title: Long-term results of intensified, N-terminal-pro-B-type natriuretic peptide-guided versus symptom-guided treatment in elderly patients with heart failure: five-year follow-up from TIME-CHF.
abstract: BACKGROUND
  Therapy guided by N-terminal-pro-B-type natriuretic peptide (NT-proBNP) levels may improve outcomes in patients with chronic heart failure (HF), especially in younger patients with reduced left ventricular ejection fraction. It remains unclear whether treatment effects persist after discontinuation of the NT-proBNP-guided treatment strategy.
  
  
  RESULTS
  Trial of Intensified versus standard Medical therapy in Elderly patients with Congestive Heart Failure randomized 499 patients with HF aged≥60 years with left ventricular ejection fraction≤45% to intensified, NT-proBNP-guided versus standard, symptom-guided therapy into prespecified age groups (60-74 and ≥75 years) during 18 months. A total of 329 patients (92%) alive at 18 months agreed to long-term follow-up. HF medication was intensified to a larger extent in the NT-proBNP-guided group. During long-term, NT-proBNP-guided therapy did not improve hospital-free (primary end point: hazard ratio, 0.87; 95% confidence interval, 0.71-1.06; P=0.16) or overall survival (hazard ratio, 0.85; 95% confidence interval, 0.64-1.13; P=0.25) but did improve HF hospitalization-free survival (hazard ratio, 0.70; 95% confidence interval, 0.55-0.90; P=0.005). Patients aged 60 to 74 years had benefit from NT-proBNP-guided therapy on the primary end point and HF hospitalization-free survival, whereas patients aged≥75 years did not (P<0.10 for interaction). In landmark analysis, there was no regression to the mean after cessation of the NT-proBNP-guided strategy. More intensified HF medication at month 12 was associated with better long-term HF hospitalization-free and overall survival.
  
  
  CONCLUSIONS
  Intensified, NT-proBNP-guided therapy did not improve the primary end point compared with symptom-guided therapy but did improve HF hospitalization-free survival. Within the subgroup of patients aged 60 to 74 years, it improved clinical outcome including the primary end point. These effects did not disappear after cessation of the NT-proBNP-guided strategy on the long-term. This is possibly attributable to a more intensified HF medical therapy in the NT-proBNP-guided group.
  
  
  BACKGROUND
  URL: http://www.isrctn.org. Unique identifier: ISRCTN43596477.
authors.affiliation: Department of Cardiology, Maastricht University Medical Center, CARIM, Maastricht, The Netherlands.
authors.forename: Sandra
authors.initials: S
authors.lastname: Sanders-van Wijk
authors.forename: Micha T
authors.initials: MT
authors.lastname: Maeder
authors.forename: Fabian
authors.initials: F
authors.lastname: Nietlispach
authors.forename: Hans
authors.initials: H
authors.lastname: Rickli
authors.forename: Werner
authors.initials: W
authors.lastname: Estlinbaum
authors.forename: Paul
authors.initials: P
authors.lastname: Erne
authors.forename: Peter
authors.initials: P
authors.lastname: Rickenbacher
authors.forename: Martin
authors.initials: M
authors.lastname: Peter
authors.forename: Matthias P
authors.initials: MP
authors.lastname: Pfisterer
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Brunner-La Rocca
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000368:Aged; D000369:Aged, 80 and over; D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D019468:Disease Management; D023381:Endpoint Determination; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D012084:Renin-Angiotensin System / Q000187:drug effects; D013318:Stroke Volume / Q000502:physiology*; D015996:Survival Rate; D063189:Symptom Assessment / Q000379:methods*
chemical_list: D000319:Adrenergic beta-Antagonists; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D000451:Mineralocorticoid Receptor Antagonists; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain
keywords: aging; heart failure; pro-brain natriuretic peptide (1–76); prognosis; type-B natriuretic peptide