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Here, we report the results of a pre-specified analysis that separately evaluates these patients stratified by LVEF: preserved (\u2265\u200950%) (<jats:italic>n<\/jats:italic>\u2009=\u20094,005; 66.9%) or mid-range (41\u201349%). In patients with LVEF \u2009\u2265\u200950%, empagliflozin reduced the risk of cardiovascular death or HHF (the primary endpoint) by 17% versus placebo (hazard ratio (HR) 0.83; 95% confidence interval (CI): 0.71\u20130.98, <jats:italic>P<\/jats:italic>\u2009=\u20090.024). For the key secondary endpoint, the HR for total HHF was 0.83 (95%CI: 0.66\u20131.04, <jats:italic>P<\/jats:italic>\u2009=\u20090.11). For patients with an LVEF of 41\u201349%, the HR for empagliflozin versus placebo was 0.71 (95%CI: 0.57\u20130.88, <jats:italic>P<\/jats:italic>\u2009=\u20090.002) for the primary outcome (<jats:italic>P<\/jats:italic><jats:sub>interaction<\/jats:sub>\u2009=\u20090.27), and 0.57 (95%CI: 0.42\u20130.79, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) for total HHF (<jats:italic>P<\/jats:italic><jats:sub>interaction<\/jats:sub>\u2009=\u20090.06). These results, together with those from the EMPEROR-Reduced trial in patients with LVEF\u2009&lt;\u200940%, support the use of empagliflozin across the full spectrum of LVEF in heart failure.<\/jats:p>","DOI":"10.1038\/s41591-022-02041-5","type":"journal-article","created":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T17:03:08Z","timestamp":1670259788000},"page":"2512-2520","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Efficacy of empagliflozin in heart failure with preserved versus mid-range ejection fraction: a pre-specified analysis of EMPEROR-Preserved"],"prefix":"10.1038","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0805-8683","authenticated-orcid":false,"given":"Stefan D.","family":"Anker","sequence":"first","affiliation":[]},{"given":"Javed","family":"Butler","sequence":"additional","affiliation":[]},{"given":"Muhammad Shariq","family":"Usman","sequence":"additional","affiliation":[]},{"given":"Gerasimos","family":"Filippatos","sequence":"additional","affiliation":[]},{"given":"Jo\u00e3o Pedro","family":"Ferreira","sequence":"additional","affiliation":[]},{"given":"Edimar","family":"Bocchi","sequence":"additional","affiliation":[]},{"given":"Michael","family":"B\u00f6hm","sequence":"additional","affiliation":[]},{"given":"Hans Pieter Brunner-La","family":"Rocca","sequence":"additional","affiliation":[]},{"given":"Dong-Ju","family":"Choi","sequence":"additional","affiliation":[]},{"given":"Vijay","family":"Chopra","sequence":"additional","affiliation":[]},{"given":"Eduardo","family":"Chuquiure","sequence":"additional","affiliation":[]},{"given":"Nadia","family":"Giannetti","sequence":"additional","affiliation":[]},{"given":"Juan Esteban","family":"Gomez-Mesa","sequence":"additional","affiliation":[]},{"given":"Stefan","family":"Janssens","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8338-1798","authenticated-orcid":false,"given":"James L.","family":"Januzzi","sequence":"additional","affiliation":[]},{"given":"Jos\u00e9 R.","family":"Gonz\u00e1lez-Juanatey","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6514-0723","authenticated-orcid":false,"given":"Bela","family":"Merkely","sequence":"additional","affiliation":[]},{"given":"Stephen J.","family":"Nicholls","sequence":"additional","affiliation":[]},{"given":"Sergio V.","family":"Perrone","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4986-7129","authenticated-orcid":false,"given":"Ileana L.","family":"Pi\u00f1a","sequence":"additional","affiliation":[]},{"given":"Piotr","family":"Ponikowski","sequence":"additional","affiliation":[]},{"given":"Michele","family":"Senni","sequence":"additional","affiliation":[]},{"given":"David","family":"Sim","sequence":"additional","affiliation":[]},{"given":"Jindrich","family":"Spinar","sequence":"additional","affiliation":[]},{"given":"Iain","family":"Squire","sequence":"additional","affiliation":[]},{"given":"Stefano","family":"Taddei","sequence":"additional","affiliation":[]},{"given":"Hiroyuki","family":"Tsutsui","sequence":"additional","affiliation":[]},{"given":"Subodh","family":"Verma","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9054-8779","authenticated-orcid":false,"given":"Dragos","family":"Vinereanu","sequence":"additional","affiliation":[]},{"given":"Jian","family":"Zhang","sequence":"additional","affiliation":[]},{"given":"Tomoko","family":"Iwata","sequence":"additional","affiliation":[]},{"given":"Janet M.","family":"Schnee","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1215-0746","authenticated-orcid":false,"given":"Martina","family":"Brueckmann","sequence":"additional","affiliation":[]},{"given":"Stuart J.","family":"Pocock","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7456-1570","authenticated-orcid":false,"given":"Faiez","family":"Zannad","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2022,12,5]]},"reference":[{"key":"2041_CR1","doi-asserted-by":"publisher","first-page":"1668","DOI":"10.1016\/j.jacc.2015.03.043","volume":"65","author":"JP Kelly","year":"2015","unstructured":"Kelly, J. 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M.S.<\/b> reports consultancy fees from Abbot, Bayer, Bayer Healthcare, Merck, Novartis and Vifor Pharma. <b>I.S.<\/b> reports research grants from Boehringer Ingelheim. <b>H.T.<\/b> reports personal fees from Boehringer Ingelheim, Astellas Pharma Inc., Pfizer Japan Inc., Bristol-Myers Squibb Company, Otsuka Pharmaceutical Co., Ltd, Daiichi Sankyo Co., Ltd, Kowa Pharmaceutical Co. Ltd and Teijin Pharma Ltd; grants from Actelion Pharmaceuticals Japan Ltd, Japan Tobacco Inc., Daiichi Sankyo Co., Ltd, IQVIA Services Japan, Omron Healthcare, Astellas Pharma Inc. and Teijin Pharma Ltd; grants and personal fees from Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Company Limited and MSD KK; and grants, personal fees and other from Nippon Boehringer Ingelheim Co., Ltd and Novartis Pharma K.K, outside the submitted work. <b>S.V.<\/b> reports research grants and honoraria from Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, HLS Therapeutics, Janssen, Novartis, NovoNordisk, PhaseBio and Pfizer; and honoraria from Sanofi, Sun Pharmaceuticals and the Toronto Knowledge Translation Working Group. He is a member of the scientific excellence committee of the EMPEROR-Reduced trial and served as a national lead investigator of the DAPA-HF and EMPEROR-Reduced trials. He is the President of the Canadian Medical and Surgical Knowledge Translation Research Group, a federally incorporated not-for-profit physician organization. <b>D.V.<\/b> reports consulting fees from AstraZeneca, Boehringer Ingelheim and Novartis Pharma. <b>T.I.<\/b>, <b>J.M.S.<\/b> and <b>M.Br.<\/b> are employees of Boehringer Ingelheim. <b>S.J.P.<\/b> reports personal fees from Boehringer Ingelheim during the conduct of the study. <b>F.Z.<\/b> reports personal fees from Boehringer Ingelheim during the conduct of the study; personal fees from Janssen, Novartis, Boston Scientific, Amgen, CVRx, AstraZeneca, Vifor Fresenius, Cardior, Cereno Pharmaceutical, Applied Therapeutics, Merck, Bayer and Cellprothera outside of the submitted work; and other support from cardiovascular clinical trialists and Cardiorenal, outside of the submitted work. All other authors have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}