Real-world effectiveness of SGLT2 inhibitors in patients with HF and ESKD: a multicenter cohort study

Background: Patients with heart failure (HF) and end-stage kidney disease (ESKD) face a high burden of mortality and hospitalization, yet effective therapeutic options remain limited. While sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated cardiovascular and renal benefits across various chronic kidney disease (CKD) stages, their effects in patients with HF and ESKD remain uncertain due to their exclusion from major clinical trials. Objectives: This study aimed to evaluate the effectiveness of SGLT2i in reducing one-year clinical outcomes, including all-cause hospitalization, all-cause mortality, and acute pulmonary edema in patients with HF and ESKD. Methods: A retrospective cohort study was conducted using the TriNetX network. Patients with HF and ESKD diagnosed between 2016 and 2025 were identified and categorized into SGLT2i users and non-users. The primary outcome was a composite of all-cause hospitalization, all-cause mortality, and acute pulmonary edema at 1 year. Secondary outcomes included each component of the primary composite. Propensity score matching (PSM) was applied to balance baseline characteristics. Cox proportional hazard models estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for primary and secondary outcomes. Sensitivity analyses, including negative control and landmark analyses, were performed to validate findings. Results: < 0.001). Subgroup analyses demonstrated consistent benefits across different HF phenotypes, comorbidities, and different types of SGLT2i. Conclusions: SGLT2i are significantly associated with reduced 1 year all-cause hospitalization, mortality, and acute pulmonary edema in HF and ESKD patients. These findings highlight the potential therapeutic role of SGLT2i in this high-risk population, warranting further clinical trials to confirm their efficacy and safety.