Cardiac Effects of Dapagliflozin in People with Chronic Kidney Disease.
Bartholdy KV., Johansen ND., Skaarup KG., Modin D., Landler N., Langhoff AF., Ottosen CI., Espersen C., Dons M., Borchsenius JIM., Davodian LW., Lassen MH., Davidovski FS., Jensen AMR., Sengeløv M., Christensen J., Schou M., Feldt-Rasmussen B., Jensen J., Bressendorff I., Persson F., Rossing P., Køber L., Zannad F., Vaduganathan M., Solomon S., Haynes R., Hansen D., Biering-Sørensen T.
BACKGROUND: Adverse cardiac remodeling is common in people with chronic kidney disease and contributes to increased cardiovascular risk. Although sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown cardioprotective effects in patients with chronic kidney disease, the underlying mechanisms are still not completely understood. This trial evaluated the impact of SGLT2 inhibitors on cardiac structure and function in patients with chronic kidney disease. METHODS: Effects of Dapagliflozin on EChOcardiographic Measures of CarDiac StructurE and Function in Patients with Chronic Kidney Disease (DECODE-CKD) was a 6-month, single-center, randomized, double-blind trial comparing dapagliflozin with placebo in patients with an estimated glomerular filtration rate of 20 to 59 or greater than or equal to 60 ml/minute/1.73 m2 with a urine albumin-creatinine ratio greater than or equal to 200 mg/g. Participants underwent serial echocardiography and biomarker assessment. The primary end point was the change in left ventricular mass index. Secondary end points included changes in systolic and diastolic function, high-sensitivity troponin I, pro-B-type natriuretic peptides, hemoglobin, the urine albumin-creatinine ratio, and creatinine. RESULTS: Of 268 screened individuals, 222 were randomly assigned. The mean age was 67.5 years; 29.3% were women. Cardiovascular disease was present at enrollment in 34.2%, heart failure in 5.9%, hypertension in 75.7%, and diabetes in 8.6%. The most common causes of chronic kidney disease were hypertensive nephropathy (25.7%) and polycystic kidney disease (16.7%). The estimated mean difference in left ventricular mass index between the dapagliflozin group compared with placebo was -8.44 g/m2 (95% confidence interval, -11.83 to -5.06; P<0.001). Effects were consistent across key subgroups, including by demographics, cardiovascular history, biomarkers, and chronic kidney disease etiology. The rate of serious adverse events was similar between the groups. CONCLUSIONS: In a heterogeneous population of patients with chronic kidney disease, dapagliflozin significantly reduced left ventricular mass index compared with placebo. These findings provide mechanistic insights into the early treatment benefits of SGLT2 inhibitors seen previously in chronic kidney disease. Further research is needed to replicate and further define these early treatment benefits. (Funded by the Danish Cardiovascular Academy and Novo Nordisk Foundation; ClinicalTrials.gov number, NCT05359263.).