Effects of beta-blocker withdrawal in patients with heart failure with preserved ejection fraction: A protocol for systematic review and meta-analysis

Background: The primary chronic symptom of patients with heart failure with preserved ejection fraction (HFpEF) is severe exercise intolerance. The inability to adequately increase heart rate during exercise (chronotropic incompetence) is commonly present in HFpEF patients and contributes importantly to exercise intolerance in these patients. Since HFpEF patients often have cardiac comorbidities such as hypertension, coronary artery disease, and atrial fibrillation, beta-blockers are frequently prescribed for the treatment of these comorbidities. However, there is a concern that beta-blockers may worsen chronotropic incompetence by slowing heart rate in HFpEF patients and may further exacerbate their symptoms. There are several studies on the effects of beta-blocker withdrawal in HFpEF patients. We aim to perform the systematic review and meta-analysis of studies on the effects of beta-blocker withdrawal in HFpEF patients. Methods: This meta-analysis will include randomized controlled trials and prospective cohort studies on the effect of beta-blocker withdrawal in HFpEF patients. Information of studies will be collected from PubMed, Web of Science, and Scopus. The primary outcome will be peak oxygen uptake (peak VO2). The secondary outcome will be 6-minute walk distance. Other outcomes of interest will be health-related quality of life, plasma BNP levels, and cardiac structure and function. Discussion: This systematic review and meta-analysis will evaluate whether beta-blocker withdrawal is beneficial for HFpEF patients, providing evidence regarding beta-blocker withdrawal in these patients. Trial registration: Systematic review registration: INPLASY202370066.