Sodium-glucose cotransporter type 2 inhibitors in patients with heart failure with preserved ejection fraction: a systematic review and meta-analysis

Background. Epidemiological studies show that mortality among patients with heart failure and preserved left ventricular ejection fraction remains high. In recent clinical studies, inhibitors of sodium-glucose cotransporter type 2 are showing promise in reducing cardiovascular complications in patients with chronic heart failure who need effective drug treatment.

Aim. We aimed to analyze published randomized controlled clinical trials evaluating the effectiveness of sodium-glucose cotransporter type 2 inhibitors, added to standard therapy, in a group of patients with chronic heart failure and a left ventricular ejection fraction over 40%.

Materials and methods. A systematic review and meta-analysis of the scientific literature were performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A literature search of the PubMed database for the period from January 2021 to December 2022 was performed. The search keywords included the following MeSH terms: “heart failure preserved ejection fraction” or “HFpEF” and “empagliflozin” or “dapagliflozin” or “SGLT2.” The search did not use filters for language or type of study. All statistical analyses were performed using the RevMan version 5.4 (Copenhagen, the Nordic Cochrane Centre, The Cochrane Collaboration, 2014).

Results. The initial search retrieved 481 publications. After further screening and exclusions for non-compliance with the inclusion criteria, two clinical studies were included. There were 12 251 patients in total, 6128 received sodium-glucose cotransporter type 2 inhibitors, 6123 received placebo. Patients treated with these drugs were 20% less likely to have a combined endpoint (odds ratio [OR] 0.80, 95% confidence interval [CI] 0.72–0.87; p <0.001). This was primarily due to a 26% decrease in the frequency of hospitalization for acute decompensation of heart failure (OR 0.74, 95% CI 0.66–0.83; p <0.001). There was a trend toward decreased mortality from cardiovascular causes (OR 0.88, 95% CI 0.77–1.01; p=0.06), while no effect was observed on all-cause mortality (OR 0.96, 95% CI 0.87–1.06; p=0.38).

Conclusions. The meta-analysis shows the potential of sodium-glucose cotransporter type 2 inhibitors to reduce hospitalization for acute decompensation of heart failure in patients with a moderately reduced and preserved left ventricular ejection fraction.