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

Eur J Heart Fail. 2011 Oct;13(10):1096-103. doi: 10.1093/eurjhf/hfr078. Epub 2011 Jun 29.


Aim: To determine whether brain natriuretic peptide (BNP)-guided heart failure (HF) treatment improves morbidity and/or mortality when compared with conventional treatment.

Methods 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 <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 <150 ng/L in younger patients and <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 (>30% decrease in baseline BNP value) vs. non-responders found improved survival among responders (P< 0.0001 for the primary outcome), and all of the secondary endpoints were also improved.

Conclusions: 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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / administration & dosage
  • Aged
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage
  • Cardiovascular Agents / administration & dosage*
  • Chronic Disease
  • Disease-Free Survival
  • Female
  • Heart Failure / blood
  • Heart Failure / drug therapy*
  • Heart Failure / mortality
  • Hospitals
  • Humans
  • Male
  • Natriuretic Peptide, Brain / blood*
  • Natriuretic Peptide, Brain / drug effects
  • Norway
  • Severity of Illness Index
  • Sweden
  • Treatment Outcome


  • Adrenergic beta-Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Cardiovascular Agents
  • Natriuretic Peptide, Brain