Sodium-glucose cotransporter 2 inhibitor in heart failure patients and their outcomes: A meta-analysis of randomized controlled trials

Abstract

BACKGROUND

The use of sodium-glucose cotransporter 2 (SGLT2) inhibitor in heart failure (HF) patients is increasing significantly, regardless of whether they have a history of diabetes. The effects of SGLT2 inhibitor on HF are likely mediated through multiple mechanisms, including suppression of the renin-angiotensin-aldosterone system (RAAS), reduction in oxidative stress leading to enhanced myocardial efficiency, and attenuation of adverse cardiac remodeling by preventing fibrosis. These pathways are fundamental to reducing mortality, improving patients' quality of life, and alleviating the burden on the United States healthcare system by decreasing HF-related hospitalizations.

AIM

To evaluate SGLT2 inhibitor effects on HF, focusing on hospitalization for HF (HHF), cardiovascular (CV) deaths, and all-cause mortality.

METHODS

A comprehensive search was conducted in PubMed for randomized controlled trials (RCTs) evaluating the effects of SGLT2 inhibitor in HF patients compared to placebo, covering the period from January 1, 2014, to January 1, 2025. The primary outcomes assessed were HHF, CV deaths, and all-cause mortality. RevMan Web 5.4.1 was used to assess the risk of bias heterogeneity and to perform the statistical analyses. A random-effects model was employed for all statistical evaluations.

RESULTS

A total of nine RCTs were included in this analysis: DELIVER, DECLARE-TIMI 58, DAPA-HF, EMPA-REG OUTCOME, EMPEROR-Reduced, EMPEROR-Preserved, SOLOIST-WHF, EMPULSE, and VERTIS-CV. For HHF, eight trials (excluding the SOLOIST-WHF; n = 25906) were pooled, while CV deaths were assessed using data from eight trials (excluding the EMPULSE; n = 26598). Compared to placebo, SGLT2 inhibitor significantly reduced the risk of HHF (relative risk: 0.74; 95%CI: 0.71-0.77; P < 0.00001) and CV death (odds ratio: 0.88; 95%CI: 0.83-0.92; P = 0.0006). All nine trials (n = 27128) were included in the analysis of all-cause mortality. SGLT2 inhibitor were associated with a statistically significant reduction in all-cause mortality compared to placebo (OR: 0.91; 95%CI: 0.84-0.98; P = 0.02).

CONCLUSION

These results suggest that SGLT2 inhibitor significantly reduce the risk of hospitalization for HF, CV deaths, and all-cause mortality.

Keywords: Sodium-glucose cotransporter 2 inhibitor; Heart failure; Hospitalizations for heart failure; Cardiovascular deaths; All-cause mortality

Core Tip: Sodium-glucose cotransporter 2 (SGLT2) inhibitor have been incorporated into heart failure (HF) treatment guidelines due to their established benefits in patients with HF. They can be initiated in HF patients irrespective of their diabetes history. These medications significantly lower the risk of hospitalization for HF. SGLT2 inhibitor may also reduce cardiovascular deaths and all-cause mortality in HF patients, though the statistical significance of these outcomes has not been consistently demonstrated across all studies.