Anticoagulation in COVID-19: Effect of Enoxaparin, Heparin and Apixaban on Mortality

Abstract

Background: Mortality in coronavirus disease of 2019 (COVID-19) is associated with increases in prothrombotic parameters, particularly D-dimer levels. Many institutions have adopted anticoagulation guidelines, often adjusted for illness severity. We wanted to investigate whether anticoagulation improves survival in COVID-19 and if this improvement in survival is associated with disease severity.Methods: To simulate an intention to treat clinical trial, we analyzed the effect on mortality of anticoagulation therapy chosen in the first 48 hours of hospitalization. We analyzed 3,625 COVID-19+ inpatients, controlling for age, GFR, oxygen saturation, ventilation requirement and time period, all determined during the first 48 hours.Findings: Adjusted logistic regression analyses demonstrated a significant decrease in mortality with prophylactic use of apixaban (OR 0·52, p=0·005) and enoxaparin (OR=0·50, p=0·002). Therapeutic apixaban was also associated with decreased mortality (OR 0·63, p=0·025) but was not more beneficial than prophylactic use. UFH did not show the same benefit. Higher D-dimer levels were associated with increased mortality (p10ug/ml derived the most benefit. There was no increase in transfusion requirement with any of the anticoagulants used.Interpretation: We conclude that COVID-19+ patients with moderate or severe illness benefit from anticoagulation and that apixaban has similar efficacy to enoxaparin in decreasing mortality in this disease.Funding: There was no internal or external funding support for this study.Declaration of Interests: HHB has received research or advisory funding from Bristol Myers Squibb, Janssen Pharmaceuticals, Bayer, and Kedrion Pharmaceuticals. MK has received research or advisory funding from Bristol Myers Squibb and Janssen Pharmaceuticals. All other authors declare no competing interests. Ethics Approval Statement: Institutional Review Board approval was obtained from Albert Einstein College of Medicine.