{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T19:16:01Z","timestamp":1782846961097,"version":"3.54.5"},"reference-count":16,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T00:00:00Z","timestamp":1624233600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Heart Fail"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Sacubitril\/valsartan improves morbidity and mortality in patients with heart failure and reduced ejection fraction (HFrEF). Whether initiation of sacubitril\/valsartan limits the use and dosing of other elements of guideline\u2010directed medical therapy for HFrEF is unknown. We examined the effects of sacubitril\/valsartan, compared with enalapril, on \u03b2\u2010blocker and mineralocorticoid receptor antagonist (MRA) use and dosing in a large randomized clinical trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      Patients with full data on medication use were included. We examined \u03b2\u2010blocker and MRA use in patients randomized to sacubitril\/valsartan vs. enalapril through 12\u2010month follow\u2010up. New initiations and discontinuations of \u03b2\u2010blocker and MRA were compared between treatment groups. Overall, 8398 (99.9%) had full medication and dose data at baseline. Baseline use of \u03b2\u2010blocker and MRA at any dose was 87% and 56%, respectively. Mean doses of \u03b2\u2010blocker and MRA were similar between treatment groups at baseline and at 6\u2010month and 12\u2010month follow\u2010up. New initiations through 12\u2010month follow\u2010up were infrequent and similar in the sacubitril\/valsartan and enalapril groups for \u03b2\u2010blockers [37 (9.0%) vs. 42 (10.2%),\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.56] and MRA [127 (7.6%) vs. 143 (9.2%),\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.10]. Among patients on MRA therapy at baseline, there were fewer MRA discontinuations in patients on sacubitril\/valsartan as compared with enalapril at 12\u2009months [125 (6.2%) vs. 187 (9.0%),\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.001]. Discontinuations of \u03b2\u2010blockers were not significantly different between groups in follow\u2010up (2.2% vs. 2.6%,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.26).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Initiation of sacubitril\/valsartan, even when titrated to target dose, did not appear to lead to greater discontinuation or dose down\u2010titration of other key guideline\u2010directed medical therapies, and was associated with fewer discontinuations of MRA. Use of sacubitril\/valsartan (when compared with enalapril) may promote sustained MRA use in follow\u2010up.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.2259","type":"journal-article","created":{"date-parts":[[2021,6,8]],"date-time":"2021-06-08T18:24:55Z","timestamp":1623176695000},"page":"1518-1524","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Effect of sacubitril\/valsartan vs. enalapril on changes in heart failure therapies over time: the\n                    <scp>PARADIGM\u2010HF<\/scp>\n                    trial"],"prefix":"10.1093","volume":"23","author":[{"given":"Ankeet S.","family":"Bhatt","sequence":"first","affiliation":[{"name":"Division of Cardiology Brigham and Women's Hospital  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muthiah","family":"Vaduganathan","sequence":"additional","affiliation":[{"name":"Division of Cardiology Brigham and Women's Hospital  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian L.","family":"Claggett","sequence":"additional","affiliation":[{"name":"Division of Cardiology Brigham and Women's Hospital  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiankang","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Cardiology Brigham and Women's Hospital  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milton","family":"Packer","sequence":"additional","affiliation":[{"name":"Baylor Heart and Vascular Institute, Baylor University Medical Center  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akshay S.","family":"Desai","sequence":"additional","affiliation":[{"name":"Division of Cardiology Brigham and Women's Hospital  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin P.","family":"Lefkowitz","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation  East Hanover NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean L.","family":"Rouleau","sequence":"additional","affiliation":[{"name":"Montreal Heart Institute, Universit\u00e9 de Montr\u00e9al  Montr\u00e9al QC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor C.","family":"Shi","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation  East Hanover NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Zile","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina, Charleston and Ralph H. Johnston Veterans Administration Medical Center  Charleston SC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Swedberg","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Medicine University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orly","family":"Vardeny","sequence":"additional","affiliation":[{"name":"Center for Care Delivery and Outcomes Research, Minneapolis VA Health Care System, and University of Minnesota  Minneapolis MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.V.","family":"McMurray","sequence":"additional","affiliation":[{"name":"British Heart Foundation Cardiovascular Research Centre, University of Glasgow  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott D.","family":"Solomon","sequence":"additional","affiliation":[{"name":"Division of Cardiology Brigham and Women's Hospital  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,6,21]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000509"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.592"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.04.070"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1409077"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.117.004745"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.116.003212"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2016.4733"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hft052"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.1402"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30748-0"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2018.02.004"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2020.11.009"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2021.01.044"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.114.013748"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2020.08.017"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2020.11.022"}],"container-title":["European Journal of Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ejhf.2259","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ejhf.2259","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ejhf.2259","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T12:14:58Z","timestamp":1767701698000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ejhf.2259"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,21]]},"references-count":16,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2021,9]]}},"alternative-id":["10.1002\/ejhf.2259"],"URL":"https:\/\/doi.org\/10.1002\/ejhf.2259","archive":["Portico"],"relation":{},"ISSN":["1388-9842","1879-0844"],"issn-type":[{"value":"1388-9842","type":"print"},{"value":"1879-0844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,21]]},"assertion":[{"value":"2021-03-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}