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.
abstract: BACKGROUND
  It is uncertain whether intensified heart failure therapy guided by N-terminal brain natriuretic peptide (BNP) is superior to symptom-guided therapy.
  
  
  OBJECTIVE
  To compare 18-month outcomes of N-terminal BNP-guided vs symptom-guided heart failure therapy.
  
  
  METHODS
  Randomized controlled multicenter Trial of Intensified vs Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) of 499 patients aged 60 years or older with systolic heart failure (ejection fraction < or = 45%), New York Heart Association (NYHA) class of II or greater, prior hospitalization for heart failure within 1 year, and N-terminal BNP level of 2 or more times the upper limit of normal. The study had an 18-month follow-up and it was conducted at 15 outpatient centers in Switzerland and Germany between January 2003 and June 2008.
  
  
  METHODS
  Uptitration of guideline-based treatments to reduce symptoms to NYHA class of II or less (symptom-guided therapy) and BNP level of 2 times or less the upper limit of normal and symptoms to NYHA class of II or less (BNP-guided therapy).
  
  
  METHODS
  Primary outcomes were 18-month survival free of all-cause hospitalizations and quality of life as assessed by structured validated questionnaires.
  
  
  RESULTS
  Heart failure therapy guided by N-terminal BNP and symptom-guided therapy resulted in similar rates of survival free of all-cause hospitalizations (41% vs 40%, respectively; hazard ratio [HR], 0.91 [95% CI, 0.72-1.14]; P = .39). Patients' quality-of-life metrics improved over 18 months of follow-up but these improvements were similar in both the N-terminal BNP-guided and symptom-guided strategies. Compared with the symptom-guided group, survival free of hospitalization for heart failure, a secondary end point, was higher among those in the N-terminal BNP-guided group (72% vs 62%, respectively; HR, 0.68 [95% CI, 0.50-0.92]; P = .01). Heart failure therapy guided by N-terminal BNP improved outcomes in patients aged 60 to 75 years but not in those aged 75 years or older (P < .02 for interaction)
  
  
  CONCLUSIONS
  Heart failure therapy guided by N-terminal BNP did not improve overall clinical outcomes or quality of life compared with symptom-guided treatment.
  
  
  BACKGROUND
  isrctn.org Identifier: ISRCTN43596477.
authors.affiliation: Department of Cardiology, University Hospital Basel, CH-4031 Basel, Switzerland. pfisterer@email.ch
authors.forename: Matthias
authors.initials: M
authors.lastname: Pfisterer
authors.forename: Peter
authors.initials: P
authors.lastname: Buser
authors.forename: Hans
authors.initials: H
authors.lastname: Rickli
authors.forename: Marc
authors.initials: M
authors.lastname: Gutmann
authors.forename: Paul
authors.initials: P
authors.lastname: Erne
authors.forename: Peter
authors.initials: P
authors.lastname: Rickenbacher
authors.forename: André
authors.initials: A
authors.lastname: Vuillomenet
authors.forename: Urs
authors.initials: U
authors.lastname: Jeker
authors.forename: Paul
authors.initials: P
authors.lastname: Dubach
authors.forename: Hansjürg
authors.initials: H
authors.lastname: Beer
authors.forename: Se-Il
authors.initials: SI
authors.lastname: Yoon
authors.forename: Thomas
authors.initials: T
authors.lastname: Suter
authors.forename: Hans H
authors.initials: HH
authors.lastname: Osterhues
authors.forename: Michael M
authors.initials: MM
authors.lastname: Schieber
authors.forename: Patrick
authors.initials: P
authors.lastname: Hilti
authors.forename: Ruth
authors.initials: R
authors.lastname: Schindler
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Brunner-La Rocca
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage; D000368:Aged; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D015415:Biomarkers / Q000097:blood; D002317:Cardiovascular Agents / Q000008:administration & dosage*; D004077:Digoxin / Q000008:administration & dosage; D018572:Disease-Free Survival; D004232:Diuretics / Q000008:administration & dosage; D005260:Female; D005858:Germany; D006333:Heart Failure / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020097:Natriuretic Peptide, Brain / Q000097:blood* / Q000187:drug effects; D009566:Nitrates / Q000008:administration & dosage; D016017:Odds Ratio; D010446:Peptide Fragments / Q000097:blood* / Q000187:drug effects; D016016:Proportional Hazards Models; D011788:Quality of Life; D012720:Severity of Illness Index; D013318:Stroke Volume; D011795:Surveys and Questionnaires; D013557:Switzerland; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D002317:Cardiovascular Agents; D004232:Diuretics; D009566:Nitrates; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D004077:Digoxin