G CHERTOW 1, P VART 2, N JONGS 2, R TOTO 3, J GORRIZ 4, F HOU 5, J MCMURRAY 6, R CORREA-ROTTER 7, P ROSSING P8, C SJÖSTRÖM 9, B STEFÁNSSON 9, A LANGKILDE 9, D WHEELER 10, H HEERSPINK 11
1Stanford University School of Medicine, Palo Alto, United States of America, 2University of Groningen, Groningen, The Netherlands, 3Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA., Dallas, United States of America, 4Department of Nephrology, University Clinic hospital, INCLIVA,University of Valencia, Valencia, Spain, Valencia, Spain, 5Department of Medicine, Division of Nephrology, Southern Medical University, national Clinical Research Center for Kidney Disease, Guangzhou, China, Guangzhou, China, 6Institute of cardiovascular and medical sciences, university of glasgow, Glasgow, UK, Glasgow, Scotland, UK, 7National Medical Science and Nutrition Institute Salvador Zubiran, Mexico City, Mexico, Mexico City, Mexico, 8Steno Diabetes Center, Copenhagen, Gentofte, Denmark, Copenhagen, Denmark, 9Late-Stage Development, Cardiovascular, Renal and Metabolism, Biopharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden, Gothenburg, Sweeden, 10Department of Renal Medicine, University College London, London, UK, London, England, UK, 11Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, Groningen, The Netherlands., Groningen, The Netherlands
Background: The DAPA-CKD trial demonstrated that Sodium-glucose-co-transporter-type-2-inhibitor (SGLT2i), dapagliflozin significantly reduced risk of kidney failure, and prolonged survival in participants with CKD with/without T2DM. The DAPA-CKD trial enrolled patients with eGFR 25-75 ml/min/1.73m2. Little is known about the efficacy and safety of SGLT2i in patients with eGFR <30 ml/min/1.73m2. We compared effects of dapagliflozin on major kidney and cardiovascular outcomes in patients with eGFR >< 30 ml/min/1.73m2.
Methods: Patients with CKD, eGFR of 25-75 ml/min/1.73m2 and UACR 200-5000 mg/g, were randomized to dapagliflozin (10 mg/OD) or placebo. The primary composite endpoint was: sustained decline in eGFR ≥50%, ESKD, kidney or cardiovascular death. Secondary outcomes were:kidney composite ( primary endpoint, without cardiovascular death), composite of cardiovascular death or hHF, and death from any cause. Subgroup analyses were performed according to baseline eGFR (<30 &≥30 ml/min/1.73m2).
Results:Of 4304 patients enrolled, 624 participants had eGFR <30 and 3680 had eGFR ≥30 ml/min/1.73m2 at baseline. Patients with eGFR <30 ml/min/1.73m2 randomized to dapagliflozin (n=293) experienced 27% (95% CI:–2,47) reduction in the primary composite endpoint, 29% (–2, 51), 17% (–53, 55), and 32% (–21, 61) reductions in kidney, cardiovascular and mortality endpoints, respectively, vs placebo (n=331). Interaction p-values between eGFR <30 vs ≥30 ml/min/1.73m2 for these endpoints were 0.22, 0.13, 0.63, and 0.95, respectively. In patients with eGFR <30 ml/min/1.73m2, eGFR slope declined by 2.15 and 3.38 mL/min/1.73m2 /year in dapagliflozin and placebo groups, respectively. Rates of serious adverse events (SAE) and AE of special interest were similar with dapagliflozin or placebo.
Conclusion: Patients with eGFR <30 ml/min/1.73m2, with and without T2DM, dapagliflozin can reduce major kidney and cardiovascular events and attenuate progressive eGFR loss.
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