Katja Vu Bartholdy, Niklas Dyrby Johansen, Kristoffer Grundtvig Skaarup, Daniel Modin, Nino Emanuel Landler, Adam Cadovius Femerling Langhoff, Camilla Ikast Ottosen, Caroline Espersen, Maria Dons, Julie Borchsenius, Lise Witten Davodian, Mats Christian Højbjerg Lassen, Filip Soeskov Davidovski, Anne Marie Reimer Jensen, Morten Sengeløv, Jacob Christensen, Morten Schou, Bo Feldt‐Rasmussen, J. Steen Jensen, Iain Bressendorff, Frederik Persson, Peter Rossing, Lars Køber, Faı̈ez Zannad, Muthiah Vaduganathan, Scott D. Solomon, Richard Haynes, Ditte Hansen, Tor Biering‐Sørensen
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: 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: (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.).