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

Thromb Haemost. 2020 Dec;120(12):1691-1699. doi: 10.1055/s-0040-1720978. Epub 2020 Nov 13.

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.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anticoagulants / therapeutic use*
  • Biomarkers / metabolism
  • Blood Coagulation / drug effects*
  • COVID-19 / mortality
  • COVID-19 Drug Treatment*
  • Cohort Studies
  • Enoxaparin / therapeutic use*
  • Female
  • Fibrin Fibrinogen Degradation Products / metabolism
  • Heparin / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Pyrazoles / therapeutic use*
  • Pyridones / therapeutic use*
  • SARS-CoV-2 / physiology*
  • Survival Analysis

Substances

  • Anticoagulants
  • Biomarkers
  • Enoxaparin
  • Fibrin Fibrinogen Degradation Products
  • Pyrazoles
  • Pyridones
  • fibrin fragment D
  • apixaban
  • Heparin