December 15, 2015Open Access
View Full PaperTolerability and Feasibility of Beta-Blocker Titration in HFpEF Versus HFrEF
Key Result
Beta-blocker titration in elderly heart failure patients resulted in greater improvement in NYHA functional class for HFrEF compared to HFpEF (34% vs. 23%, p<0.001), despite similar heart rate reductions.
Study Design
Type
RCT (n=876)
Blinding
Double-blind
Randomization
randomized
Multicenter
Yes
Structured PICO
Does beta-blocker titration have similar tolerability and clinical effects in elderly patients with HFpEF compared to HFrEF?
P
Population
876 elderly patients (>65 years) with HFrEF or HFpEF, followed for 12 weeks to evaluate the tolerability and clinical effects of beta-blocker titration.
I
Intervention
Beta-blocker (bisoprolol or carvedilol) up-titrated to target or maximum tolerated dose in HFpEF patients
C
Comparator
Beta-blocker (bisoprolol or carvedilol) up-titrated to target or maximum tolerated dose in HFrEF patients
O
Outcome
Tolerability and feasibility of titration at 12 weekssafety
Beta-blocker titration is similarly tolerated in elderly HFpEF and HFrEF patients, but significant clinical improvements and left ventricular function benefits are predominantly seen in HFrEF.
Main Result
Absolute Event Rate: 23% vs 34%
p-value: p=<0.001
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).