Dapagliflozin and Kidney Outcomes in Hospitalized Patients with COVID-19 Infection: An Analysis of the DARE-19 Randomized Controlled Trial.

Autor:	Heerspink HJL; University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.; The George Institute for Global Health, Newtown, NSW, Australia., Furtado RHM; Academic Research Organization, Hospital Israelita Albert Einstein, São Paulo, Brazil.; Instituto do Coracao do Hospital das Clinicas da FMUSP, São Paulo, Brazil., Berwanger O; Academic Research Organization, Hospital Israelita Albert Einstein, São Paulo, Brazil., Koch GG; Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina., Martinez F; National University of Córdoba, Córdoba, Argentina., Mukhtar O; Department of Medicine, Experimental Medicine and Immunotherapeutics Division, University of Cambridge, Cambridge, United Kingdom., Verma S; Division of Cardiac Surgery, Keenan Research Centre for Biomedical Science, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada.; Department of Surgery and Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada., Gasparyan SB; Late-stage Development, CVRM, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Tang F; Saint Luke's Mid America Heart Institute, Kansas City, Missouri., Windsor SL; Saint Luke's Mid America Heart Institute, Kansas City, Missouri., de Souza-Dantas VC; Intensive Care Unit, University Hospital Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Del Sueldo M; Department of Cardiology, Clinica de Especialidades, Villa Maria, Argentina., Frankel R; Cardiology, Maimonides Medical Center, New York, New York., Javaheri A; Washington University School of Medicine, St Louis, Missouri., Maldonado RA; Nephrology and Transplantation Service, Clínica Privada Vélez Sarsfield, Postgraduate School of Nephrology, National University of Córdoba, Córdoba, Argentina., Morse C; Wake Forest School of Medicine, Winston-Salem, North Carolina., Mota-Gomes M; Centro Universitário Cesmac/Hospital do Coração de Alagoas, Maceió, Brazil., Shemin D; Division of Kidney Diseases and Hypertension, Alpert Medical School of Brown University, Providence, Rhode Island., Silva OL Jr; Centro Integrado de Pesquisas, Hospital de Base-São José do Rio Preto, São José do Rio Preto, Brazil., Tognon AP; Academic Research Organization, Hospital Israelita Albert Einstein, São Paulo, Brazil., Twahirwa M; Diabetes and Endocrinology Institute, Doctors Hospital at Renaissance, Edinburg, Texas., Buenconsejo J; Late-stage Development, CVRM, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland., Esterline R; Late-stage Development, CVRM, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland., Oscarsson J; Late-stage Development, CVRM, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Ambery P; Late-stage Development, CVRM, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Langkilde AM; Late-stage Development, CVRM, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Kosiborod MN; The George Institute for Global Health, Newtown, NSW, Australia.; Saint Luke's Mid America Heart Institute, Kansas City, Missouri.; School of Medicine, University of Missouri-Kansas City, Kansas City, Missouri.
Jazyk:	angličtina
Zdroj:	Clinical journal of the American Society of Nephrology : CJASN [Clin J Am Soc Nephrol] 2022 May; Vol. 17 (5), pp. 643-654. Date of Electronic Publication: 2022 Apr 28.
DOI:	10.2215/CJN.14231021
Abstrakt:	Background and Objectives: Patients who were hospitalized with coronavirus disease 2019 (COVID-19) infection are at high risk of AKI and KRT, especially in the presence of CKD. The Dapagliflozin in Respiratory Failure in Patients with COVID-19 (DARE-19) trial showed that in patients hospitalized with COVID-19, treatment with dapagliflozin versus placebo resulted in numerically fewer participants who experienced organ failure or death, although these differences were not statistically significant. We performed a secondary analysis of the DARE-19 trial to determine the efficacy and safety of dapagliflozin on kidney outcomes in the overall population and in prespecified subgroups of participants defined by baseline eGFR. Design, Setting, Participants, & Measurements: The DARE-19 trial randomized 1250 patients who were hospitalized (231 [18%] had eGFR <60 ml/min per 1.73 m 2 ) with COVID-19 and cardiometabolic risk factors to dapagliflozin or placebo. Dual primary outcomes (time to new or worsened organ dysfunction or death, and a hierarchical composite end point of recovery [change in clinical status by day 30]), and the key secondary kidney outcome (composite of AKI, KRT, or death), and safety were assessed in participants with baseline eGFR <60 and ≥60 ml/min per 1.73 m 2 . Results: The effect of dapagliflozin versus placebo on the primary prevention outcome (hazard ratio, 0.80; 95% confidence interval, 0.58 to 1.10), primary recovery outcome (win ratio, 1.09; 95% confidence interval, 0.97 to 1.22), and the composite kidney outcome (hazard ratio, 0.74; 95% confidence interval, 0.50 to 1.07) were consistent across eGFR subgroups ( P for interaction: 0.98, 0.67, and 0.44, respectively). The effects of dapagliflozin on AKI were also similar in participants with eGFR <60 ml/min per 1.73 m 2 (hazard ratio, 0.71; 95% confidence interval, 0.29 to 1.77) and ≥60 ml/min per 1.73 m 2 (hazard ratio, 0.69; 95% confidence interval, 0.37 to 1.29). Dapagliflozin was well tolerated in participants with eGFR <60 and ≥60 ml/min per 1.73 m 2 . Conclusions: The effects of dapagliflozin on primary and secondary outcomes in hospitalized participants with COVID-19 were consistent in those with eGFR below/above 60 ml/min per 1.73 m 2 . Dapagliflozin was well tolerated and did not increase the risk of AKI in participants with eGFR below or above 60 ml/min per 1.73 m 2 . (Copyright © 2022 by the American Society of Nephrology.)
Databáze:	MEDLINE
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