Dapagliflozin and Kidney Outcomes in Hospitalized Patients with COVID-19 Infection
Creators: name: Javaheri, Ali
name: Furtado, Remo H M
name: Silva, Osvaldo Lourenço
name: de Souza-Dantas, Vicente Cés
name: Maldonado, Rafael A
name: Kosiborod, Mikhail N
name: Koch, Gary G
name: Tognon, Alexandre Pereira
name: Morse, Caryn
name: Twahirwa, Marcel
name: Mukhtar, Omar
name: Langkilde, Anna Maria
name: Gasparyan, Samvel B
name: Heerspink, Hiddo J L
name: Buenconsejo, Joan
name: Oscarsson, Jan
name: Verma, Subodh
name: Windsor, Sheryl L
name: Berwanger, Otavio
name: Esterline, Russell
name: Mota-Gomes, Marco
name: Martinez, Felipe
name: Shemin, Douglas
name: Frankel, Robert
name: Ambery, Philip
name: Tang, Fengming
name: Del Sueldo, Mildren
Publisher: name: Wolters Kluwer
Year: 2022

description: <p>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, &amp; MEASUREMENTS: The DARE-19 trial randomized 1250 patients who were hospitalized (231 [18%] had eGFR &lt;60 ml/min per 1.73 m<sup>2</sup>) 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 &lt;60 and &ge;60 ml/min per 1.73 m<sup>2</sup>. 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 (<em>P</em> for interaction: 0.98, 0.67, and 0.44, respectively). The effects of dapagliflozin on AKI were also similar in participants with eGFR &lt;60 ml/min per 1.73 m<sup>2</sup> (hazard ratio, 0.71; 95% confidence interval, 0.29 to 1.77) and &ge;60 ml/min per 1.73 m<sup>2</sup> (hazard ratio, 0.69; 95% confidence interval, 0.37 to 1.29). Dapagliflozin was well tolerated in participants with eGFR &lt;60 and &ge;60 ml/min per 1.73 m<sup>2</sup>. 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<sup>2</sup>. 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<sup>2</sup>.</p>