{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:06:55Z","timestamp":1791295615117,"version":"4.1.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2015,9,30]],"date-time":"2015-09-30T00:00:00Z","timestamp":1443571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Previous analyses suggest that heart failure (HF) therapy guided by (N-terminal pro-)brain natriuretic peptide (NT-proBNP) might be dependent on left ventricular ejection fraction, age and co-morbidities, but the reasons remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>To determine interactions between (NT-pro)BNP-guided therapy and HF with reduced [ejection fraction (EF) \u226445%; HF with reduced EF (HFrEF), n = 1731] vs. preserved EF [EF &amp;gt; 45%; HF with preserved EF (HFpEF), n = 301] and co-morbidities (hypertension, renal failure, chronic obstructive pulmonary disease, diabetes, cerebrovascular insult, peripheral vascular disease) on outcome, individual patient data (n = 2137) from eight NT-proBNP guidance trials were analysed using Cox-regression with multiplicative interaction terms. Endpoints were mortality and admission because of HF. Whereas in HFrEF patients (NT-pro)BNP-guided compared with symptom-guided therapy resulted in lower mortality [hazard ratio (HR) = 0.78, 95% confidence interval (CI) 0.62\u20130.97, P = 0.03] and fewer HF admissions (HR = 0.80, 95% CI 0.67\u20130.97, P = 0.02), no such effect was seen in HFpEF (mortality: HR = 1.22, 95% CI 0.76\u20131.96, P = 0.41; HF admissions HR = 1.01, 95% CI 0.67\u20131.53, P = 0.97; interactions P &amp;lt; 0.02). Age (74 \u00b1 11 years) interacted with treatment strategy allocation independently of EF regarding mortality (P = 0.02), but not HF admission (P = 0.54). The interaction of age and mortality was explained by the interaction of treatment strategy allocation with co-morbidities. In HFpEF, renal failure provided strongest interaction (P &amp;lt; 0.01; increased risk of (NT-pro)BNP-guided therapy if renal failure present), whereas in HFrEF patients, the presence of at least two of the following co-morbidities provided strongest interaction (P &amp;lt; 0.01; (NT-pro)BNP-guided therapy beneficial only if none or one of chronic obstructive pulmonary disease, diabetes, cardiovascular insult, or peripheral vascular disease present). (NT-pro)BNP-guided therapy was harmful in HFpEF patients without hypertension (P = 0.02).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The benefits of therapy guided by (NT-pro)BNP were present in HFrEF only. Co-morbidities seem to influence the response to (NT-pro)BNP-guided therapy and may explain the lower efficacy of this approach in elderly patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.401","type":"journal-article","created":{"date-parts":[[2015,9,30]],"date-time":"2015-09-30T04:23:54Z","timestamp":1443587034000},"page":"1252-1261","source":"Crossref","is-referenced-by-count":84,"title":["Which Heart Failure Patients Profit from Natriuretic Peptide Guided Therapy? a Meta-Analysis from Individual Patient Data of Randomized Trials"],"prefix":"10.1093","volume":"17","author":[{"given":"Hans-Peter","family":"Brunner-La Rocca","sequence":"first","affiliation":[{"name":"Department of Cardiology, Maastricht University Medical Centre , PO Box 5800, NL\u20136202AZ, Maastricht ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc","family":"Eurlings","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Maastricht University Medical Centre , PO Box 5800, NL\u20136202AZ, Maastricht ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Mark","family":"Richards","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Otago Christchurch , Christchurch Hospital, Christchurch ,","place":["New Zealand"]},{"name":"National University Heart Centre Singapore \u00a0","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James L.","family":"Januzzi","sequence":"additional","affiliation":[{"name":"Cardiology Division, Massachusetts General Hospital , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias E.","family":"Pfisterer","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Hospital Basel , Basel ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf","family":"Dahlstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Department of Medical and Health Sciences, Linkoping University, Department of Cardiology , Linkoping ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yigal M.","family":"Pinto","sequence":"additional","affiliation":[{"name":"Academic Medical Centre , Amsterdam ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patric","family":"Karlstr\u00f6m","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, County Hospital Ryhov , Jonkoping ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Erntell","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital , Stockholm ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf","family":"Berger","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Medical University of Vienna , Vienna ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Persson","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital , Stockholm ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M.","family":"O\u2019Connor","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Duke University Medical Center , Durham, NC ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deddo","family":"Moertl","sequence":"additional","affiliation":[{"name":"Department of Cardiology, LKH , St Poelten ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna K.","family":"Gaggin","sequence":"additional","affiliation":[{"name":"Cardiology Division, Massachusetts General Hospital , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M.","family":"Frampton","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Otago Christchurch , Christchurch Hospital, Christchurch ,","place":["New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Gary","family":"Nicholls","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Otago Christchurch , Christchurch Hospital, Christchurch ,","place":["New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard W.","family":"Troughton","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Otago Christchurch , Christchurch Hospital, Christchurch ,","place":["New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,9,30]]},"reference":[{"key":"2026011921104202500_ejhf401-bib-0001","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1093\/eurheartj\/ehu090","article-title":"Effect of B-type natriuretic peptide guided treatment of chronic heart failure on total mortality and hospitalisation: an individual patient meta-analysis","volume":"35","author":"Troughton","year":"2014","journal-title":"Eur Heart J"},{"key":"2026011921104202500_ejhf401-bib-0002","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1016\/j.hlc.2013.03.077","article-title":"B-type natriuretic peptide-guided chronic heart failure therapy: a meta-analysis of 11 randomised controlled trials","volume":"22","author":"Li","year":"2013","journal-title":"Heart Lung Circ"},{"key":"2026011921104202500_ejhf401-bib-0003","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0058287","article-title":"Natriuretic peptide-guided therapy in chronic heart failure: a meta-analysis of 2,686 patients in 12 randomized trials","volume":"8","author":"Savarese","year":"2013","journal-title":"PLoSOne"},{"key":"2026011921104202500_ejhf401-bib-0004","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1093\/eurjhf\/hfs105","article-title":"ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC","volume":"14","author":"McMurray","year":"2012","journal-title":"Eur J Heart Fail"},{"key":"2026011921104202500_ejhf401-bib-0005","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1056\/NEJMoa1313731","article-title":"Spironolactone for heart failure with preserved ejection fraction","volume":"370","author":"Pitt","year":"2014","journal-title":"N Engl J Med"},{"key":"2026011921104202500_ejhf401-bib-0006","doi-asserted-by":"crossref","first-page":"2338","DOI":"10.1093\/eurheartj\/ehl250","article-title":"The perindopril in elderly people with chronic heart failure (PEP-CHF) study","volume":"27","author":"Cleland","year":"2006","journal-title":"Eur Heart J"},{"key":"2026011921104202500_ejhf401-bib-0007","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.1016\/j.jacc.2012.04.064","article-title":"What have we learned about patients with heart failure and preserved ejection fraction from DIG-PEF, CHARM-preserved, and I-PRESERVE?","volume":"60","author":"Campbell","year":"2012","journal-title":"J Am Coll Cardiol"},{"key":"2026011921104202500_ejhf401-bib-0008","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.jacc.2009.08.078","article-title":"N-terminal pro-B-type natriuretic peptide-guided, intensive patient management in addition to multidisciplinary care in chronic heart failure a 3-arm, prospective, randomized pilot study","volume":"55","author":"Berger","year":"2010","journal-title":"J Am Coll Cardiol"},{"key":"2026011921104202500_ejhf401-bib-0009","doi-asserted-by":"crossref","first-page":"2090","DOI":"10.1016\/j.jacc.2010.07.030","article-title":"Management of chronic heart failure guided by individual N-terminal pro-B-type natriuretic peptide targets: results of the PRIMA (Can PRo-brain-natriuretic peptide guided therapy of chronic heart failure IMprove heart fAilure morbidity and mortality?) study","volume":"56","author":"Eurlings","year":"2010","journal-title":"J Am Coll Cardiol"},{"key":"2026011921104202500_ejhf401-bib-0010","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1016\/j.jacc.2011.03.072","article-title":"Use of amino-terminal pro-B-type natriuretic peptide to guide outpatient therapy of patients with chronic left ventricular systolic dysfunction","volume":"58","author":"Januzzi","year":"2011","journal-title":"J Am Coll Cardiol"},{"key":"2026011921104202500_ejhf401-bib-0011","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1093\/eurjhf\/hfr078","article-title":"Brain natriuretic peptide-guided treatment does not improve morbidity and mortality in extensively treated patients with chronic heart failure: responders to treatment have a significantly better outcome","volume":"13","author":"Karlstrom","year":"2011","journal-title":"Eur J Heart Fail"},{"key":"2026011921104202500_ejhf401-bib-0012","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.jacc.2009.02.095","article-title":"N-terminal pro-B-type natriuretic peptide-guided treatment for chronic heart failure: results from the BATTLESCARRED (NT-proBNP-Assisted Treatment To Lessen Serial Cardiac Readmissions and Death) trial","volume":"55","author":"Lainchbury","year":"2010","journal-title":"J Am Coll Cardiol"},{"key":"2026011921104202500_ejhf401-bib-0013","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1093\/eurjhf\/hfq169","article-title":"Improved pharmacological therapy of chronic heart failure in primary care: a randomized Study of NT-proBNP Guided Management of Heart Failure\u2014SIGNAL-HF (Swedish Intervention study\u2014Guidelines and NT-proBNP AnaLysis in Heart Failure)","volume":"12","author":"Persson","year":"2010","journal-title":"Eur J Heart Fail"},{"key":"2026011921104202500_ejhf401-bib-0014","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1001\/jama.2009.2","article-title":"BNP-guided vs symptom-guided heart failure therapy: the Trial of Intensified vs Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) randomized trial","volume":"301","author":"Pfisterer","year":"2009","journal-title":"JAMA"},{"key":"2026011921104202500_ejhf401-bib-0015","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1016\/S0140-6736(00)02060-2","article-title":"Treatment of heart failure guided by plasma aminoterminal brain natriuretic peptide (N-BNP) concentrations","volume":"355","author":"Troughton","year":"2000","journal-title":"Lancet"},{"key":"2026011921104202500_ejhf401-bib-0016","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/j.cardfail.2011.04.012","article-title":"The STARBRITE trial: a randomized, pilot study of B-type natriuretic peptide-guided therapy in patients with advanced heart failure","volume":"17","author":"Shah","year":"2011","journal-title":"J Card Fail"},{"key":"2026011921104202500_ejhf401-bib-0017","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1093\/eurjhf\/hft076","article-title":"N-terminal pro brain natriuretic peptide-guided management in patients with heart failure and preserved ejection fraction: findings from the Trial of Intensified vs. standard medical therapy in elderly patients with congestive heart failure (TIME-CHF)","volume":"15","author":"Maeder","year":"2013","journal-title":"Eur J Heart Fail"},{"key":"2026011921104202500_ejhf401-bib-0018","doi-asserted-by":"crossref","first-page":"2473","DOI":"10.1056\/NEJMra054415","article-title":"Assessing kidney function \u2013 measured and estimated glomerular filtration rate","volume":"354","author":"Stevens","year":"2006","journal-title":"N Engl J Med"},{"key":"2026011921104202500_ejhf401-bib-0019","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1007\/s11897-014-0186-8","article-title":"Polypharmacy in heart failure patients","volume":"11","author":"Mastromarino","year":"2014","journal-title":"Curr Heart Fail Rep"},{"key":"2026011921104202500_ejhf401-bib-0020","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1093\/eurheartj\/ehi115","article-title":"Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS)","volume":"26","author":"Flather","year":"2005","journal-title":"Eur Heart J"},{"key":"2026011921104202500_ejhf401-bib-0021","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1056\/NEJMoa1009492","article-title":"Eplerenone in patients with systolic heart failure and mild symptoms","volume":"364","author":"Zannad","year":"2011","journal-title":"N Engl J Med"},{"key":"2026011921104202500_ejhf401-bib-0022","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1001\/archinternmed.2007.80","article-title":"Incidence and prevalence of heart failure in elderly persons, 1994\u20132003","volume":"168","author":"Curtis","year":"2008","journal-title":"Arch Intern Med"},{"key":"2026011921104202500_ejhf401-bib-0023","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1001\/archinte.162.15.1689","article-title":"Prognosis and determinants of survival in patients newly hospitalized for heart failure: a population-based study","volume":"162","author":"Jong","year":"2002","journal-title":"Arch Intern Med"},{"key":"2026011921104202500_ejhf401-bib-0024","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1002\/ejhf.210","article-title":"Impact of worsening renal function related to medication in heart failure","volume":"17","author":"Brunner-La Rocca","year":"2015","journal-title":"Eur J Heart Fail"},{"key":"2026011921104202500_ejhf401-bib-0025","doi-asserted-by":"crossref","first-page":"2706","DOI":"10.1093\/eurheartj\/ehi499","article-title":"Under-utilization of evidence-based drug treatment in patients with heart failure is only partially explained by dissimilarity to patients enrolled in landmark trials: a report from the Euro Heart Survey on Heart Failure","volume":"26","author":"Lenzen","year":"2005","journal-title":"Eur Heart J"},{"key":"2026011921104202500_ejhf401-bib-0026","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1093\/eurheartj\/ehr254","article-title":"The survival of patients with heart failure with preserved or reduced left ventricular ejection fraction: an individual patient data meta-analysis","volume":"33","author":"Meta-analysis Global Group in Chronic Heart Failure (MAGGIC)","year":"2012","journal-title":"Eur Heart J"},{"key":"2026011921104202500_ejhf401-bib-0027","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1056\/NEJMoa051530","article-title":"Outcome of heart failure with preserved ejection fraction in a population-based study","volume":"355","author":"Bhatia","year":"2006","journal-title":"N Engl J Med"},{"key":"2026011921104202500_ejhf401-bib-0028","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1056\/NEJMoa052256","article-title":"Trends in prevalence and outcome of heart failure with preserved ejection fraction","volume":"355","author":"Owan","year":"2006","journal-title":"N Engl J Med"},{"key":"2026011921104202500_ejhf401-bib-0029","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1001\/jama.2012.14785","article-title":"Association between use of renin\u2013angiotensin system antagonists and mortality in patients with heart failure and preserved ejection fraction","volume":"308","author":"Lund","year":"2012","journal-title":"JAMA"},{"key":"2026011921104202500_ejhf401-bib-0030","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1093\/eurjhf\/hfs049","article-title":"Relationship between plasma concentrations of N-terminal pro brain natriuretic peptide and the characteristics and outcome of patients with a clinical diagnosis of diastolic heart failure: a report from the PEP-CHF study","volume":"14","author":"Cleland","year":"2012","journal-title":"Eur J Heart Fail"},{"key":"2026011921104202500_ejhf401-bib-0031","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.ehj.2003.10.030","article-title":"The comparative prognostic value of plasma neurohormones at baseline in patients with heart failure enrolled in Val-HeFT","volume":"25","author":"Latini","year":"2004","journal-title":"Eur Heart J."}],"container-title":["European Journal of Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fejhf.401","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/17\/12\/1252\/66423252\/eurjhf_17_12_1252.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eurjhf\/article-pdf\/17\/12\/1252\/66423252\/eurjhf_17_12_1252.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T02:11:38Z","timestamp":1768875098000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eurjhf\/article\/17\/12\/1252\/8426420"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,9,30]]},"references-count":31,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2015,9,30]]},"published-print":{"date-parts":[[2015,12,1]]}},"URL":"https:\/\/doi.org\/10.1002\/ejhf.401","relation":{},"ISSN":["1388-9842","1879-0844"],"issn-type":[{"value":"1388-9842","type":"print"},{"value":"1879-0844","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2015,12]]},"published":{"date-parts":[[2015,9,30]]}}}