In patients with chronic kidney disease (CKD), with or without type 2 diabetes (T2D), dapagliflozin was shown to reduce the risk of kidney failure, death from cardiovascular causes or heart failure (HF) hospitalization and to prolong survival in patients whether or not they had HF at baseline. The new findings from a prespecified analysis of the DAPA-CKD trial will be presented during ESC Congress 2021 and were published Aug. 23 in JACC: Heart Failure.

Among the 4,304 patients randomized in DAPA-CKD, John J.V. McMurray, MD, FACC, et al., evaluated the effects of dapagliflozin 10 mg once daily by presence (n=468; 11%) or absence (n=3,836; 89%) of HF at baseline. Patients with HF, compared with those without, were older (65.3 vs. 61.4 years), more frequently White (80.1% vs. 49.9%), had a higher body mass index (31.7 kg/m² vs. 29.2 kg/m²), and were more likely to have obesity and T2D (77.1% vs. 66.3%). Mean estimated glomerular filtration rate (eGFR) and median urinary albumin-to-creatinine ratio (UACR) were similar in patients with and without baseline HF. To be eligible for study enrollment, patients had an eGFR between 25-75 mL/min/1.73 m² and an UACR between 200-5,000 mg/g.

Results showed a similar reduction with dapagliflozin in the risk of the primary composite outcome of a ≥50% decline in eGFR, end-stage kidney disease or kidney/cardiovascular death in patients with HF (HR, 0.58; 95% confidence interval [CI], 0.37-0.91) and without HF (HR, 0.62; 95% CI, 0.51-0.75; p for interaction=0.59). In patients with and without HF at baseline, the rate for the primary outcome was 8.7 per 100 person-years vs. 5.7 per 100 person-years (HR, 1.48; 95% CI, 1.17-1.88; p=0.0019); the higher rate in patients with HF was driven by a higher rate of cardiovascular death (4.3 vs. 1.2 per 100 person-years, vs. without HF; HR, 3.31; p<0.0001).

Looking at secondary endpoints, the rates of HF hospitalization/cardiovascular death and all-cause death were higher in HF patients, but the secondary kidney failure outcome occurred at the same rate in patients with and without HF. The proportional risk reductions were similar in patients with and without HF for the cardiovascular death/HF hospitalization composite (HR, 0.68 vs. HR, 0.70; p for interaction=0.90) and for all-cause death (HR, 0.56 vs. HR, 0.73; p for interaction=0.39); absolute risk reductions were larger in HF patients.

The authors note that the effect of SGLT2 inhibitors on the primary and secondary prevention of HF in patients with CKD plus or minus T2D has not been studied. They conclude that dapagliflozin was equally effective in preventing incident HF hospitalization and in preventing kidney failure and all-cause death whether or not patients had HF at baseline.

Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure

Keywords: ESC Congress, ESC21, Creatinine, Glomerular Filtration Rate, Diabetes Mellitus, Type 2, Body Mass Index, Glucosides, Benzhydryl Compounds, Heart Failure, Renal Insufficiency, Chronic, Hospitalization, Kidney, Kidney Failure, Chronic, Obesity, Albumins

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