Is target dose the treatment target? Uptitrating beta-blockers for heart failure in the elderly.
Int J Cardiol. 2011 Nov 29;
Authors: Gelbrich G, Edelmann F, Inkrot S, Lainscak M, Apostolovic S, Neskovic AN, Waagstein F, Loeffler M, Anker SD, Dietz R, Düngen HD,
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 84bpm in groups 1-4, respectively, P<0.001). HR was consistently reduced with each dose level to 65, 63, and 62bpm in groups 1-3 and to 71bpm in group 4 (P<0.001). When adjusted for baseline, HR reduction achieved in group 3 was better than in group 4 (difference -5.4bpm, 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.
PMID: 22133470 [PubMed - as supplied by publisher]