title: Is target dose the treatment target? Uptitrating beta-blockers for heart failure in the elderly.
abstract: BACKGROUND
  Guideline-recommended beta-blocker (BB) target doses for patients with chronic heart failure can often not be reached. This secondary analysis of the CIBIS-ELD trial was carried out to better understand reasons for not achieving target doses.
  
  
  METHODS
  Changes in heart rate (HR) and other parameters during a 12-week up-titration period in 302 BB naïve patients were evaluated in the subgroups achieving 12.5, 25, 50, and 100% of the target dose (groups 1, 2, 3, and 4, respectively).
  
  
  RESULTS
  Achieved doses predominantly depended on baseline HR (means 68, 74, 76, and 84 bpm in groups 1-4, respectively, P<0.001). HR was consistently reduced with each dose level to 65, 63, and 62 bpm in groups 1-3 and to 71 bpm in group 4 (P<0.001). When adjusted for baseline, HR reduction achieved in group 3 was better than in group 4 (difference -5.4 bpm, P<0.05). More patients in groups 3/4 than in groups 1/2 improved in NYHA class (P = 0.01). NTproBNP increased by 38% in group 4 (P<0.01) but not in the others (P<0.05 between groups). Changes in blood pressure, six-minute walk distance and self-rated health were comparable in all groups.
  
  
  CONCLUSIONS
  The desired effect of HR reduction appears to be a predominant limitation for BB up-titration. Vice versa, achieving the target dose may be a sign of insufficient response rather than successful treatment. In view of these results and the well-known importance of HR for survival, not target doses, but HR control should be given priority in BB treatment for heart failure.
authors: Clinical Trial Centre Leipzig, University of Leipzig, Germany. goetz.gelbrich@zks.uni-leipzig.de
authors: Götz
authors: G
authors: Gelbrich
authors: Frank
authors: F
authors: Edelmann
authors: Simone
authors: S
authors: Inkrot
authors: Mitja
authors: M
authors: Lainscak
authors: Svetlana
authors: S
authors: Apostolovic
authors: Aleksandar N
authors: AN
authors: Neskovic
authors: Finn
authors: F
authors: Waagstein
authors: Markus
authors: M
authors: Loeffler
authors: Stefan D
authors: SD
authors: Anker
authors: Rainer
authors: R
authors: Dietz
authors: Hans-Dirk
authors: HD
authors: Düngen
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage* / Q000097:blood*; D000368:Aged; D000369:Aged, 80 and over; D017298:Bisoprolol / Q000008:administration & dosage; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002227:Carbazoles / Q000008:administration & dosage; D000077261:Carvedilol; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000188:drug therapy*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D011412:Propanolamines / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D017298:Bisoprolol