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Tolerability and Feasibility of Beta-Blocker Titration in HFpEF Versus HFrEF: Insights From the CIBIS-ELD Trial
Frank Edelmann1, Lindy Musial-Bright2, Goetz Gelbrich3
1Department 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.
Insights
Beta-blockers (BB) showed comparable tolerability in elderly patients with heart failure with reduced (HFrEF) or preserved ejection fraction (HFpEF). While both groups experienced heart rate and blood pressure reductions, only HFrEF patients showed significant clinical improvements.
Area of Science:
- Cardiology
- Geriatrics
- Pharmacology
Background:
- Evidence supports beta-blocker (BB) use in heart failure with reduced ejection fraction (HFrEF).
- The efficacy of BB in heart failure with preserved ejection fraction (HFpEF) remains uncertain.
- Elderly patients represent a significant population with heart failure, necessitating tailored treatment evaluations.
Purpose of the Study:
- To evaluate the tolerability and feasibility of titrating two distinct beta-blockers (bisoprolol and carvedilol) in elderly patients with HFpEF and HFrEF.
- To compare the clinical effects of beta-blockade between elderly HFrEF and HFpEF populations.
Main Methods:
- The CIBIS-ELD trial randomized over 65 years old patients with HFrEF (n=626) or HFpEF (n=250) to bisoprolol or carvedilol.
- Both BBs were up-titrated to the maximum tolerated dose, with follow-up at 12 weeks.
- Comparisons focused on tolerability, heart rate, blood pressure, cardiac function, functional class, exercise capacity, quality of life, and natriuretic peptide levels.
Main Results:
- Tolerability and achieved doses of BBs were similar between HFrEF and HFpEF groups.
- HFpEF patients experienced more dose escalation delays and treatment side effects.
- Both groups showed similar heart rate reductions, but only HFrEF patients demonstrated significant improvements in New York Heart Association functional class and left ventricular function.
Conclusions:
- Beta-blocker therapy is comparably tolerated in elderly HFrEF and HFpEF patients.
- While BBs reduce heart rate and blood pressure in both groups, clinical benefits are more pronounced in HFrEF.
- Current evidence does not support BBs for improving diastolic function markers in HFpEF; further research is needed.
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).
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