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.
abstract: OBJECTIVE
  To determine whether brain natriuretic peptide (BNP)-guided heart failure (HF) treatment improves morbidity and/or mortality when compared with conventional treatment.
  
  
  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.
authors.affiliation: Division of Cardiology, Department of Medicine, County Hospital Ryhov, Jönköping, Sweden. patric.karlstrom@lj.se
authors.forename: Patric
authors.initials: P
authors.lastname: Karlström
authors.forename: Urban
authors.initials: U
authors.lastname: Alehagen
authors.forename: Kurt
authors.initials: K
authors.lastname: Boman
authors.forename: Ulf
authors.initials: U
authors.lastname: Dahlström
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D002317:Cardiovascular Agents / Q000008:administration & dosage*; D002908:Chronic Disease; D018572:Disease-Free Survival; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D006761:Hospitals; D006801:Humans; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood* / Q000187:drug effects; D009664:Norway; D012720:Severity of Illness Index; D013548:Sweden; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D002317:Cardiovascular Agents; D020097:Natriuretic Peptide, Brain