Abstract

Heart failure (HF) and chronic kidney disease (CKD) often coexist, driving a maladaptive cardiorenal syndrome with high morbidity and mortality. A systematic review was conducted following PRISMA 2020 guidelines, searching PUBMED, Web of Science, Wiley Online Library, and ScienceDirect databases for studies (2015-2025) of SGLT2 inhibitors and related agents in adults with HF and CKD. Randomized trials and cohort analyses were included if they reported cardiovascular (CV) or renal outcomes. Data on study design, interventions, sample size, outcomes, and safety were extracted and appraised for bias. Across 11 trials (n = 34,999), SGLT2 inhibitors consistently reduced heart failure hospitalizations and CV death by 25-35%, slowed eGFR decline, and showed low rates of acute kidney injury. The subgroup analyses confirmed benefits in preserved and reduced ejection fraction and in CKD stages 2-4. Nonsteroidal MRA finerenone added further event reduction irrespective of SGLT2 background. These findings support SGLT2 inhibition as a cornerstone therapy in cardiorenal syndrome, though optimal initiation timing and combination regimens require further study.

Key words: SGLT2 inhibitors, dapagliflozin, empagliflozin, heart failure, chronic kidney disease, systematic review