Abstract 14850: Effect of Therapeutic-Dose Heparin on Acute Kidney Injury in Non-Critically Ill Hospitalized Patients With Covid-19: The Activ4a and Attac Randomized Trial

Abstract

Background: Acute kidney injury (AKI) is common in patients with COVID-19 and mediated, in part, by thromboinflammation. In non-critically ill patients with COVID-19, therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support. We investigated whether therapeutic-dose heparin reduces the incidence of AKI or death in non-critically ill patients hospitalized for COVID-19. Methods: Non-critically ill patients hospitalized for COVID-19 were enrolled in an open-label, multiplatform randomized trial of therapeutic-dose heparin versus usual-care pharmacologic thromboprophylaxis. The primary endpoint of this analysis was in-hospital diagnosis of AKI or death. AKI was defined as Kidney Disease Improving Global Outcomes stage 2 or 3 AKI (≥2-fold increase in serum creatinine or initiation of renal replacement therapy). A Bayesian statistical model estimated the risk of AKI or death between those randomized to therapeutic-dose anticoagulation versus usual-care thromboprophylaxis, adjusted for age, sex, D-dimer, time epoch, country, site, and platform. Results: Among 1922 enrolled from ACTIV4a and ATTACC, 23 were excluded due to ESRD at enrollment. Baseline or follow-up creatinine was missing for 205 individuals. Among 1694 participants analyzed, median age was 60, 58% were men, and median baseline creatinine was 0.9 mg/dL. The primary endpoint occurred in 83 participants (4.9%); 4.4% assigned to therapeutic-dose heparin and 5.5% assigned to thromboprophylaxis (adjusted relative risk [aRR] 0.72, 95% CrI 0.47-1.10; posterior probability of superiority [defined as relative risk < 1.0] was 93.6%). Therapeutic-dose anticoagulation was associated with a 97.7% probability of superiority to reduce the composite of stage 3 AKI or death (3.1% vs. 4.6%; aRR 0.64, 95% CrI 0.40-0.99) compared to usual-care thromboprophylaxis. Conclusions: Therapeutic-dose anticoagulation with heparin was associated with a high probability of superiority to reduce the incidence of in-hospital stage 3 AKI or death in non-critically ill patients hospitalized for COVID-19, compared with usual-care thromboprophylaxis.