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Effect of beta-blockers on heart failure severity in patients with heart failure with preserved ejection fraction: a meta-analysis of randomized controlled trials

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Abstract

Patients with heart failure with preserved ejection fraction (HFpEF) are often elderly and likely to have cardiac comorbidities such as coronary artery disease (CAD) and atrial fibrillation (AF). The primary chronic symptom of HFpEF patients is severe exercise intolerance. The inability to adequately increase heart rate during exercise is commonly present in HFpEF patients and contributes to their exercise intolerance. Although beta-blockers are frequently used for the treatment of myocardial ischemia and tachycardia in HFpEF patients, there is a concern that slowing heart rate by beta-blockers may worsen chronotropic incompetence and further exacerbate their symptoms. Although the effect of beta-blockers on heart failure severity in HFpEF patients has been examined in randomized controlled trials (RCTs), results are inconsistent due partly to limited power. We aimed to conduct a meta-analysis of RCTs on the effect of beta-blockers on heart failure severity in HFpEF patients. The search of electronic databases identified 5 RCTs including 538 patients. In pooled analyses, beta-blockers did not significantly change the New York Heart Association (NYHA) class, exercise capacity expressed as metabolic equivalents, or plasma B-type natriuretic peptide (BNP) levels compared with control but with substantial heterogeneity across trials. In meta-regression analyses, the higher proportion of CAD or AF in the included trials was associated with a decrease in NYHA class and BNP levels and with an increase in exercise capacity. Thus, we found no clear beneficial effect of beta-blockers on heart failure severity in HFpEF patients. However, beta-blockers may be beneficial in HFpEF patients with CAD or AF.

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Correspondence to Hidekatsu Fukuta.

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Conflict of interest

Dr. Ohte has received lecture fees from the Daiichi Sankyo Co. and grant support from the Takeda Pharmaceutical Co. Ltd., Daiichi Sankyo Co., Ltd., and Otsuka Pharmaceutical Co., Ltd. Dr. Kamiya has received lecture fees from the Astellas Pharma Inc. and Mochida Pharmaceutical Co., Ltd.

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Supplement Fig. 1

Forest plots showing the effects of beta-blockers (BBs) on heart rate (bpm; a), left ventricular (LV) mass (g; b), left atrial (LA) dimension (mm, c), ejection fraction (EF; %, d), the ratio of peak early to late diastolic mitral inflow velocities (E/A; e), and the ratio of early diastolic mitral inflow to annular velocities (E/e’; f). (PPTX 47 kb)

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Fukuta, H., Goto, T., Wakami, K. et al. Effect of beta-blockers on heart failure severity in patients with heart failure with preserved ejection fraction: a meta-analysis of randomized controlled trials. Heart Fail Rev 26, 165–171 (2021). https://doi.org/10.1007/s10741-020-10013-5

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