Dapagliflozin And Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD)

Background Patients with chronic kidney disease (CKD) are at high risk of adverse renal and cardiovascular (CV) outcomes, particularly heart failure. We investigated the effects of dapagliflozin inpatients with CKD, with and without type 2 diabetes (T2D). DAPA-CKD is the first trial to test the effects of a SGLT2 inhibitor on renal and CV outcomes in CKD patients without T2D and included patients with a lower eGFR than in prior trials. Methods We enrolled CKD patients with and withoutT2D with estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73m2 and UACR200-5000 mg/g, randomized (1:1) to dapagliflozin (10 mg once daily) or placebo. Patients were maintained on a stable dose of ACE inhibitor or ARB for ≥4 weeks before screening, if not contraindicated. The primary composite endpoint was worsening of kidney function (≥50% decline in eGFR, occurrence of end-stage kidney disease [ESKD]), or renal or CV death. Secondary endpoints were (in hierarchical order): (1) renal composite (primary endpoint without CV death); (2) composite of CV death or hospitalization for heart failure (hHF); and (3) death from any cause. The trial was stopped early following routine review by the data monitoring committee, because of overwhelming evidence of efficacy. Results Overall, 4304 patients were randomized at386 centers in 21 countries; 2152 to dapagliflozin, 2152 to placebo. The mean age was 62 years and 67% were male. Mean eGFR was 43.1 mL/min/1.73m2 and mean UACR was 949 mg/g. At baseline, 2906 (67.5%) patients had T2D, 96% had a history of hypertension, 37% other CV disease, and 11% heart failure. 4174(97%) were receiving an ACEi/ARB or another renin-angiotensin system blocker. Baseline characteristics were balanced between treatment groups. The sponsor has announced that in DAPA-CKD the primary and each of the secondary endpoints was reduced significantly by dapagliflozin compared with placebo. Conclusions Dapagliflozin significantly reduced the risk of CKD progression, the incidence of CV death/hHF, and prolonged survival in patients with CKD, with and without T2D. This presentation will report the prespecified primary and secondary outcomes in detail, along with additional information on heart failure outcomes. (Funded by AstraZeneca; NCT03036150)