title: Titration to target dose of bisoprolol vs. carvedilol in elderly patients with heart failure: the CIBIS-ELD trial.
abstract: OBJECTIVE
  Various beta-blockers with distinct pharmacological profiles are approved in heart failure, yet they remain underused and underdosed. Although potentially of major public health importance, whether one agent is superior in terms of tolerability and optimal dosing has not been investigated. The aim of this study was therefore to compare the tolerability and clinical effects of two proven beta-blockers in elderly patients with heart failure.
  
  
  RESULTS
  We performed a double-blind superiority trial of bisoprolol vs. carvedilol in 883 elderly heart failure patients with reduced or preserved left ventricular ejection fraction in 41 European centres. The primary endpoint was tolerability, defined as reaching and maintaining guideline-recommended target doses after 12 weeks treatment. Adverse events and clinical parameters of patient status were secondary endpoints. None of the beta-blockers was superior with regards to tolerability: 24% [95% confidence interval (CI) 20-28] of patients in the bisoprolol arm and 25% (95% CI 21-29) of patients in the carvedilol arm achieved the primary endpoint (P= 0.64). The use of bisoprolol resulted in greater reduction of heart rate (adjusted mean difference 2.1 b.p.m., 95% CI 0.5-3.6, P= 0.008) and more, dose-limiting, bradycardic adverse events (16 vs. 11%; P= 0.02). The use of carvedilol led to a reduction of forced expiratory volume (adjusted mean difference 50 mL, 95% CI 4-95, P= 0.03) and more, non-dose-limiting, pulmonary adverse events (10 vs. 4%; P < 0.001).
  
  
  CONCLUSIONS
  Overall tolerability to target doses was comparable. The pattern of intolerance, however, was different: bradycardia occurred more often in the bisoprolol group, whereas pulmonary adverse events occurred more often in the carvedilol group. This study is registered with controlled-trials.com, number ISRCTN34827306.
authors.affiliation: Department of Internal Medicine-Cardiology, Charité-Universitätsmedizin, Competence Network Heart Failure, Campus Virchow-Klinkum, Berlin, Germany. hans-dirk.duengen@charite.de
authors.forename: Hans-Dirk
authors.initials: HD
authors.lastname: Düngen
authors.forename: Svetlana
authors.initials: S
authors.lastname: Apostolovic
authors.forename: Simone
authors.initials: S
authors.lastname: Inkrot
authors.forename: Elvis
authors.initials: E
authors.lastname: Tahirovic
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Töpper
authors.forename: Felix
authors.initials: F
authors.lastname: Mehrhof
authors.forename: Christiane
authors.initials: C
authors.lastname: Prettin
authors.forename: Biljana
authors.initials: B
authors.lastname: Putnikovic
authors.forename: Aleksandar N
authors.initials: AN
authors.lastname: Neskovic
authors.forename: Mirjana
authors.initials: M
authors.lastname: Krotin
authors.forename: Dejan
authors.initials: D
authors.lastname: Sakac
authors.forename: Mitja
authors.initials: M
authors.lastname: Lainscak
authors.forename: Frank
authors.initials: F
authors.lastname: Edelmann
authors.forename: Rolf
authors.initials: R
authors.lastname: Wachter
authors.forename: Thomas
authors.initials: T
authors.lastname: Rau
authors.forename: Thomas
authors.initials: T
authors.lastname: Eschenhagen
authors.forename: Wolfram
authors.initials: W
authors.lastname: Doehner
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Anker
authors.forename: Finn
authors.initials: F
authors.lastname: Waagstein
authors.forename: Christoph
authors.initials: C
authors.lastname: Herrmann-Lingen
authors.forename: Goetz
authors.initials: G
authors.lastname: Gelbrich
authors.forename: Rainer
authors.initials: R
authors.lastname: Dietz
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000368:Aged; D017298:Bisoprolol / Q000009:adverse effects / Q000627:therapeutic use*; D002227:Carbazoles / Q000009:adverse effects / Q000627:therapeutic use*; D000077261:Carvedilol; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005060:Europe; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D011412:Propanolamines / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D017298:Bisoprolol