Key Points
- The DECODE-CKD trial investigated the effects of SGLT-2 inhibitor Dapagliflozin on cardiac structure and function in patients with chronic kidney disease (CKD).
- A double blinded, single centered, investigator initiated, placebo controlled randomized trial assessed cardiac structure and function in 222 patients over a period of 6 months.
- A significant reduction in the left ventricular mass index (LVMi) was noticed after 6 months of therapy, and consistent in all subgroups. A concomitant proportional dip in the estimated glomerular filtration rate (eGFR) was also noted.
An analysis of the primary and secondary endpoint results of the DECODE-CKD were presented at ACC2025 on Monday, March 31, 2025. CKD has been implicated time and again as the cause of cardiac remodeling and subsequent adverse cardiovascular outcomes in this population. This trial takes precedence from DAPA-CKD and EMPA-KIDNEY in relation to their findings of reduced adverse cardiovascular outcomes due to SGLT2 inhibitors. However, the favorable effects of SGLT2 inhibitors on cardiac structure and function are specifically studied in DECODE-CKD and present a rather interesting forecast.
The participants were included with a diagnosis of CKD, defined as having two measurements of an eGFR ml/min/1.73m2 between 20-60, or an eGFR ≥ 60 ml/min/1.73m2 with two urinary albumin-to-creatinine ratio (UACR) measurements of at least 200mg/g measured at least 3 months apart. Optimized patients taking renin angiotensin system inhibitors were also included. Patients with type 1 diabetes, kidney/heart transplants, SGLT2i use within 8 weeks and patients on dialysis were excluded from the study.
A total of 222 participants were randomized into Dapagliflozin group (110) and Placebo group (112). At the end of the trial, 104(94.5%) participants of Dapagliflozin group and 109 (97.3%) from Placebo group completed the study. The participants were monitored using blood samples and echocardiography on day 0 and within 10 days after completion of 6 months of study treatment.
At baseline, participants in the dapagliflozin group exhibited a higher prevalence of cardiovascular disease (40.0% vs. 28.6%) and greater use of renin-angiotensin system inhibitors (71.8% vs. 66.1%) compared to the placebo group. Additionally, fewer participants in this group had an estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73m² (14.5% vs. 21.4%). In terms of echocardiographic measures, they had a slightly larger left ventricular (LV) mass (163.3 ± 52.8 g vs. 154.1 ± 47.1 g) and LV mass index (80.3 ± 23.4 g/m² vs. 75.7 ± 20.0 g/m²), as well as a larger left atrial (LA) volume (52.6 ± 19.6 mL vs. 48.8 ± 17.6 mL) and volume index (25.1 ± 7.6 mL/m² vs. 23.3 ± 7.6 mL/m²). In contrast, the placebo group had a higher proportion of participants with an eGFR below 30 mL/min/1.73m² (21.4% vs. 14.5%). Their left ventricular ejection fraction (LVEF) was marginally higher (51.7 ± 8.5% vs. 50.3 ± 7.0%), and their E/A ratio suggested slightly better diastolic function (0.9 [0.8, 1.2] vs. 0.8 [0.6, 1.1]). While both groups had comparable overall characteristics, these differences highlight variations in baseline cardiovascular and renal function that may have influenced treatment outcomes.
The primary endpoint of LVMi was assessed in all enrolled patients. The secondary endpoints under consideration were left ventricular mass (LVM), left ventricular ejection fraction (LVEF), Global longitudinal strain (GLS), left ventricular end diastolic volume (LVEDV), left ventricular end systolic volume (LVESV), left atrial volume index (LAVI), eGFR, UACR, hemoglobin (Hb), pro BNP, and Troponin. Analysis of covariance was used to analyze the above parameters.
The population under study exhibited 80% power to detect a reduction of -8 g/m2 in LVMi when Dapagliflozin is administered for 6 months. A significant dip in eGFR was also noted to be proportional to the magnitude of LVMi regression.
Dr. Tor Biering-Sørensen, MD, MSc, MPH, PhD, and his research team at the University of Copenhagen report that their findings provide critical mechanistic insights into the cardioprotective effects of SGLT2 inhibitors in individuals with chronic kidney disease (CKD). Their study demonstrates that dapagliflozin significantly reduces left ventricular (LV) mass index to a greater extent than placebo following six months of therapy, highlighting its potential role in mitigating cardiac remodeling in this high-risk population.