The VA is the largest integrated health care system in the United States, providing an unprecedented opportunity to examine the impact of COVID-19 on health outcomes. Prior studies link SARS-CoV-2 infection to a hypercoagulable state and an increased risk of venous thromboembolism (VTE), arterial thrombosis, and death. Whether prophylactic anticoagulation reduces the risk of mortality or initiation of therapeutic anticoagulation is unclear.
To determine if prophylactic anticoagulation prescribed within 24 hours of hospital admission reduces the risk of 30 day mortality (Aim 1), inpatient mortality (Aim 2), and initiation of therapeutic anticoagulation among patients with SARS-CoV-2 infection.
We conducted a retrospective cohort study of all SARS-CoV-2 infected patients hospitalized in the VA on or after March 1, 2020. Aims were limited to patients with laboratory-confirmed SARS-CoV-2 positive test on or within 14 days prior to admission and without pre-existing anticoagulation. Exposure was initiation of prophylactic anticoagulation within 24 hours of admission. Outcome variables were 30-day mortality, inpatient mortality, and initiation of therapeutic anticoagulation as a surrogate for VTE or arterial thrombosis. We extracted demographics, baseline comorbidities, substance use, medication history, vital signs on admission, and laboratory data on admission. These variables were defined with a combination of ICD-10/CPT codes, laboratory values and medication data from CDW. We constructed inverse probability of treatment (IPT)-weighted Cox proportional hazards regression models to assess associations between exposure and outcomes. We constructed IPT-weighted Kaplan Meier plots to assist with interpretation of results. Sensitivity analyses will consider altering exposure windows (e.g., extending exposure window to 48 hours), performing quantitative bias analyses, capping propensity scores, and power permitting, stratified analyses by race/ethnicity, gender, and geographic location.
Of 4297 patients admitted to hospital with COVID-19, 3627 (84.4%) received prophylactic anticoagulation within 24 hours of admission. More than 99% (n=3600) of treated patients received subcutaneous heparin or enoxaparin. 622 deaths occurred within 30 days of hospital admission, 513 among those who received prophylactic anticoagulation. Most deaths (510/622, 82%) occurred during hospital stay. Using inverse probability of treatment weighted analyses, the cumulative incidence of mortality at 30 days was 14.3% (95% confidence interval 13.1% to 15.5%) among those who received prophylactic anticoagulation and 18.7% (15.1% to 22.9%) among those who did not. Compared with patients who did not receive prophylactic anticoagulation, those who did had a 27% decreased risk for 30 day mortality (hazard ratio 0.73, 95% confidence interval 0.66 to 0.81). Similar associations were found for inpatient mortality and initiation of therapeutic anticoagulation. Receipt of prophylactic anticoagulation was not associated with increased risk of bleeding that required transfusion (hazard ratio 0.87, 0.71 to 1.05). Quantitative bias analysis showed that results were robust to unmeasured confounding (e-value lower 95% confidence interval 1.77 for 30 day mortality). Results persisted in several sensitivity analyses.
This work provides critical evidence, lacking to date, to support prophylactic anticoagulation among patients admitted to VA facilities with SARS-CoV-2 infection. We expect these data to be generalizable to non-Veteran populations. Our findings were published in the British Medical Journal.
None at this time.
Cardiovascular Disease, Infectious Diseases
TRL - Applied/Translational
Best Practices, Cardiovascular Disease, Pharmacology
None at this time.