#6379 EFFECTS OF SODIUM-GLUCOSE CO-TRANSPORTER 2 INHIBITORS ON CARDIOVASCULAR MORTALITY INCHRONIC KIDNEY DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract

Abstract Background and Aims In studies of patients with chronic kidney disease (CKD), recommended nephroprotective therapy with ACE-inhibitors or ARBs has not been shown to reduce cardiovascular (CV) events or mortality. Sodium-glucose co-transporter 2 (SGLT-2) inhibitors reduce cardiovascular events and death in patients with diabetes and established CV disease; evidence from studies in populations with CKD has been inconsistent. The aim of this meta-analysis was to evaluate the effect of SGLT-2 inhibitors on cardiovascular (CV) mortality in patients with CKD. Method Studies were identified by search in major electronic databases (PubMed/MEDLINE, Scopus, Cochrane Library and Web of Science) (PROSPERO ID: CRD42022382863). We included randomized controlled trials assessing the effect of SGLT-2 inhibitors on the primary outcome, time to cardiovascular death, in patients with CKD at baseline. Secondary outcomes included all-cause mortality and major adverse cardiac events (MACE). Results Eleven studies with 83,203 participants with CKD were eligible for inclusion in the meta-analysis. Treatmentwith SGLT-2 inhibitors, compared to placebo, reduced the risk of CV death by 14% (hazard ratio [HR] 0.86;95%CI 0.79-0.94), of all-cause death by 15% (HR 0.85; 95%CI 0.79-0.91) and of MACE by 13% (HR 0.87; 95%CI0.81-0.93). A consistent treatment effect on the primary outcome was observed with all SGLT-2 inhibitors(canagliflozin: HR 0.84; 95%CI 0.69-1.02, dapagliflozin: HR 0.89; 95%CI 0.78-1.01, empagliflozin: HR 0.82;95%CI 0.69-0.97 sotagliflozin: HR 0.90; 95%CI 0.73-1.12) studied (p-subgroup-differences = 0.85). Sensitivity analysis pooling data from studies including only diabetic patients with CKD yielded similar results (HR 0.86;95%CI 0.77-0.97). Conclusion Treatment with SGLT-2 inhibitors led to a significant reduction in the risk for CV and all-cause mortality in CKD patients. These findings support the use of these agents also for protection against cardiovascular events and death in CKD.