Dapagliflozin safely reduces kidney failure risk, cardiovascular mortality in advanced CKD
An analysis of DAPA-CKD data showed dapagliflozin reduces the risk for kidney failure and mortality in patients with advanced chronic kidney disease, a subgroup that made up 14% of the study population included in the initial trial.
Further, researchers deemed the drug safe after observing no increased risk for serious adverse events when compared with patients who had less severe stages of chronic kidney disease.
“This analysis shows that the effects of dapagliflozin in patients with stage 4 CKD are similar to effects in patients with mild to moderate CKD,” Glenn M. Chertow, MD, MPH, of Stanford University School of Medicine, said in a related press release. “While patients with screening eGFR as low as 25 mL/min/1.73 m2 were enrolled, it is noteworthy that neither dapagliflozin nor placebo were discontinued when eGFR declined, even to below 15 mL/min/1.73 m2. Therefore, a drug initially developed for the treatment of diabetes can benefit patients with CKD with and without diabetes, including patients with moderate to advanced CKD.”
A total of 624 patients with advanced CKD, defined as eGFR less than 30 mL/min/1.73 m2, were randomized to 10 mg per day of the SGLT2 inhibitor dapagliflozin or placebo, with researchers considering a composite of sustained decline in eGFR of at least 50%, end-stage kidney disease or kidney or cardiovascular mortality as the primary outcome. Secondary outcomes included a kidney composite – defined as a sustained decline in eGFR of at least 50%, development of ESKD or mortality due to kidney disease – a composite of cardiovascular death or heart failure hospitalization and all-cause mortality.
Dapagliflozin vs placebo for advanced CKD
Results showed that, compared with placebo, treatment with dapagliflozin led to a 27% reduction in the primary composite endpoint, while also reducing the risk for the kidney composite endpoint by 29%, the cardiovascular composite endpoint by 17% and the all-cause mortality endpoint by 32%.
Further findings indicated that those randomized to dapagliflozin has a slower annual decline in eGFR slope compared with placebo (decline of 2.15 mL/min/1.73 m2 per year vs. 3.38 mL/min/1.73 m2).
Adverse events, drug safety
Rates of serious adverse events and adverse events of “special interest” (which included symptoms of volume depletion, kidney-related events, major hypoglycemia, bone fractures, amputations and potential diabetic ketoacidosis) were similar among patients treated with dapagliflozin or placebo.
“While kidney-related AEs were observed more frequently in patients with stage 4 CKD at baseline, neither the proportion of patients (15% vs. 13%) nor the relative odds of experiencing kidney-related AEs (1.12) were significantly increased in patients randomized to dapagliflozin,” the researchers determined when evaluating risks for patients with advanced CKD compared with the overall study population.
“[A]mong patients with stage 4 CKD and albuminuria, with and without type 2 diabetes, the effects of dapagliflozin on reducing the risks of major kidney and cardiovascular events and attenuating progressive loss of eGFR are consistent with those observed in the trial overall, with no evidence of increased risks,” Chertow and colleagues concluded. “Dapagliflozin should be considered part of the therapeutic armamentarium for patients with stage 4 CKD and albuminuria.”