medical Sciences , Secunderabad ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamal","family":"Sharma","sequence":"additional","affiliation":[{"name":"Sanjivani Super Specialty Hospitals , Ahmedabad ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanjay","family":"Mittal","sequence":"additional","affiliation":[{"name":"Medanta, The Medicity , Gurugram, Haryana ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rufino","family":"Monteiro","sequence":"additional","affiliation":[{"name":"Vintage Hospital , Panaji, Goa ,","place":["India"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Imad","family":"Libbus","sequence":"additional","affiliation":[{"name":"LivaNova USA, Inc. , Houston, TX ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey L.","family":"Ardell","sequence":"additional","affiliation":[{"name":"University of California, Los Angeles , Los Angeles, CA ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas D.","family":"Gregory","sequence":"additional","affiliation":[{"name":"Clinical Cardiovascular Science Foundation , Boston, MA ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruce H.","family":"KenKnight","sequence":"additional","affiliation":[{"name":"LivaNova USA, Inc. , Houston, TX ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Badri","family":"Amurthur","sequence":"additional","affiliation":[{"name":"LivaNova USA, Inc. , Houston, TX ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenzo A.","family":"DiCarlo","sequence":"additional","affiliation":[{"name":"LivaNova USA, Inc. , Houston, TX ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inder S.","family":"Anand","sequence":"additional","affiliation":[{"name":"University of Minnesota (Emeritus) , Minneapolis, MN ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,7,24]]},"reference":[{"key":"2026012115085418200_ehf212484-bib-0001","doi-asserted-by":"crossref","first-page":"e137","DOI":"10.1161\/CIR.0000000000000509","article-title":"2017 ACC\/AHA\/HFSA focused update of the 2013 ACCF\/AHA guideline for the management of heart failure: a report of the American College of Cardiology\/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America","volume":"136","author":"Yancy","year":"2017","journal-title":"Circulation"},{"key":"2026012115085418200_ehf212484-bib-0002","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1093\/eurheartj\/ehw128","article-title":"2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). 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