title: Safety and tolerability of intensified, N-terminal pro brain natriuretic peptide-guided compared with standard medical therapy in elderly patients with congestive heart failure: results from TIME-CHF.
abstract: OBJECTIVE
  NT-proBNP-guided therapy results in intensification of medical heart failure (HF) therapy and is suggested to improve outcome. However, it is feared that an intensified, NT-proBNP-guided therapy carries a risk of adverse effects. Therefore, the safety and tolerability of NT-proBNP-guided therapy in the Trial of Intensified vs standard Medical therapy in Elderly patients with Congestive Heart Failure (TIME-CHF) was assessed.
  
  
  RESULTS
  A total of 495 chronic HF patients, aged ≥60, with an LVEF ≤45%, NYHA class ≥II, randomized to NT-proBNP-guided or symptom-guided therapy and ≥1 month follow-up were included in the present safety analysis. All adverse events (AEs) were recorded during the 18-month trial period. A total of 5212 AEs were noted, 433 of them serious. NT-proBNP-guided therapy led to a higher up-titration of HF medication and was well tolerated, with a dropout rate (12% vs. 11%, P = 1.0) and AE profile [number of AEs/patient-year 4.7 (2.8-9.4) vs. 5.4 (2.7-11.4), P = 0.69; number of severe AEs/patient-year 0.7 (0-2.7) vs. 1.3 (0-3.9), P = 0.21] similar to that of symptom-guided therapy, although most subjects in both treatment groups (96% vs. 95%, P = 0.55) experienced at least one AE. Age and number of co-morbidities were associated with AEs and interacted with the safety profile of NT-proBNP-guided therapy: positive effects were more frequent in younger and less co-morbid patients whereas potential negative effects-although small and related to non-severe AEs only-were only seen in the older and more co-morbid patients.
  
  
  CONCLUSIONS
  NT-proBNP-guided therapy is safe in elderly and highly co-morbid HF patients. Trial registration ISRCTN43596477.
authors.affiliation: Maastricht University Medical Center, CARIM, Maastricht, The Netherlands. sandra.van.wijk@mumc.nl
authors.forename: Sandra
authors.initials: S
authors.lastname: Sanders-van Wijk
authors.forename: Stefano
authors.initials: S
authors.lastname: Muzzarelli
authors.forename: Michael
authors.initials: M
authors.lastname: Neuhaus
authors.forename: Stephanie
authors.initials: S
authors.lastname: Kiencke
authors.forename: Micha
authors.initials: M
authors.lastname: Maeder
authors.forename: Werner
authors.initials: W
authors.lastname: Estlinbaum
authors.forename: Daniel
authors.initials: D
authors.lastname: Tobler
authors.forename: Kurt
authors.initials: K
authors.lastname: Mayer
authors.forename: Paul
authors.initials: P
authors.lastname: Erne
authors.forename: Matthias E
authors.initials: ME
authors.lastname: Pfisterer
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Brunner-La Rocca
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000368:Aged; D000369:Aged, 80 and over; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D004232:Diuretics / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004358:Drug Therapy / Q000379:methods; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000627:therapeutic use*; D013148:Spironolactone / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D004232:Diuretics; D010446:Peptide Fragments; D049994:Sodium Potassium Chloride Symporter Inhibitors; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D013148:Spironolactone
keywords: Ageing; Co-morbidities; Drug therapy; Heart failure; Natriuretic peptide; Safety