Sodium–glucose cotransporter 2 inhibitors in heart failure with preserved ejection fraction: A protocol for meta-analysis

BACKGROUND: Nearly half of patients with heart failure (HF) have preserved ejection fraction (EF) and the mortality and morbidity of patients with HF with preserved EF (HFpEF) are high. Patients with HFpEF are often elderly and their primary chronic symptom is severe exercise intolerance that results in a reduced quality of life. Thus, improvement of exercise capacity presents another important clinical outcome in HFpEF patients. Recent randomized controlled trials (RCTs) and meta-analyses of RCTs reported that sodium–glucose cotransporter 2 (SGLT-2) inhibitors improved cardiovascular outcomes in patients with HF with reduced EF. Although the effects of SGLT-2 inhibitors in HFpEF patients have been examined in multiple RCTs, the results are inconsistent due partly to limited power. The purpose of this meta-analysis is to evaluate the efficacy and safety of SGLT-2 inhibitors in HFpEF patients. METHODS: This meta-analysis will include RCTs examining the effects of SGLT-2 inhibitors on HF severity and health-related quality of life in HFpEF patients. Information of studies will be collected from electronic databases. The primary outcome will be HF severity (plasma B-type natriuretic peptide levels and exercise capacity assessed as 6-minute walk distance). The secondary outcome will be health-related quality of life. The safety outcomes will be all-cause death, HF hospitalization, hypotension, acute renal failure, diabetic ketoacidosis, and urinary tract infection. DISCUSSION: This meta-analysis will evaluate the efficacy and safety of SGLT-2 inhibitors in HFpEF patients, providing evidence to the clinical use of SGLT-2 inhibitors in these patients. SYSTEMATIC REVIEW REGISTRATION: INPLASY2021120033