Prevention of new-onset heart failure and renoprotective effect with sodium-glucose cotransporter 2 inhibitors in patients with chronic kidney disease

Abstract Background In patients with chronic kidney disease (CKD), cardiorenal interaction may lead to the new onset of heart failure (HF) as well as further worsening of renal function. Angiotensin II receptor blockers (ARBs) have been widely used in CKD patients for both HF prevention and kidney protection. The effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2is) has not been fully elucidated in comparison to ARBs. Purpose This study aimed to compare SGLT2is with ARBs in terms of the prevention of new-onset HF and the preservation of glomerular filtration rate (GFR) in patients with CKD, using real-world global electronic medical records. Methods Using the real-world global electronic medical record TriNetX database, we conducted a retrospective cohort study of patients with CKD and no history of HF. Patients with an estimated GFR (eGFR) of 15–60 mL/min/1.73m², no prior HF diagnosis, and no elevation in B-type natriuretic peptide (BNP) or N-terminal proBNP were included. Those who newly initiated either dapagliflozin or ARBs between 2020 and 2023 were identified and analyzed. Patients who were treated with angiotensin-converting enzyme inhibitors were excluded. The primary outcome was a composite of all-cause death, new-onset HF, eGFR decline to 15 mL/min/1.73m², or hemodialysis (HD). Each component of these outcomes was also analyzed. Propensity-score matching (PSM) was used to adjust for baseline characteristics. Results After PSM, 4,817 of 5,046 patients in the dapagliflozin group were matched to 4,817 of 122,831 patients in the ARBs group. The dapagliflozin group was associated with a lower incidence of the primary composite endpoint than the ARBs group (8.6% vs. 11.6%, hazard ratio HR 0.72, 95% confidence interval CI 0.64–0.82, p 0.001, Figure). The composite of all-cause death or new-onset HF and the composite of eGFR decline to 15 mL/min/1.73m² or HD were also less frequently observed in the dapagliflozin group. Findings were consistent regardless of the history of diabetes mellitus and across different values of urinary albumin-creatinine ratio. Conclusion Dapagliflozin may be more beneficial than ARBs in preventing the development of new-onset HF and worsening of renal function in patients with CKD.Figure