Is target dose the treatment target? Uptitrating beta-blockers for heart failure in the elderly

Int J Cardiol. 2012 Feb 23;155(1):160-6. doi: 10.1016/j.ijcard.2011.11.018. Epub 2011 Nov 30.

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.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / administration & dosage*
  • Adrenergic beta-Antagonists / blood*
  • Aged
  • Aged, 80 and over
  • Bisoprolol / administration & dosage
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Carbazoles / administration & dosage
  • Carvedilol
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Delivery Systems / methods
  • Female
  • Heart Failure / blood*
  • Heart Failure / drug therapy*
  • Heart Rate / drug effects
  • Heart Rate / physiology
  • Humans
  • Male
  • Propanolamines / administration & dosage
  • Treatment Outcome

Substances

  • Adrenergic beta-Antagonists
  • Carbazoles
  • Propanolamines
  • Carvedilol
  • Bisoprolol