title: Tolerability and Feasibility of Beta-Blocker Titration in HFpEF Versus HFrEF: Insights From the CIBIS-ELD Trial.
abstract: OBJECTIVE
  This study evaluated the tolerability and feasibility of titration of 2 distinctly acting beta-blockers (BB) in elderly heart failure patients with preserved (HFpEF) and reduced (HFrEF) left ventricular ejection fraction.
  
  
  BACKGROUND
  Broad evidence supports the use of BB in HFrEF, whereas the evidence for beta blockade in HFpEF is uncertain.
  
  
  METHODS
  In the CIBIS-ELD (Cardiac Insufficiency Bisoprolol Study in Elderly) trial, patients >65 years of age with HFrEF (n = 626) or HFpEF (n = 250) were randomized to bisoprolol or carvedilol. Both BB were up-titrated to the target or maximum tolerated dose. Follow-up was performed after 12 weeks. HFrEF and HFpEF patients were compared regarding tolerability and clinical effects (heart rate, blood pressure, systolic and diastolic functions, New York Heart Association functional class, 6-minute-walk distance, quality of life, and N-terminal pro-B-type natriuretic peptide).
  
  
  RESULTS
  For both of the BBs, tolerability and daily dose at 12 weeks were similar. HFpEF patients demonstrated higher rates of dose escalation delays and treatment-related side effects. Similar HR reductions were observed in both groups (HFpEF: 6.6 beats/min; HFrEF: 6.9 beats/min, p = NS), whereas greater improvement in NYHA functional class was observed in HFrEF (HFpEF: 23% vs. HFrEF: 34%, p < 0.001). Mean E/e' and left atrial volume index did not change in either group, although E/A increased in HFpEF.
  
  
  CONCLUSIONS
  BB tolerability was comparable between HFrEF and HFpEF. Relevant reductions of HR and blood pressure occurred in both groups. However, only HFrEF patients experienced considerable improvements in clinical parameters and left ventricular function. Interestingly, beta-blockade had no effect on established and prognostic markers of diastolic function in either group. Long-term studies using modern diagnostic criteria for HFpEF are urgently needed to establish whether BB therapy exerts significant clinical benefit in HFpEF. (Comparison of Bisoprolol and Carvedilol in Elderly Heart Failure [HF]
  
  
  METHODS
  A Randomised, Double-Blind Multicentre Study [CIBIS-ELD]; ISRCTN34827306).
authors.affiliation: Department of Cardiology, Charité Universitätsmedizin, Campus Virchow-Klinkum, Berlin, Germany; Department of Cardiology and Pneumology, Göttingen University Medical Center, Göttingen, Germany; DZHK Partner Site Berlin, Berlin, Germany; DZHK Partner Site Göttingen, Göttingen, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Edelmann
authors.affiliation: Department of Cardiology, Charité Universitätsmedizin, Campus Virchow-Klinkum, Berlin, Germany.
authors.forename: Lindy
authors.initials: L
authors.lastname: Musial-Bright
authors.affiliation: Institute of Clinical Epidemiology and Biometry, University of Würzburg, Würzburg, Germany; Clinical Trial Center, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Goetz
authors.initials: G
authors.lastname: Gelbrich
authors.affiliation: Department of Cardiology, Charité Universitätsmedizin, Campus Virchow-Klinkum, Berlin, Germany; DZHK Partner Site Berlin, Berlin, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Trippel
authors.affiliation: Department of Cardiology, Charité Universitätsmedizin, Campus Virchow-Klinkum, Berlin, Germany; DZHK Partner Site Berlin, Berlin, Germany.
authors.forename: Sara
authors.initials: S
authors.lastname: Radenovic
authors.affiliation: Department of Cardiology and Pneumology, Göttingen University Medical Center, Göttingen, Germany; DZHK Partner Site Göttingen, Göttingen, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Wachter
authors.affiliation: Department of Cardiology, Charité Universitätsmedizin, Campus Virchow-Klinkum, Berlin, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Inkrot
authors.affiliation: Department of Cardiology, Clinical Hospital Zvezdara, Belgrade, Serbia.
authors.forename: Goran
authors.initials: G
authors.lastname: Loncar
authors.affiliation: Department of Cardiology, Charité Universitätsmedizin, Campus Virchow-Klinkum, Berlin, Germany; DZHK Partner Site Berlin, Berlin, Germany.
authors.forename: Elvis
authors.initials: E
authors.lastname: Tahirovic
authors.affiliation: Cardiology Department, University Clinical Hospital Center Dr. Dragisa Misovic, Belgrade, Serbia and Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Vera
authors.initials: V
authors.lastname: Celic
authors.affiliation: Department of Cardiology, Charité Universitätsmedizin, Campus Virchow-Klinkum, Berlin, Germany.
authors.forename: Jovan
authors.initials: J
authors.lastname: Veskovic
authors.affiliation: Department of Cardiology, Faculty of Medicine, University Hospital Medical Center Bezanijska kosa, University of Belgrade, Belgrade, Serbia.
authors.forename: Marija
authors.initials: M
authors.lastname: Zdravkovic
authors.affiliation: Department of Cardiology and Department of Research and Education, General Hospital Celje, Celje, Slovenia; Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Mitja
authors.initials: M
authors.lastname: Lainscak
authors.affiliation: Clinic for Cardiovascular Diseases, Clinical Center Nis, Serbia.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Apostolović
authors.affiliation: Clinical Hospital Center Zemun, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Aleksandar N
authors.initials: AN
authors.lastname: Neskovic
authors.affiliation: Department of Cardiology, Charité Universitätsmedizin, Campus Virchow-Klinkum, Berlin, Germany; DZHK Partner Site Berlin, Berlin, Germany.
authors.forename: Burkert
authors.initials: B
authors.lastname: Pieske
authors.affiliation: Department of Cardiology, Charité Universitätsmedizin, Campus Virchow-Klinkum, Berlin, Germany; DZHK Partner Site Berlin, Berlin, Germany. Electronic address: hans-dirk.duengen@charite.de.
authors.forename: Hans-Dirk
authors.initials: HD
authors.lastname: Düngen
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004361:Drug Tolerance; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000502:physiology*; D006801:Humans; D008297:Male; D013318:Stroke Volume / Q000502:physiology*; D013997:Time Factors; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000502:physiology*
chemical_list: D000319:Adrenergic beta-Antagonists
keywords: HFpEF; HFrEF; beta-blockers; heart failure; tolerability