title: Does the target dose of neurohormonal blockade matter for outcome in Systolic heart failure in octogenarians?
abstract: BACKGROUND
  In elderly patients with chronic heart failure (CHF), a gap exists between widespread use of lower doses of angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin-receptor blockers (ARBs) and β-blockers (BBs) and guideline recommendations. Therefore, the aim of the present study was to investigate whether patients receiving ≥ 50% target dose outperform those receiving <50% target dose, despite maximum up-titration, and whether the target dose outperforms all other doses.
  
  
  RESULTS
  Patients (n=185) aged ≥ 80 years with CHF and left ventricular ejection fraction ≤ 40% referred (between January 2000 and January 2008) to two CHF outpatient clinics at two university hospitals, were included and retrospectively studied. Of the study population, 53% received the target dose of ACEIs/ARBs, whereas 26% received <50% of the target dose. Half received <50% of the target dose of BBs and 21% received the target dose. After ≥ 5 years of follow-up, all-cause mortality was 76.8%. Patients who received the target dose of ACEIs/ARBs had higher survival rates from all-cause mortality than those receiving <50% of target dose (HR=0.6, 95%CI 0.4-0.9, P=0.033), but those receiving ≥ 50% of target dose did not statistically differ from those who achieved target dose. This dose-survival relationship was not the case for BBs.
  
  
  CONCLUSIONS
  Target dose of ACEIs/ARBs is associated with reduced all-cause five-year mortality in very old patients with systolic heart failure, despite that this was achievable in only about half of the patients. However, the clinical outcome of BB therapy is independent of BB dose when the target heart rate is achieved.
authors.affiliation: Department of Molecular and Clinical Medicine, Sahlgrenska Academy, Sahlgrenska University Hospital (SU)/Östra Hospital, Sweden. Electronic address: salim.barywani@vgregion.se.
authors.forename: Salim Bary
authors.initials: SB
authors.lastname: Barywani
authors.affiliation: Department of Molecular and Clinical Medicine, Sahlgrenska Academy, Sahlgrenska University Hospital (SU)/Östra Hospital, Sweden.
authors.forename: Constantinos
authors.initials: C
authors.lastname: Ergatoudes
authors.affiliation: Department of Molecular and Clinical Medicine, Sahlgrenska Academy, Sahlgrenska University Hospital (SU)/Östra Hospital, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Schaufelberger
authors.affiliation: Centre for Applied Biostatistics, Sahlgrenska Academy, University of Gothenburg, Sweden.
authors.forename: Max
authors.initials: M
authors.lastname: Petzold
authors.affiliation: Department of Molecular and Clinical Medicine, Sahlgrenska Academy, Sahlgrenska University Hospital (SU)/Östra Hospital, Sweden.
authors.forename: Michael L X
authors.initials: ML
authors.lastname: Fu
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D000369:Aged, 80 and over; D057911:Angiotensin Receptor Antagonists / Q000008:administration & dosage*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D005260:Female; D054143:Heart Failure, Systolic / Q000188:drug therapy*; D006801:Humans; D008297:Male; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors
keywords: ACEIs/ARBs; Beta-blockers; Mortality; Octogenarians; Systolic heart failure; Target dose