Early initiation of prophylactic anticoagulation for prevention of COVID-19 mortality: a nationwide cohort study of hospitalized patients in the United States

Link to article at PubMed

medRxiv. 2020 Dec 11:2020.12.09.20246579. doi: 10.1101/2020.12.09.20246579. Preprint.

ABSTRACT

IMPORTANCE: 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.

OBJECTIVE: 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.

DESIGN: Observational cohort study.

SETTING: Nationwide cohort of patients receiving care in the Department of Veterans Affairs, the largest integrated healthcare system in the United States.

PARTICIPANTS: All patients hospitalized with laboratory-confirmed SARS-CoV-2 infection March 1 to July 31, 2020, without a history of therapeutic anticoagulation.

EXPOSURES: Prophylactic doses of subcutaneous heparin, low-molecular-weight heparin, or direct oral anticoagulants.

MAIN OUTCOMES AND MEASURES: 30-day mortality. Secondary outcomes: inpatient mortality and initiating therapeutic anticoagulation.

RESULTS: 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.

CONCLUSIONS AND RELEVANCE: 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.

PMID:33330896 | PMC:PMC7743107 | DOI:10.1101/2020.12.09.20246579

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