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Early initiation of prophylactic anticoagulation for prevention of COVID-19 mortality: a nationwide cohort study of hospitalized patients in the United States. medRxiv : the preprint server for health sciences Rentsch, C. T., Beckman, J. A., Tomlinson, L., Gellad, W. F., Alcorn, C., Kidwai-Khan, F., Skanderson, M., Brittain, E., King, J. T., Ho, Y. L., Eden, S., Kundu, S., Lann, M. F., Greevy, R. A., Ho, P. M., Heidenreich, P. A., Jacobson, D. A., Douglas, I. J., Tate, J. P., Evans, S. J., Atkins, D., Justice, A. C., Freiberg, M. S. 2020

Abstract

Deaths among patients with coronavirus disease 2019 (COVID-19) are partially attributed to venous thromboembolism and arterial thromboses. Anticoagulants prevent thrombosis formation, possess anti-inflammatory and anti-viral properties, and may be particularly effective for treating patients with COVID-19.To evaluate whether initiation of prophylactic anticoagulation within 24 hours of admission is associated with decreased risk of death among patients hospitalized with COVID-19.Observational cohort study.Nationwide cohort of patients receiving care in the Department of Veterans Affairs, the largest integrated healthcare system in the United States.All patients hospitalized with laboratory-confirmed SARS-CoV-2 infection March 1 to July 31, 2020, without a history of therapeutic anticoagulation.Prophylactic doses of subcutaneous heparin, low-molecular-weight heparin, or direct oral anticoagulants.30-day mortality. Secondary outcomes: inpatient mortality and initiating therapeutic anticoagulation.Of 4,297 patients hospitalized with COVID-19, 3,627 (84.4%) received prophylactic anticoagulation within 24 hours of admission. More than 99% (n=3,600) received subcutaneous heparin or enoxaparin. We observed 622 deaths within 30 days of admission, 513 among those who received prophylactic anticoagulation. Most deaths (510/622, 82%) occurred during hospitalization. In inverse probability of treatment weighted analyses, cumulative adjusted incidence of mortality at 30 days was 14.3% (95% CI 13.1-15.5) among those receiving prophylactic anticoagulation and 18.7% (95% CI 15.1-22.9) among those who did not. Compared to patients who did not receive prophylactic anticoagulation, those who did had a 27% decreased risk for 30-day mortality (HR 0.73, 95% CI 0.66-0.81). Similar associations were found for inpatient mortality and initiating therapeutic anticoagulation. Quantitative bias analysis demonstrated that results were robust to unmeasured confounding (e-value lower 95% CI 1.77). Results persisted in a number of sensitivity analyses.Early initiation of prophylactic anticoagulation among patients hospitalized with COVID-19 was associated with a decreased risk of mortality. These findings provide strong real-world evidence to support guidelines recommending the use of prophylactic anticoagulation as initial therapy for COVID-19 patients upon hospital admission.

View details for DOI 10.1101/2020.12.09.20246579

View details for PubMedID 33330896

View details for PubMedCentralID PMC7743107