{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T04:01:55Z","timestamp":1792123315528,"version":"4.4.0"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T00:00:00Z","timestamp":1669680000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T00:00:00Z","timestamp":1669680000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Novartis Sweden AB."},{"DOI":"10.13039\/501100005760","name":"University of Gothenburg","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005760","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Res Cardiol"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Aims<\/jats:title>\n                <jats:p>Sacubitril\/valsartan is a first-in-class angiotensin receptor\u2013neprilysin inhibitor (ARNI) with a class-1 guideline recommendation. We assessed the real-world effectiveness of ARNI versus angiotensin-converting enzyme inhibitor\/angiotensin receptor blocker (ACEi\/ARB) on all-cause and cardiovascular (CV)-related mortality and hospitalizations in heart failure (HF) with reduced or mildly reduced ejection fraction (EF).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Patient-level clinical, laboratory, drug dispensation, hospitalization, and mortality data were derived from the Swedish Heart Failure Registry (SwedeHF) and interlinked databases (1 April 2016\u201331 December 2020). Eligible ARNI:ACEi\/ARB patients (<jats:italic>n<\/jats:italic>\u2009=\u20097275:24,604) had a left ventricular EF\u2009&lt;\u200950%. Mortality and hospitalizations with ARNI (\u2264\u20093\u00a0months pre-\/post-1 April 2016 index [SwedeHF]; <jats:italic>n<\/jats:italic>\u2009=\u20091506) versus ACEi\/ARB (\u2264\u20093\u00a0months post-index; <jats:italic>n<\/jats:italic>\u2009=\u200917,108) were assessed using propensity score matching (1:1 ratio) with clinical variables, and sensitivity analysis (1:2\/1:3 with, and 1:2 without clinical variables).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>ARNI induced a 23% reduction in all-cause mortality versus ACEi\/ARB (1:1 hazard ratio [HR; 95% confidence interval\u00a0(CI)]: 0.77 [0.63\u20130.95], <jats:italic>p<\/jats:italic>\u2009=\u20090.013), and a non-significant 23% relative risk reduction in CV-related mortality (0.77 [0.54\u20131.09], <jats:italic>p<\/jats:italic>\u2009=\u20090.13), but no difference in all-cause or CV-related hospitalization (1.02 [0.91\u20131.13]; <jats:italic>p<\/jats:italic>\u2009=\u20090.76; 1.01 [0.91\u20131.15]; <jats:italic>p<\/jats:italic>\u2009=\u20090.84, respectively). Sensitivity analyses confirmed all-cause mortality was reduced for ARNI versus ACEi\/ARB (HR\u00a00.90 [95% CI 0.82\u20130.99], <jats:italic>p<\/jats:italic>\u2009=\u20090.026), but not CV-related mortality (HR\u00a01.04 [95% CI 0.89\u20131.22], <jats:italic>p<\/jats:italic>\u2009=\u20090.63).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>In this nationwide real-world study including a population of patients with HF with reduced or mildly reduced EF, ARNI as part of guideline-led Swedish clinical practice was associated with a statistically significant relative risk reduction in all-cause mortality compared with ACEi\/ARB.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00392-022-02124-w","type":"journal-article","created":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T07:22:37Z","timestamp":1669706557000},"page":"167-174","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Real-world comparative effectiveness of ARNI versus ACEi\/ARB in HF with reduced or mildly reduced ejection fraction"],"prefix":"10.1007","volume":"112","author":[{"given":"Michael","family":"Fu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aldina","family":"Pivodic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oskar","family":"K\u00e4ck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madlaina","family":"Costa-Scharplatz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf","family":"Dahlstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars H.","family":"Lund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,11,29]]},"reference":[{"key":"2124_CR1","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1056\/NEJMoa1409077","volume":"371","author":"JJV McMurray","year":"2014","unstructured":"McMurray JJV, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR (2014) Angiotensin\u2013neprilysin inhibition versus enalapril in heart failure. N Engl J Med 371:993\u20131004. https:\/\/doi.org\/10.1056\/NEJMoa1409077","journal-title":"N Engl J Med"},{"key":"2124_CR2","doi-asserted-by":"publisher","first-page":"1609","DOI":"10.1056\/NEJMoa1908655","volume":"381","author":"SD Solomon","year":"2019","unstructured":"Solomon SD, McMurray JJV, Anand IS, Ge J, Lam CSP, Maggioni AP, Martinez F, Packer M, Pfeffer MA, Pieske B, Redfield MM, Rouleau JL, van Veldhuisen DJ, Zannad F, Zile MR, Desai AS, Claggett B, Jhund PS, Boytsov SA, Comin-Colet J, Cleland J, D\u00fcngen H-D, Goncalvesova E, Katova T, Kerr Saraiva JF, Lelonek M, Merkely B, Senni M, Shah SJ, Zhou J, Rizkala AR, Gong J, Shi VC, Lefkowitz MP (2019) Angiotensin\u2013neprilysin inhibition in heart failure with preserved ejection fraction. 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AP has nothing related or unrelated to the present work. OK and MC\u2010S are employees of Novartis. OK was the Novartis study lead, which included project management, facilitation, and support with heart failure-specific scientific contribution to the protocol as well as development of the statistical analysis plan and manuscript. MC-S. was the Novartis Real World Evidence (RWE) lead, contributing scientific expertise in RWE study design during protocol development as well as finalization of the statistical analysis plan and manuscript development. UD has received grants from AstraZeneca, Boston Scientific, Boehringer Ingelheim, Pfizer, Roche Diagnostics and Vifor Pharma, and personal fees from Amgen, AstraZeneca, Pfizer and Novartis. All unrelated to the present manuscript. LHL has received personal fees from Abbott, Bayer, Medscape, Merck, Myokardia, Pharmacosmos, and Sanofi; grants and personal fees from AstraZeneca, Boehringer Ingelheim, Mundipharma, Novartis, Relypsa, and Vifor-Fresenius; grants from Boston Scientific.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This study was conducted in accordance with the Guidelines for Good Pharmacoepidemiology Practices, followed the ethical principles laid down in the Declaration of Helsinki, fulfilled the criteria of a European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) study, and was in accordance with the ENCePP Code of Conduct. The study had ethics approval (permission number: DNR 2020-03988) and no identifiable personal information of the participants in this retrospective observational study will be provided to any outside entity. All registers except SwedeHF are administrative and do not require patient consent. SwedeHF is a quality register and does not require consent, but patients are informed of entry into national quality registers and allowed to opt out. This publication was developed in line with STROBE guidelines, summarized in the Supporting Information, Table S5<i>.<\/i>","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}}]}}