{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T20:02:25Z","timestamp":1769112145489,"version":"3.49.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000},"content-version":"vor","delay-in-days":2175,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2020,1,5]],"date-time":"2020-01-05T00:00:00Z","timestamp":1578182400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>In the PARADIGM-heart failure trial, sacubitril-valsartan demonstrated a reduction in heart failure admissions and reduced all-cause mortality in patients with heart failure with reduced ejection fraction. Although real world data have shown similar benefits regarding efficacy and safety, there has been difficulty in achieving the target dose (TD). The factors preventing the achievement of TD remains unclear.<\/jats:p>\n                    <jats:p>This study assesses the tolerability, ability to achieve, and factors linked to attaining TD in a routine clinical population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>This is a retrospective single-centre review of patients switched from angiotensin-converting enzyme inhibitors\/angiotensin receptor blockers to sacubitril-valsartan between May 2016 and August 2018. Baseline and follow-up clinical characteristics and biomarker profiles were collected. Univariate and multivariate analyses were used to analyse predictors of achieving TD. Clinical response to sacubitril-valsartan was defined as a reduction in N terminal pro BNP of \u226530%, or an increase in left ventricular ejection fraction of \u22655% compared with baseline values.<\/jats:p>\n                    <jats:p>To date, a total of 322 patients (75% male patients) have been switched to sacubitril-valsartan. Those still in the titration phase were excluded (n = 25). Sacubitril-valsartan was not tolerated in 40 patients (12.4%). Those intolerant were older (73.4 years [68.3, 80.6] vs. 69.1 years [61.2, 76]; P = 0.003) and had worse renal function with estimated glomerular filtration rate (53.5 mL\/min\/1.72 m2 [36.8, 60.2] vs 60 mL\/min\/1.72 m2 [47, 77]; P \u2264 0.001). Of the remaining 257 patients, TD (97\/103 mg BD) was achieved in 194 patients (75.5%), while 37 patients (11.4%) were maintained on 49\/51 mg BD and 26 patients (8.1%) remained on 24\/26 mg BD. Symptomatic hypotension (74.6%) was the main impediment to attaining TD, followed by renal deterioration (12.7%), and to a lesser extent hyperkalaemia and gastrointestinal symptoms (4.8% each). Diuretic dose decrease was achieved in 37.2% of patients, and this was the strongest independent predictor of achieving TD (odds ratio = 2.1; 95% confidence interval [1.16, 3.8]; P = 0.014). Responder status by N terminal pro BNP criterion was observed in 99 of 214 patients (46.3%) while 70 of 142 (49.3%) attained the left ventricular ejection fraction response status. Achieving this response was independently linked to achieving TD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Sacubitril-valsartan was well tolerated. Achievement of TD was possible in the majority of the cohort and was linked to response metrics. Reduction in diuretic was required in a large percentage of the population and was the strongest predictor of attaining TD. Therefore, careful clinical attention to volume status assessment is essential to maximising the benefits of sacubitril-valsartan.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.12547","type":"journal-article","created":{"date-parts":[[2020,1,6]],"date-time":"2020-01-06T02:48:38Z","timestamp":1578278918000},"page":"159-167","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Sacubitril-Valsartan in a Routine Community Population: Attention to Volume Status Critical to Achieving Target Dose"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5504-2978","authenticated-orcid":false,"given":"Rebabonye B.","family":"Pharithi","sequence":"first","affiliation":[{"name":"Heart Failure Unit, St. Vincent University Hospital Health Care Group , Elm Park, Dublin, DO4 T6F4 ,","place":["Ireland"]},{"name":"University College Dublin , Belfield, Dublin ,","place":["Ireland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Ferre-Vallverdu","sequence":"additional","affiliation":[{"name":"Heart Failure Unit, St. Vincent University Hospital Health Care Group , Elm Park, Dublin, DO4 T6F4 ,","place":["Ireland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan S.","family":"Maisel","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Coronary Care Unit and Heart Failure Programme, Veterans Affairs San Diego Healthcare System, University of San Diego , San Diego , , CA","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eoin","family":"O'Connell","sequence":"additional","affiliation":[{"name":"Heart Failure Unit, St. Vincent University Hospital Health Care Group , Elm Park, Dublin, DO4 T6F4 ,","place":["Ireland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myra","family":"Walshe","sequence":"additional","affiliation":[{"name":"Heart Failure Unit, St. Vincent University Hospital Health Care Group , Elm Park, Dublin, DO4 T6F4 ,","place":["Ireland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claire","family":"Sweeney","sequence":"additional","affiliation":[{"name":"Heart Failure Unit, St. Vincent University Hospital Health Care Group , Elm Park, Dublin, DO4 T6F4 ,","place":["Ireland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Barton","sequence":"additional","affiliation":[{"name":"Heart Failure Unit, St. Vincent University Hospital Health Care Group , Elm Park, Dublin, DO4 T6F4 ,","place":["Ireland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathrine","family":"McDonald","sequence":"additional","affiliation":[{"name":"University College Dublin , Belfield, Dublin ,","place":["Ireland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"O'Hare","sequence":"additional","affiliation":[{"name":"Heart Failure Unit, St. Vincent University Hospital Health Care Group , Elm Park, Dublin, DO4 T6F4 ,","place":["Ireland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris","family":"Watson","sequence":"additional","affiliation":[{"name":"University College Dublin , Belfield, Dublin ,","place":["Ireland"]},{"name":"Centre for Experimental Medicine, Queen's University Belfast \u00a0","place":["Northern Ireland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joe","family":"Gallagher","sequence":"additional","affiliation":[{"name":"Heart Failure Unit, St. Vincent University Hospital Health Care Group , Elm Park, Dublin, DO4 T6F4 ,","place":["Ireland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Ledwidge","sequence":"additional","affiliation":[{"name":"Heart Failure Unit, St. Vincent University Hospital Health Care Group , Elm Park, Dublin, DO4 T6F4 ,","place":["Ireland"]},{"name":"University College Dublin , Belfield, Dublin ,","place":["Ireland"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth","family":"McDonald","sequence":"additional","affiliation":[{"name":"Heart Failure Unit, St. Vincent University Hospital Health Care Group , Elm Park, Dublin, DO4 T6F4 ,","place":["Ireland"]},{"name":"University College Dublin , Belfield, Dublin ,","place":["Ireland"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,1,5]]},"reference":[{"key":"2026012115053877200_ehf212547-bib-0001","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1056\/NEJMoa1409077","article-title":"Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure","volume":"371","author":"McMurray","year":"2014","journal-title":"N Engl J Med"},{"key":"2026012115053877200_ehf212547-bib-0002","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1161\/CIRCHEARTFAILURE.114.001785","article-title":"Angiotensin receptor neprilysin inhibitor LCZ696 attenuates cardiac remodeling and dysfunction after myocardial infarction by reducing cardiac fibrosis and hypertrophy;clinical perspective","volume":"8","author":"von Lueder","year":"2015","journal-title":"Circ Heart Fail"},{"key":"2026012115053877200_ehf212547-bib-0003","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1001\/jamacardio.2018.0398","article-title":"Effects of sacubitril\/valsartan on physical and social activity limitations in patients with heart failure: a secondary analysis of the PARADIGM-HF trial","volume":"3","author":"Chandra","year":"2018","journal-title":"JAMA Cardiol"},{"key":"2026012115053877200_ehf212547-bib-0004","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1056\/NEJMoa1812851","article-title":"Angiotensin-neprilysin inhibition in acute decompensated heart failure","volume":"380","author":"Velazquez","year":"2019","journal-title":"N Engl J Med"},{"key":"2026012115053877200_ehf212547-bib-0005","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1002\/ejhf.592","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). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC","volume":"18","author":"Ponikowski","year":"2016","journal-title":"Eur J Heart Fail"},{"key":"2026012115053877200_ehf212547-bib-0006","doi-asserted-by":"crossref","DOI":"10.1161\/CIR.0000000000000503","article-title":"2017 AHA\/ACC focused update of the 2014 AHA\/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology\/American Heart Association Task Force on Clinical Practice Guidelines","volume":"135","author":"Nishimura","year":"2017","journal-title":"Circulation"},{"key":"2026012115053877200_ehf212547-bib-0007","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1007\/s12471-018-1103-7","article-title":"Real-world heart failure management in 10,910 patients with chronic heart failure in the Netherlands","volume":"26","author":"Brugts","year":"2018","journal-title":"Netherlands Heart J"},{"key":"2026012115053877200_ehf212547-bib-0008","doi-asserted-by":"crossref","first-page":"2576","DOI":"10.1093\/eurheartj\/ehv330","article-title":"Efficacy and safety of LCZ696 (sacubitril-valsartan) according to age: insights from PARADIGM-HF","volume":"36","author":"Jhund","year":"2015","journal-title":"Eur Heart J"},{"key":"2026012115053877200_ehf212547-bib-0009","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1002\/ejhf.788","article-title":"What proportion of patients with chronic heart failure are eligible for sacubitril\u2013valsartan?","volume":"19","author":"Pellicori","year":"2017","journal-title":"Eur J Heart Fail"},{"key":"2026012115053877200_ehf212547-bib-0010","first-page":"1","article-title":"Sacubitril\/valsartan for heart failure with reduced left ventricular ejection fraction: a retrospective cohort study","volume":"19","author":"De Vecchis","year":"2018","journal-title":"Herz"},{"key":"2026012115053877200_ehf212547-bib-0011","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1080\/00015385.2018.1473825","article-title":"Impact of sacubitril\/valsartan on heart failure admissions: insights from real-world patient prescriptions","volume":"74","author":"Martens","year":"2018","journal-title":"Acta Cardiol"},{"key":"2026012115053877200_ehf212547-bib-0012","first-page":"1","article-title":"Effects of sacubitril\/valsartan on functional status and exercise capacity in real-world patients","volume":"25","author":"Lau","year":"2018","journal-title":"Acta Cardiol"},{"key":"2026012115053877200_ehf212547-bib-0013","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.ijcard.2017.10.074","article-title":"Sacubitril\/valsartan and short-term changes in the 6-minute walk test: a pilot study","volume":"252","author":"Beltran","year":"2018","journal-title":"Int J Cardiol"},{"key":"2026012115053877200_ehf212547-bib-0014","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1007\/s12325-018-0710-4","article-title":"An Early View of real-world patient response to sacubitril\/valsartan: a retrospective study of patients with heart failure with reduced ejection fraction","volume":"35","author":"Antol","year":"2018","journal-title":"Adv Ther"},{"key":"2026012115053877200_ehf212547-bib-0015","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5830\/CVJA-2018-039","article-title":"Usefulness of a titration algorithm for de novo users of sacubitril\/valsartan in a tertiary centre heart failure clinic","volume":"29","author":"Laflamme","year":"2018","journal-title":"Cardiovasc J Afr"},{"key":"2026012115053877200_ehf212547-bib-0016","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1002\/ejhf.1465","article-title":"Real-world treatment patterns of sacubitril\/valsartan: a longitudinal cohort study in Germany","volume":"21","author":"Wachter","year":"2019","journal-title":"Eur J Heart Fail"},{"key":"2026012115053877200_ehf212547-bib-0017","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1002\/ejhf.1342","article-title":"Effects of sacubitril\/valsartan on neprilysin targets and the metabolism of natriuretic peptides in chronic heart failure: a mechanistic clinical study","volume":"21","author":"Nougue","year":"2018","journal-title":"Eur J Heart Fail"},{"key":"2026012115053877200_ehf212547-bib-0018","doi-asserted-by":"crossref","DOI":"10.1111\/1755-5922.12435","article-title":"The reverse remodeling response to sacubitril\/valsartan therapy in heart failure with reduced ejection fraction","volume":"36","author":"Martens","year":"2018","journal-title":"Cardiovasc Ther"},{"key":"2026012115053877200_ehf212547-bib-0019","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.ahj.2018.01.004","article-title":"Rationale and design of the comParIson Of sacubitril\/valsartaN versus Enalapril on Effect on nt-pRo-bnp in patients stabilized from an acute Heart Failure episode (PIONEER-HF) trial","volume":"198","author":"Velazquez","year":"2018","journal-title":"Am Heart J"},{"key":"2026012115053877200_ehf212547-bib-0020"},{"key":"2026012115053877200_ehf212547-bib-0021"},{"key":"2026012115053877200_ehf212547-bib-0022","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1002\/ejhf.1402","article-title":"Reduced loop diuretic use in patients taking sacubitril\/valsartan compared with enalapril: the PARADIGM-HF trial","volume":"21","author":"Vardeny","year":"2019","journal-title":"Eur J Heart Fail"},{"key":"2026012115053877200_ehf212547-bib-0023","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.cardfail.2006.09.003","article-title":"The biologic variability of B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide in stable heart failure patients","volume":"13","author":"O'Hanlon","year":"2007","journal-title":"J Card Fail"},{"key":"2026012115053877200_ehf212547-bib-0024","doi-asserted-by":"crossref","first-page":"2425","DOI":"10.1016\/j.jacc.2016.09.931","article-title":"Prognostic implications of changes in N-terminal pro-B-type natriuretic peptide in patients with heart failure","volume":"68","author":"Zile","year":"2016","journal-title":"J Am Coll Cardiol"},{"key":"2026012115053877200_ehf212547-bib-0025","doi-asserted-by":"crossref","DOI":"10.1161\/CIRCHEARTFAILURE.115.002744","article-title":"Influence of ejection fraction on outcomes and efficacy of sacubitril\/valsartan (LCZ696) in heart failure with reduced ejection fraction: the prospective comparison of ARNI with ACEI to determine impact on global mortality and morbidity in heart failure (PARADIGM-HF) Trial","volume":"9","author":"Solomon","year":"2016","journal-title":"Circ Heart Fail"},{"key":"2026012115053877200_ehf212547-bib-0026","doi-asserted-by":"crossref","DOI":"10.1093\/med\/9780198726012.001.0001","volume-title":"The EACVI textbook of echocardiography","author":"Lancellotti","year":"2016"},{"key":"2026012115053877200_ehf212547-bib-0027","doi-asserted-by":"crossref","volume-title":"A language and environment for statistical computing","author":"R Core Team (2018)","DOI":"10.32614\/R.manuals"},{"key":"2026012115053877200_ehf212547-bib-0028","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1097\/FJC.0000000000000603","article-title":"Clinical profile of a nonselected population treated with sacubitril\/valsartan is different from PARADIGM-HF Trial","volume":"72","author":"Vicent","year":"2018","journal-title":"J Cardiovasc Pharmacol"},{"key":"2026012115053877200_ehf212547-bib-0029","first-page":"A17948","article-title":"Reduced loop diuretic use in patients taking sacubitril\/valsartan compared with enalapril: the PARADIGM-HF study","volume":"134","author":"Vardeny","year":"2016","journal-title":"Circulation"},{"key":"2026012115053877200_ehf212547-bib-0030","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1161\/HYPERTENSIONAHA.116.08484","article-title":"Effects of sacubitril\/valsartan (LCZ696) on natriuresis, diuresis, blood pressures, and NT-proBNP in salt-sensitive hypertension","volume":"69","author":"Wang","year":"2017","journal-title":"Hypertension"},{"key":"2026012115053877200_ehf212547-bib-0031","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.amjcard.2017.04.021","article-title":"Changes in loop diuretic dose and outcome after cardiac resynchronization therapy in patients with heart failure and reduced left ventricular ejection fractions","volume":"120","author":"Martens","year":"2017","journal-title":"Am J Cardiol"},{"key":"2026012115053877200_ehf212547-bib-0032","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1111\/bcp.13505","article-title":"Effect of the angiotensin receptor-neprilysin inhibitor sacubitril\/valsartan on the pharmacokinetics and pharmacodynamics of a single dose of furosemide","volume":"84","author":"Ayalasomayajula","year":"2018","journal-title":"Br J Clin Pharmacol"},{"key":"2026012115053877200_ehf212547-bib-0033","article-title":"Independent prognostic value of serum soluble ST2 measurements in patients with heart failure and a reduced ejection fraction in the PARADIGM-HF trial (Prospective comparison of ARNI with ACEI to determine impact on global mortality and morbidity in heart failure)","volume":"11","author":"O'Meara","year":"2018","journal-title":"Circ Heart Fail"},{"key":"2026012115053877200_ehf212547-bib-0034","doi-asserted-by":"crossref","first-page":"2576","DOI":"10.1093\/eurheartj\/ehv330","article-title":"Efficacy and safety of LCZ696 (sacubitril-valsartan) according to age: insights from PARADIGM-HF","volume":"36","author":"Jhund","year":"2015","journal-title":"Eur Heart J"},{"key":"2026012115053877200_ehf212547-bib-0035","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1002\/ejhf.1054","article-title":"Impact of systolic blood pressure on the safety and tolerability of initiating and up-titrating sacubitril\/valsartan in patients with heart failure and reduced ejection fraction: insights from the TITRATION study","volume":"20","author":"Senni","year":"2018","journal-title":"Eur J Heart Fail"}],"container-title":["ESC Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fehf2.12547","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ehf2.12547","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ehf2.12547","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/eschf\/article-pdf\/7\/1\/159\/65804290\/eschf_7_1_159.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eschf\/article-pdf\/7\/1\/159\/65804290\/eschf_7_1_159.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T20:06:50Z","timestamp":1769026010000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eschf\/article\/7\/1\/159\/8373153"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,5]]},"references-count":35,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,1,5]]},"published-print":{"date-parts":[[2020,2,1]]}},"URL":"https:\/\/doi.org\/10.1002\/ehf2.12547","relation":{},"ISSN":["2055-5822"],"issn-type":[{"value":"2055-5822","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,2]]},"published":{"date-parts":[[2020,1,5]]},"assertion":[{"value":"2019-04-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-09-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-01-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}