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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
Division of Cardiology, Department of Medicine, County Hospital Ryhov, Jönköping, Sweden.
Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
Institution of Public Health and Clinical Medicine, Umeå University, Sweden.
Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.ORCID iD: 0000-0001-6353-8041
2011 (English)In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 13, no 10, 1096-1103 p.Article in journal (Refereed) Published
Abstract [en]

Aim To determine whether brain natriuretic peptide (BNP)-guided heart failure (HF) treatment improves morbidity and/or mortality when compared with conventional treatment. less thanbrgreater than less thanbrgreater thanMethods and results UPSTEP was an investigator-initiated, randomized, parallel group, multicentre study with a PROBE design. Symptomatic patients with worsening HF, New York Heart Association class II-IV, ejection fraction andlt;40% and elevated BNP levels, were included. All patients (n = 279) were treated according to recommended guidelines and randomized to BNP-guided (BNP) or to conventional (CTR) HF treatment. The goal was to reduce BNP levels to andlt;150 ng/L in younger patients and andlt;300 ng/L in elderly patients, respectively. The primary outcome was a composite of death due to any cause, need for hospitalization and worsening HF. The study groups were well matched, including for BNP concentration at entry (mean: 808 vs. 899 ng/L; P = 0.34). There were no significant differences between the groups regarding either the primary outcome (P = 0.18) or any of the secondary endpoints. There were no differences for the pre-specified analyses; days out of hospital, and younger vs. elderly. A subgroup analysis comparing treatment responders (andgt;30% decrease in baseline BNP value) vs. non-responders found improved survival among responders (P andlt; 0.0001 for the primary outcome), and all of the secondary endpoints were also improved. less thanbrgreater than less thanbrgreater thanConclusions Morbidity and mortality were not improved by HF treatment guided by BNP levels. However, BNP responders had a significantly better clinical outcome than non-responders. Future research is needed to elucidate the responsible pathophysiological mechanisms in this sub-population.

Place, publisher, year, edition, pages
Oxford University Press, 2011. Vol. 13, no 10, 1096-1103 p.
Keyword [en]
PROBE design, Systolic heart failure, Natriuretic peptides, BNP-guided treatment
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-71379DOI: 10.1093/eurjhf/hfr078ISI: 000295169600009OAI: diva2:448065

Funding Agencies|Swedish Heart-Lung Foundation||Regional Research Foundation in South-eastern Sweden||Regional Research Foundation in Northern Sweden||Biosite International||Infiniti Medical AB||

Available from: 2011-10-14 Created: 2011-10-14 Last updated: 2016-02-03
In thesis
1. Heart failure: biomarker effect and influence on quality of life
Open this publication in new window or tab >>Heart failure: biomarker effect and influence on quality of life
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background and aims: Heart failure (HF) is a life threatening condition and optimal handling is necessary to reduce risk of therapy failure. The aims of this thesis were: (Paper I) to examine whether BNP (B-type natriuretic peptide)-guided HF treatment improves morbidity and mortality when compared with HF therapy implemented by a treating physician at sites experienced in managing patients with HF according to guidelines; (Paper II) to investigate how to define a responder regarding optimal cut-off level of BNP to predict death, need for hospitalisation, and worsening HF and to determine the optimal time to apply the chosen cut-off value; (Paper III) to evaluate how Health-Related Quality of Life (HR-QoL) is influenced by natriuretic peptide guiding and to study how HR-QoL is affected in responders compared to non-responders; (Paper IV) to evaluate the impact of patient age on clinical outcomes, and to evaluate the impact of duration of the HF disease on outcomes and the impact of age and HF duration on BNP concentration.

Methods: A randomized, parallel group, multi-centre study was undertaken on 279 patients with HF and who had experienced an episode of worsening HF with increased BNP concentration. The control group (n=132) was treated according to HF guidelines and in the BNP-guided group (n=147) the HF treatment algorithm goal was to reduce BNP concentration to < 150 ng/L in patients < 75 years and <300 ng/L in patients > 75 years (Paper I), and to define the optimal percentage decrease in BNP and at what point during the follow-up to apply the definition (Paper II). To compare the BNP-guided group with the conventional HF treated group (Paper I), and responders and non-responders (Paper II) regarding HR-QoL measured with Short Form 36 (SF-36) at study start and at study end (Paper III) and to evaluate if age or HF duration influenced the HF outcomes and the influence of BNP on age and HF duration (Paper IV).

Results: The primary outcome (mortality, hospitalisation and worsening HF) was not improved by BNP-guided HF treatment compared to conventional HF treatment or in any of the secondary outcome variables (Paper I). Applying a BNP decrease of at least 40 percent in week 16 (compared to study start) and/or a BNP<300 ng/L demonstrated the best risk reduction for cardiovascular mortality, by 78 percent and 89 percent respectively for HF mortality (Paper II). The HR-QoL improved in four domains in the BNP-guided group and in the control group in six of eight domains; however there were no significant differences between the groups (Paper III). For responders the within group analysis showed improvement in four domains compared to the non-responders that improved in one domain; however there were no significant differences between the two groups. There were improvements in HR-QoL in all four groups (Paper III). Age did not influence outcome but HF duration did. HF duration was divided into three groups: HF duration less than 1 year (group 1), 1-5 years (group 2) and >5 years (group 3). A 1.65-fold increased risk could be demonstrated in those with HF duration of more than five years compared to patients with short HF duration. The BNP concentration was increased with increased age, and there was a better response regarding BNP decrease in NP-guiding in patients with short HF duration, independent of age (Paper IV).

Conclusions: There were no significant differences between BNP-guided HF treatment group and the group with conventional HF treatment as regards mortality, hospitalisation or HR-QoL. The responders to HF treatment showed a significantly better outcome in mortality and hospitalisation compared to non-responders but no significant differences in HR-QoL. The duration of HF might be an important factor to consider in HF treatment by BNP-guiding in the future.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2016. 123 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1499
Heart failure, Biomarker, B-type natriuretic peptide, Heart failure treatment, B-type Natriuretic Peptide guided heart failure treatment, Responders, Health-related quality of life, Heart failure duration, Outcomes
National Category
Cardiac and Cardiovascular Systems
urn:nbn:se:liu:diva-124560 (URN)10.3384/diss.diva-124560 (DOI)978-91-7685-869-1 (Print) (ISBN)
Public defence
2016-03-04, Belladonna, Campus US, Linköping, 09:00 (Swedish)
Swedish Heart Lung Foundation
Available from: 2016-02-03 Created: 2016-02-03 Last updated: 2016-02-09Bibliographically approved

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