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

• Published in: International journal of cardiology 2012-02, Vol.155 (1), p.160-166
• Main Authors: Gelbrich, Götz, Edelmann, Frank, Inkrot, Simone, Lainscak, Mitja, Apostolovic, Svetlana, Neskovic, Aleksandar N, Waagstein, Finn, Loeffler, Markus, Anker, Stefan D, Dietz, Rainer, Düngen, Hans-Dirk
• Format: Article
• Language: English
• Subjects: Adrenergic beta-Antagonists - administration & dosage; Adrenergic beta-Antagonists - blood; Aged; Aged, 80 and over; Beta-blocker; Biological and medical sciences; Bisoprolol - administration & dosage; Blood Pressure - drug effects; Blood Pressure - physiology; Carbazoles - administration & dosage; Cardiology. Vascular system; Cardiovascular; Dose-Response Relationship, Drug; Double-Blind Method; Drug Delivery Systems - methods; Elderly patients; Female; Guidelines; Heart; Heart failure; Heart Failure - blood; Heart Failure - drug therapy; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Heart rate; Heart Rate - drug effects; Heart Rate - physiology; Humans; Male; Medical sciences; Propanolamines - administration & dosage; Target dose; Treatment Outcome
• ISSN: 0167-5273; 1874-1754
• DOI: 10.1016/j.ijcard.2011.11.018

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.