Hiddo J L Heerspink1,2, C David Sjöström3, Niels Jongs1, Glenn M Chertow4, Mikhail Kosiborod2,5,6, Fan Fan Hou7, John J V McMurray8, Peter Rossing9,10, Ricardo Correa-Rotter11, Raisa Kurlyandskaya12, Bergur V Stefansson3, Robert D Toto13, Anna Maria Langkilde3, David C Wheeler2,14. 1. Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, PO Box 30 001, 9700 RB Groningen, Netherlands. 2. The George Institute for Global Health, Level 5, 1 King Street, Newtown, Sydney, NSW 2042, Australia. 3. Late-stage Development, Cardiovascular, Renal and Metabolism, Biopharmaceuticals R&D, AstraZeneca, Pepparedsleden 1, 431 50 Mölndal, Gothenburg, Sweden. 4. Department of Medicine, 291 Campus Drive, Li Ka Shing Building, Stanford University School of Medicine, Stanford, CA 94305-5101 USA; Department of Epidemiology and Population Health, 150 Governor's LaneHRP Redwood Building Stanford University School of Medicine, Stanford, CA 94305-5405 USA. 5. Saint Luke's Mid America Heart Institute, 4401 Wornall Rd. Kansas City, MO 64111, USA. 6. University of Missouri-Kansas City, 5000 Holmes St, Kansas City, MO 64110, USA. 7. Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, 1838 Guangzhou N Ave, Baiyun, Guangzhou, Guangdong Province, China. 8. Institute of Cardiovascular and Medical Sciences, University of Glasgow, 126 University Pl, Glasgow, G12 8TA, UK. 9. Steno Diabetes Center Copenhagen, Niels Steensens Vej 2, 2820 Gentofte, Denmark. 10. Department of Clinical Medicine, University of Copenhagen, Blegdamsvej 3B, 33.5.18-21DK-2200 Copenhagen, Denmark. 11. National Medical Science and Nutrition Institute Salvador Zubirán, Vasco de Quiroga 15, Belisario Dom쭧uez Secc 16, Tlalpan, 14080 Ciudad de México, CDMX, Mexico. 12. Late-Stage Development, Cardiovascular, Renal and Metabolism, Biopharmaceuticals R&D, AstraZeneca, Postępu 14, 02-676 Warsaw, Poland. 13. Department of Internal Medicine, UT Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA. 14. Department of Renal Medicine, UCL Medical School, University College London, Rowland Hill Street, London, NW3 2PF, UK.
Abstract
AIMS: Mortality rates from chronic kidney disease (CKD) have increased in the last decade. In this pre-specified analysis of the DAPA-CKD trial, we determined the effects of dapagliflozin on cardiovascular and non-cardiovascular causes of death. METHODS AND RESULTS: DAPA-CKD was an international, randomized, placebo-controlled trial with a median of 2.4 years of follow-up. Eligible participants were adult patients with CKD, defined as a urinary albumin-to-creatinine ratio (UACR) 200-5000 mg/g and an estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73 m2. All-cause mortality was a key secondary endpoint. Cardiovascular and non-cardiovascular death was adjudicated by an independent clinical events committee. The DAPA-CKD trial randomized participants to dapagliflozin 10 mg/day (n = 2152) or placebo (n = 2152). The mean age was 62 years, 33% were women, the mean eGFR was 43.1 mL/min/1.73 m2, and the median UACR was 949 mg/g. During follow-up, 247 (5.7%) patients died, of whom 91 (36.8%) died due to cardiovascular causes, 102 (41.3%) due to non-cardiovascular causes, and in 54 (21.9%) patients, the cause of death was undetermined. The relative risk reduction for all-cause mortality with dapagliflozin (31%, hazard ratio [HR] [95% confidence interval (CI)] 0.69 [0.53, 0.88]; P = 0.003) was consistent across pre-specified subgroups. The effect on all-cause mortality was driven largely by a 46% relative risk reduction of non-cardiovascular death (HR [95% CI] 0.54 [0.36, 0.82]). Deaths due to infections and malignancies were the most frequently occurring causes of non-cardiovascular deaths and were reduced with dapagliflozin vs. placebo. CONCLUSION: In patients with CKD, dapagliflozin prolonged survival irrespective of baseline patient characteristics. The benefits were driven largely by reductions in non-cardiovascular death.
RCT Entities:
AIMS: Mortality rates from chronic kidney disease (CKD) have increased in the last decade. In this pre-specified analysis of the DAPA-CKD trial, we determined the effects of dapagliflozin on cardiovascular and non-cardiovascular causes of death. METHODS AND RESULTS:DAPA-CKD was an international, randomized, placebo-controlled trial with a median of 2.4 years of follow-up. Eligible participants were adult patients with CKD, defined as a urinary albumin-to-creatinine ratio (UACR) 200-5000 mg/g and an estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73 m2. All-cause mortality was a key secondary endpoint. Cardiovascular and non-cardiovascular death was adjudicated by an independent clinical events committee. The DAPA-CKD trial randomized participants to dapagliflozin 10 mg/day (n = 2152) or placebo (n = 2152). The mean age was 62 years, 33% were women, the mean eGFR was 43.1 mL/min/1.73 m2, and the median UACR was 949 mg/g. During follow-up, 247 (5.7%) patientsdied, of whom 91 (36.8%) died due to cardiovascular causes, 102 (41.3%) due to non-cardiovascular causes, and in 54 (21.9%) patients, the cause of death was undetermined. The relative risk reduction for all-cause mortality with dapagliflozin (31%, hazard ratio [HR] [95% confidence interval (CI)] 0.69 [0.53, 0.88]; P = 0.003) was consistent across pre-specified subgroups. The effect on all-cause mortality was driven largely by a 46% relative risk reduction of non-cardiovascular death (HR [95% CI] 0.54 [0.36, 0.82]). Deaths due to infections and malignancies were the most frequently occurring causes of non-cardiovascular deaths and were reduced with dapagliflozin vs. placebo. CONCLUSION: In patients with CKD, dapagliflozin prolonged survival irrespective of baseline patient characteristics. The benefits were driven largely by reductions in non-cardiovascular death.
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