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Assessment of Vascular Function in Patients With Chronic Kidney Disease
Published on: June 16, 2014
Cardiac Effects of Dapagliflozin in People with Chronic Kidney Disease
Katja Vu Bartholdy1,2,3, Niklas Dyrby Johansen1,2,3, Kristoffer Grundtvig Skaarup1,2,3
1Center for Translational Cardiology and Pragmatic Randomized Trials, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen.
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.).
Insights
Sodium-glucose cotransporter 2 (SGLT2) inhibitors like dapagliflozin significantly reduce left ventricular mass index in patients with chronic kidney disease. This trial offers insights into the cardioprotective mechanisms of SGLT2 inhibitors for kidney disease patients.
Area of Science:
- Cardiology
- Nephrology
- Pharmacology
Background:
- Adverse cardiac remodeling is a significant concern in chronic kidney disease (CKD), increasing cardiovascular risk.
- Sodium-glucose cotransporter 2 (SGLT2) inhibitors demonstrate cardioprotective effects in CKD patients, but mechanisms require further elucidation.
- This study investigates the impact of SGLT2 inhibitors on cardiac structure and function in individuals with CKD.
Purpose of the Study:
- To evaluate the effect of dapagliflozin on cardiac structure and function in patients with chronic kidney disease.
- To explore the mechanistic insights into the cardioprotective benefits of SGLT2 inhibitors in the context of CKD.
Main Methods:
- The Effects of Dapagliflozin on EChOcardiographic Measures of CarDiac StructurE and Function in Patients with Chronic Kidney Disease (DECODE-CKD) trial was a 6-month, randomized, double-blind, single-center study.
- Participants with CKD (eGFR 20-59 or ≥60 ml/min/1.73 m2 with UACR ≥200 mg/g) received either dapagliflozin or placebo.
- Primary endpoint: change in left ventricular mass index; secondary endpoints included cardiac function, troponin I, pro-BNP, hemoglobin, UACR, and creatinine.
Main Results:
- A total of 222 patients were randomized; mean age 67.5 years, 29.3% women, with significant prevalence of cardiovascular disease (34.2%), hypertension (75.7%), and CKD etiologies like hypertensive nephropathy (25.7%).
- Dapagliflozin significantly reduced left ventricular mass index by -8.44 g/m2 compared to placebo (95% CI, -11.83 to -5.06; P<0.001).
- Treatment effects were consistent across subgroups, and serious adverse event rates were similar between dapagliflozin and placebo groups.
Conclusions:
- Dapagliflozin significantly decreased left ventricular mass index in a diverse CKD population, suggesting a direct impact on cardiac remodeling.
- These findings provide mechanistic evidence supporting the early cardioprotective benefits of SGLT2 inhibitors observed in prior CKD studies.
- Further research is warranted to confirm and refine the understanding of these early treatment benefits of SGLT2 inhibitors in CKD.
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