Thromb Haemost 2020; 120(12): 1691-1699
DOI: 10.1055/s-0040-1720978
Blood Cells, Inflammation and Infection

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

Henny H. Billett*
1  Division of Hematology, Departments of Oncology and Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, United States
,
Morayma Reyes-Gil*
2  Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, United States
,
2  Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, United States
,
Kenji Ikemura
2  Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, United States
,
Lindsay R. Stahl
3  Montefiore Information Technology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, United States
,
Yungtai Lo
4  Department of Epidemiology and Population Health and Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, United States
,
Shafia Rahman
1  Division of Hematology, Departments of Oncology and Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, United States
,
Jesus D. Gonzalez-Lugo
1  Division of Hematology, Departments of Oncology and Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, United States
,
Margarita Kushnir
1  Division of Hematology, Departments of Oncology and Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, United States
,
Mohammad Barouqa
2  Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, United States
,
Ladan Golestaneh
5  Division of Nephrology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, United States
,
Eran Bellin*
4  Department of Epidemiology and Population Health and Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, United States
› Author Affiliations

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.

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.


Supplementary Material



Publication History

Received: 25 August 2020

Accepted: 24 September 2020

Publication Date:
13 November 2020 (online)

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