Dapagliflozin slows kidney function decline and reduces mortality in patients with chronic kidney disease (CKD) with or without type 2 diabetes when added to standard of care, according to topline results from the international Dapagliflozin And Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD) trial reported at the European Society of Cardiology virtual congress.
In the phase 3 trial, investigators randomly assigned 4304 patients (mean age 62 years; 33% female) from 21 countries to receive dapagliflozin (10 mg once daily), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, or placebo in addition to standard of care. At baseline, patients had an estimated glomerular filtration rate (eGFR) of 25 to 75 mL/min/1.73 m2 and a urinary albumin to creatinine ratio (UACR) of 200 to 5000 mg/g. In addition, 97% were receiving a stable, maximum-tolerated dose of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB) for at least 4 weeks. Two-thirds had type 2 diabetes. By design, no participants could have type 1 diabetes, polycystic disease, lupus nephritis, ANCA-associated vasculitis, or recent immunosuppressant therapy. The racial composition of the cohort was 53% White, 34% Asian, 4.5% Black, and 8% other.
Hiddo Heerspink, PharmD, PhD, of the University Medical Center Groningen in Groningen, the Netherlands, and co-chair of the DAPA-CKD trial, reported that dapagliflozin reduced the primary composite outcome of a 50% or more decline in eGFR, end-stage kidney disease (ESKD), and mortality from a renal or cardiovascular cause by a significant 39% compared with placebo. Only 19 patients would need to be treated with the drug to prevent 1 event. The SGLT2 inhibitor reduced the risk for a similar secondary composite outcome excluding cardiovascular mortality by a significant 44%.
In addition, dapagliflozin significantly reduced the risk for dialysis, kidney transplantation, or renal death by 34%, Dr Heerspink reported.
Overall, results were consistent for patients with and without type 2 diabetes, UACR more or less than 1000 mg/g, eGFR higher or lower than 45 mL/min/1.73 m2, and systolic blood pressure higher or lower than 130 mm Hg.
Further, dapagliflozin reduced the risk for cardiovascular death or heart failure hospitalization by a significant 29% and all-cause mortality by a significant 31% compared with placebo.
“The impressive DAPA-CKD trial results are a remarkable development for patients with chronic kidney disease,” Dr Heerspink stated in a press release. “These data have the potential to transform the standard of care for this patient population, which has a significant unmet need for new and improved treatment options.”
Dapagliflozin was well-tolerated. Similar proportions of the SGLT2 inhibitor and placebo groups discontinued treatment (12.8% vs 14.4%; for adverse events [AEs]: 5.5% vs 5.7%, respectively). Serious AEs occurred in 29.5% vs 33.9%, respectively. No dapagliflozin recipients experienced diabetic ketoacidosis. Other AEs of interest included amputation (1.6% vs 1.8%), fracture (4.0% vs 3.2%), renal-related event (7.2% vs 8.7%), major hypoglycemia (0.7% vs 1.3%), and volume depletion (5.9% vs 4.2%), respectively.
This clinical trial was supported by AstraZeneca, the makers of dapagliflozin (Farxiga®). Please see the original reference for a full list of authors’ disclosures.
Heerspink H, Stefansson BV, Chertow GM, et al. DAPA-CKD — Dapagliflozin in patients with chronic kidney disease. Presented at ESC Virtual Congress 2020, August 30, 2020.
Farxiga demonstrated unprecedented reduction in the risk of kidney failure and cardiovascular or renal death in patients with chronic kidney disease in the phase III DAPA-CKD trial [press release]. AstraZeneca; August 30, 2020.