Author + information
- Received July 6, 2015
- Revision received October 9, 2015
- Accepted October 15, 2015
- Published online February 1, 2016.
- Frank Edelmann, MDa,b,c,d,
- Lindy Musial-Bright, MDa,
- Goetz Gelbrich, PhDe,f,
- Tobias Trippel, MDa,c,
- Sara Radenovic, MSca,c,
- Rolf Wachter, MDb,d,
- Simone Inkrot, MScNa,
- Goran Loncar, MDg,
- Elvis Tahirovic, MBAa,c,
- Vera Celic, MDh,
- Jovan Veskovic, Dipl Ecca,
- Marija Zdravkovic, MDi,
- Mitja Lainscak, MDj,k,
- Svetlana Apostolović, MDl,
- Aleksandar N. Neskovic, MDm,
- Burkert Pieske, MDa,c,
- Hans-Dirk Düngen, MDa,c,∗ (, )
- on behalf of the CIBIS-ELD Investigators and Project Multicenter Trials in the Competence Network Heart Failure
- aDepartment of Cardiology, Charité Universitätsmedizin, Campus Virchow-Klinkum, Berlin, Germany
- bDepartment of Cardiology and Pneumology, Göttingen University Medical Center, Göttingen, Germany
- cDZHK Partner Site Berlin, Berlin, Germany
- dDZHK Partner Site Göttingen, Göttingen, Germany
- eInstitute of Clinical Epidemiology and Biometry, University of Würzburg, Würzburg, Germany
- fClinical Trial Center, University Hospital Würzburg, Würzburg, Germany
- gDepartment of Cardiology, Clinical Hospital Zvezdara, Belgrade, Serbia
- hCardiology Department, University Clinical Hospital Center Dr. Dragisa Misovic, Belgrade, Serbia and Faculty of Medicine, University of Belgrade, Belgrade, Serbia
- iDepartment of Cardiology, Faculty of Medicine, University Hospital Medical Center Bezanijska kosa, University of Belgrade, Belgrade, Serbia
- jDepartment of Cardiology and Department of Research and Education, General Hospital Celje, Celje, Slovenia
- kFaculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
- lClinic for Cardiovascular Diseases, Clinical Center Nis, Serbia
- mClinical Hospital Center Zemun, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
- ↵∗Reprint requests and correspondence:
Dr. Hans-Dirk Düngen, Charité Universitätsmedizin, Academic Research Organization, Department of Cardiology, Augustenburger Platz 1, 13353 Berlin, Germany.
Objectives 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] Patients: A Randomised, Double-Blind Multicentre Study [CIBIS-ELD]; ISRCTN34827306)
This study was funded by German Ministry of Education and Research project number 01GI0205. The authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Edemann and Musial-Bright contributed equally to this work.
- Received July 6, 2015.
- Revision received October 9, 2015.
- Accepted October 15, 2015.
- 2016 American College of Cardiology Foundation