Abstract

Introduction: Through an unknown mechanism, anti-diabetic sodium-glucose cotransporter-2 inhibitors have been shown to be effective in patients with heart failure reduced ejection fraction (HFrEF). Specifically, dapagliflozin significantly decreased the risk of cardiovascular death and hospitalization for heart failure. However, the effects on left ventricular remodeling have not been well reported or analyzed. Methods/Results: We conducted a meta-analysis of all randomized controlled trials that reported left ventricular remodeling outcomes in patients with HFrEF comparing dapagliflozin versus placebo. The outcomes in this study were analyzed as changes in values compared to baseline levels. Statistical analysis was conducted using Review Manager 5.4. Two-sided p values of <0.05 were considered as statistical significance. A total of 254 patients with a median-weighted follow-up duration of 13.13 months were included amongst four RCTs. Heterogeneity was low-high across the trials (0-85%). Stroke volume significantly favored the dapagliflozin arm (mean difference 1.85, 95% confidence interval 0.10 to 3.60, p=0.04, I 2 =0%). However, left ventricular mass index, left atrial volume index, left ventricular end systolic volume, left ventricular end diastolic volume, and E/e’ were determined to be insignificant between the dapagliflozin and placebo arms. The first outcome was assessed by cardiac magnetic resonance imaging, while the former were seen on echocardiograms. Conclusion: This meta-analysis illustrates that dapagliflozin significantly increased SV in HFrEF patients, but had an insignificant effect in the other left ventricular remodeling outcomes. One limitation of this meta-analysis is low power due to only a few trials in the literature. Therefore, further trials with larger sample size and longer follow-up periods should be conducted to determine the dapagliflozin’s outcome on left ventricular remodeling in patients with HFrEF.

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