Frank Edelmann1, Lindy Musial-Bright2, Goetz Gelbrich3, Tobias Trippel4, Sara Radenovic4, Rolf Wachter5, Simone Inkrot2, Goran Loncar6, Elvis Tahirovic4, Vera Celic7, Jovan Veskovic2, Marija Zdravkovic8, Mitja Lainscak9, Svetlana Apostolović10, Aleksandar N Neskovic11, Burkert Pieske4, Hans-Dirk Düngen12. 1. 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. 2. Department of Cardiology, Charité Universitätsmedizin, Campus Virchow-Klinkum, Berlin, Germany. 3. Institute of Clinical Epidemiology and Biometry, University of Würzburg, Würzburg, Germany; Clinical Trial Center, University Hospital Würzburg, Würzburg, Germany. 4. Department of Cardiology, Charité Universitätsmedizin, Campus Virchow-Klinkum, Berlin, Germany; DZHK Partner Site Berlin, Berlin, Germany. 5. Department of Cardiology and Pneumology, Göttingen University Medical Center, Göttingen, Germany; DZHK Partner Site Göttingen, Göttingen, Germany. 6. Department of Cardiology, Clinical Hospital Zvezdara, Belgrade, Serbia. 7. Cardiology Department, University Clinical Hospital Center Dr. Dragisa Misovic, Belgrade, Serbia and Faculty of Medicine, University of Belgrade, Belgrade, Serbia. 8. Department of Cardiology, Faculty of Medicine, University Hospital Medical Center Bezanijska kosa, University of Belgrade, Belgrade, Serbia. 9. Department of Cardiology and Department of Research and Education, General Hospital Celje, Celje, Slovenia; Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia. 10. Clinic for Cardiovascular Diseases, Clinical Center Nis, Serbia. 11. Clinical Hospital Center Zemun, Faculty of Medicine, University of Belgrade, Belgrade, Serbia. 12. Department of Cardiology, Charité Universitätsmedizin, Campus Virchow-Klinkum, Berlin, Germany; DZHK Partner Site Berlin, Berlin, Germany. Electronic address: hans-dirk.duengen@charite.de.
Abstract
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).
RCT Entities:
OBJECTIVES: This study evaluated the tolerability and feasibility of titration of 2 distinctly acting beta-blockers (BB) in elderly heart failurepatients 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 InsufficiencyBisoprolol 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).
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