Effects of sodium-glucose co-transporter 2 inhibitors on heart failure events in chronic kidney disease: a systematic review and meta-analysis

Abstract

Aims: Sodium-glucose co-transporter 2 (SGLT-2) inhibitors significantly reduce the risk for hospitalizations for heart failure (HF) in patients with diabetes, and HF; findings in patients with chronic kidney disease (CKD) are not uniform. We aimed to perform a meta-analysis exploring the effect of SGLT-2 inhibitors on HF events in patients with CKD and across subgroups defined by baseline kidney function.

Methods and results: A systematic search in major electronic databases was performed. Randomized controlled trials (RCTs) providing data on the effect of SGLT-2 inhibitors on the primary outcome, time to hospitalization or urgent visit for worsening HF in patients with prevalent CKD at baseline or across subgroups stratified by baseline estimated glomerular-filtration-rate (eGFR) were included. Twelve studies (n = 89,191 participants) were included in the meta-analysis. In patients with CKD, treatment with SGLT-2 inhibitors reduced the risk for HF events by 32% compared to placebo [hazard ratio (HR) 0.68; 95% confidence interval (CI) 0.63-0.73]. Reduction in HF events with SGLT-2 inhibitors was more prominent in patients with eGFR <60 ml/min/1.73 m2 (HR 0.68; 95% CI 0.62-0.74) than in those with eGFR ≥60 ml/min/1.73 m2 (HR 0.76; 95% CI 0.69-0.83). Subgroup analysis according to type of SGLT-2 inhibitor showed a consistent treatment effect across all studied agents (p-subgroup-analysis = 0.44). Sensitivity analysis including data from studies including only diabetic patients showed an even more pronounced effect in eGFR subgroup <60 ml/min/1.73 m2 (HR 0.62; 95% CI 0.54-0.70).

Conclusion: Treatment with SGLT-2 inhibitors led to a significant reduction in HF events in patients with CKD. Such findings may change the landscape of prevention of HF events in patients with advanced CKD. PROSPERO Registration number CRD42022382857.

Keywords: Chronic kidney disease; Heart failure; Hospitalization for heart failure; SGLT-2 inhibitors.