Sodium-glucose co-transporter 2 inhibitors in heart failure with mildly reduced or preserved ejection fraction: an updated systematic review and meta-analysis

OBJECTIVES: Heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with preserved ejection fraction (HFpEF) are associated with significant morbidity and mortality, as well as growing health and economic burden. Sodium-glucose co-transporter 2 (SGLT2) inhibitors are very promising for the outcome improvement of patients with HFpEF or HFmrEF. The meta-analysis was performed to investigate the effects of SGLT2 inhibitors in HFpEF or HFmrEF, by pooling data from all clinically randomized controlled trials (RCTs) available to increase power to testify. METHODS: Studies were searched in electronic databases from inception to November, 2022. We performed a meta-analysis to estimate the effect of SGLT2 inhibitors on clinical endpoints in patients with HFpEF or HFmrEF, using trial-level data with consistent endpoint definitions. The primary outcome was the composite of heart failure (HF) hospitalization or cardiovascular death. Hazard ratio (HR) was pooled with 95% confidence interval (CI) for dichotomous data. This study was registered with INPLASY 2022110095. RESULTS: Six studies involving 15,989 participants were included into the final analysis. Pooled analyses revealed that SGLT2 inhibitors significantly reduced the composite of HF hospitalization or cardiovascular death [HR: 0.79 (0.72–0.85); I(2) = 0%; P < 0.00001] and HF hospitalizations [HR: 0.74 (0.67–0.82); I(2) = 0%; P < 0.00001]. This finding was seen in both HFmrEF trials [HR: 0.76 (0.67–0.87); I(2) = 49%; P < 0.0001] and HFpEF subgroup studies [HR: 0.70 (0.53–0.93); I(2) = 0%; P = 0.01]. The incidence of any serious adverse events [OR: 0.89 (0.83–0.96); I(2) = 0%; P = 0.002] was significantly lower in the SGLT2 inhibitor arm. No significant differences were observed between the two groups with regard to cardiovascular death and all-cause death. CONCLUSIONS: This meta-analysis of patients with heart failure of left ventricular ejection fraction (LVEF) > 40% showed that SGLT2 inhibitors significantly reduce the risk of the composite of cardiovascular death and hospitalization for heart failure, but not cardiovascular death and all-cause death. Nevertheless, given that SGLT2 inhibitors may reduce the risk of hospitalization for heart failure, they should be considered the fundamental treatment for all patients with HFpEF or HFmrEF. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40001-022-00945-z.