Impact of Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2i) on Cardiovascular Outcomes in Heart Failure With Reduced Ejection Fraction Under Contemporary Standard Care: A Systematic Review and Meta-Analysis

This systematic literature review and meta-analysis evaluates the efficacy of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in reducing key cardiovascular outcomes, namely hospitalization for heart failure, cardiovascular mortality, and all-cause mortality in patients with heart failure with reduced ejection fraction (HFrEF). A total of 12 publications (including subgroup analyses) were analyzed. The selected RCTs compared the effects of SGLT2i (empagliflozin, dapagliflozin, and canagliflozin) with standard care among patients with HFrEF. The pooled data demonstrated that SGLT2i significantly reduced the risk of cardiovascular mortality by 23% and hospitalization for heart failure by 25%, compared to standard care. These benefits were consistently observed across both diabetic and non-diabetic subgroups, underscoring the broader therapeutic potential of SGLT2i in HFrEF management. However, no statistically significant reduction in all-cause mortality was identified. While the findings affirm the cardioprotective effects of SGLT2i, the lack of impact on overall mortality highlights the need for further longitudinal studies. These results support the integration of SGLT2i into contemporary HFrEF treatment protocols while informing future research priorities.