Outpatient Venous Thromboembolism Prophylaxis for Patients with COVID-19

Following recognition of the association between COVID-19 and arterial and venous thromboembolism (VTE), numerous randomized, controlled trials were conducted to identify the ideal intensity of anticoagulant prophylaxis. Among hospitalized patients, findings suggested that therapeutic dose anticoagulation benefits those on hospital wards but not those in the intensive care unit (NEJM JW Gen Med Dec 15 2021 and BMJ 2021 Oct 14; 375:n2400). Whether outpatients with symptomatic COVID-19 should receive primary VTE prophylaxis is unknown.

In the open-label OVID trial, investigators in Switzerland and Germany randomized 472 symptomatic outpatients with COVID-19 to receive enoxaparin (40 mg daily for 14 days) or no thromboprophylaxis. Included patients were older than 50 years with respiratory symptoms or fever and a positive COVID-19 test within 5 days. The primary composite endpoint included hospitalization or death within 30 days; secondary composite outcomes included venous or arterial thrombosis.

Roughly half the patients were enrolled prior to COVID-19 vaccination. The study was discontinued early when a predefined independent data review indicated little chance that enoxaparin would be deemed superior to observation. The primary outcome was experienced by 3% of patients in each arm. Arterial or venous thrombosis was experienced by 1% of patients in the enoxaparin group and 2% in the control group (95% CI, 0.09–2.74). No safety concerns were noted.