title: Heart rate following short-term beta-blocker titration predicts all-cause mortality in elderly chronic heart failure patients: insights from the CIBIS-ELD trial.
abstract: OBJECTIVE
  Beta-blockers (BBs) improve outcomes in heart failure. Results from the Cardiac Insufficiency Bisoprolol Study in Elderly (CIBIS-ELD) trial previously demonstrated the feasibility of heart rate, not maximum dose, as a treatment goal. In this pre-specified analysis, we investigated the prognostic value of achieved heart rate after BB optimization on long-term mortality.
  
  
  RESULTS
  Elderly heart failure patients from the CIBIS-ELD trial were invited to participate in a follow-up examination 4 years after the initial 12-week BB up-titration period. The relationship between all-cause mortality, BB dose, and heart rate after titration and potentially confounding clinical variables was analysed by multivariable Cox regression. In total, 728 patients (38% women; mean age 72.9 ± 5.4 years) were included. During a mean follow-up period of 45 ± 9 months, 134 patients (19%) died, thus accumulating 2268 patient-years at risk. There was no significant difference in baseline heart rate for survivors and non-survivors (P = 0.19). In models adjusting for age, sex, BB pre-treatment, ventricular function, heart rate, and NYHA class at baseline, a heart rate increase by 10 b.p.m. following up-titration was associated with a subsequent mortality hazard ratio of 1.19 (95% confidence interval 1.02-1.38, P = 0.023). The heart rate range with the lowest mortality and the fewest treatment-related adverse events was 55-64 b.p.m. The achieved BB dose was not associated with mortality risk.
  
  
  CONCLUSIONS
  The heart rate after up-titration, but not BB dose, predicted all-cause mortality risk in elderly patients with chronic heart failure. These patients should be titrated to resting heart rates between 55 and 64 b.p.m.
authors.affiliation: Charité Universitätsmedizin Berlin, Department of Internal Medicine-Cardiology, Berlin, Germany.
authors.forename: Hans-Dirk
authors.initials: HD
authors.lastname: Düngen
authors.forename: Lindy
authors.initials: L
authors.lastname: Musial-Bright
authors.forename: Simone
authors.initials: S
authors.lastname: Inkrot
authors.forename: Svetlana
authors.initials: S
authors.lastname: Apostolović
authors.forename: Frank
authors.initials: F
authors.lastname: Edelmann
authors.forename: Mitja
authors.initials: M
authors.lastname: Lainščak
authors.forename: Nikola
authors.initials: N
authors.lastname: Sekularac
authors.forename: Stefan
authors.initials: S
authors.lastname: Störk
authors.forename: Elvis
authors.initials: E
authors.lastname: Tahirovic
authors.forename: Verena
authors.initials: V
authors.lastname: Tscholl
authors.forename: Florian
authors.initials: F
authors.lastname: Krackhardt
authors.forename: Goran
authors.initials: G
authors.lastname: Loncar
authors.forename: Tobias D
authors.initials: TD
authors.lastname: Trippel
authors.forename: Götz
authors.initials: G
authors.lastname: Gelbrich
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000368:Aged; D000369:Aged, 80 and over; D017298:Bisoprolol / Q000627:therapeutic use; D002227:Carbazoles / Q000627:therapeutic use; D000077261:Carvedilol; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D006339:Heart Rate; D006801:Humans; D008297:Male; D009026:Mortality; D011379:Prognosis; D011412:Propanolamines / Q000627:therapeutic use; D016016:Proportional Hazards Models; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D017298:Bisoprolol
keywords: Beta-blockers; Elderly; Heart failure; Heart rate