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. Anticoagulation has been proposed as therapy to decrease mortality, often adjusted for illness severity.

Objective We wanted to investigate whether anticoagulation improves survival in COVID-19 and if this improvement in survival is associated with disease severity.

Methods This is a cohort study simulating an intention-to-treat clinical trial, by analyzing 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, gender, glomerular filtration rate, oxygen saturation, ventilation requirement, intensive care unit admission, and time period, all determined during the first 48 hours.

Results Adjusted logistic regression analyses demonstrated a significant decrease in mortality with prophylactic use of apixaban (odds ratio [OR] 0.46, p = 0.001) and enoxaparin (OR = 0.49, p = 0.001). Therapeutic apixaban was also associated with decreased mortality (OR 0.57, p = 0.006) but was not more beneficial than prophylactic use when analyzed over the entire cohort or within D-dimer stratified categories. Higher D-dimer levels were associated with increased mortality (p < 0.0001). When adjusted for these same comorbidities within D-dimer strata, patients with D-dimer levels < 1 µg/mL did not appear to benefit from anticoagulation while patients with D-dimer levels > 10 µg/mL derived the most benefit. There was no increase in transfusion requirement with any of the anticoagulants used.

Conclusion 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.

Keywords

anticoagulation - apixaban - COVID-19 - D-dimer - enoxaparin - mortality

Note

For original data, please contact the corresponding author.

Authors' Contributions

H.H.B. originated the concept, helped in the analysis, and wrote the manuscript. M.R.G. helped originate the concept, helped in the analysis, and reviewed and edited the manuscript. J.S. helped in the statistical analysis and reviewed and edited the manuscript. K.I. helped in the analysis and reviewed and edited the manuscript. L.S. developed the cohorts, helped in the statistical analysis, and reviewed and edited the manuscript. Y.L. helped in the statistical analysis and reviewed and edited the manuscript. S.R. reviewed patient data and reviewed and edited the manuscript. J.D.G.L. reviewed patient data and reviewed and edited the manuscript. M.K. reviewed the data and edited the manuscript. M.B. reviewed patient data and reviewed and edited the manuscript. L.G. reviewed the data and edited the manuscript. E.B. developed the CLG program, developed the cohorts, performed the statistical analyses, and reviewed and edited the manuscript.

^* Equal authorship.

Publication History

Received: 25 August 2020

Accepted: 24 September 2020

Article published online:
13 November 2020

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