FREEDOM COVID Anticoagulation Strategy Randomized Trial - FREEDOM COVID
Contribution To Literature:
The FREEDOM COVID trial failed to show that therapeutic vs. prophylactic anticoagulation reduced 30-day composite events; however, fewer patients were assigned to therapeutic anticoagulation diet or required intubation.
Description:
The goal of the trial was to evaluate prophylactic anticoagulation compared with therapeutic anticoagulation among non-critically ill patients hospitalized with coronavirus disease 2019 (COVID-19).
Study Design
- Block randomization
- Parallel
- Open-label
Non-critically ill patients hospitalized with COVID-19 were randomized to prophylactic enoxaparin (n = 1,141) vs. therapeutic enoxaparin (n = 1,136) vs. therapeutic apixaban (n = 1,121).
Prophylactic enoxaparin was given at a dose of 40 mg subcutaneous daily.
Therapeutic enoxaparin was given at a dose of 1 mg/kg subcutaneous twice daily.
Therapeutic apixaban was given at a dose of 5 mg orally twice daily.
- Total number of enrollees: 3,398
- Duration of follow-up: 30 days
- Mean patient age: 53 years
- Percentage female: 40%
- Percentage with diabetes: 22%
Inclusion criteria:
- Non-critically ill patients hospitalized with COVID-19
- Temperature >38º Celsius
- Oxygen saturation ≤94% (on room air)
- At least one of the following laboratory tests: D-dimer ≥1.0 μg/mL, C-reactive protein >2 mg/L, ferritin >300 μg/L, or lymphopenia <1500 cells/m3
Exclusion criteria:
- Intensive care unit (ICU)-level care
- Anticipated hospitalization <72 hours
- Treatment with anticoagulation within last 7 days
- Active bleeding or contraindication to anticoagulation
- End-stage renal disease
Principal Findings:
The primary outcome, all-cause mortality, ICU care, systemic thromboembolism, or ischemic stroke, occurred in 13.2% of the prophylactic enoxaparin group vs. 11.3% of the combined therapeutic groups (p = 0.11).
Secondary outcomes:
- All-cause mortality: 7.0% of the prophylactic enoxaparin group vs. 4.9% of the combined therapeutic groups (p = 0.01)
- Intubation: 8.4% of the prophylactic enoxaparin group vs. 6.4% of the combined therapeutic groups (p = 0.03)
- Major bleeding (Bleeding Academic Research Consortium [BARC] types 3 or 5): 0.1% of the prophylactic enoxaparin group vs. 0.4% of the combined therapeutic groups (p = 0.18)
Interpretation:
Among non-critically ill patients hospitalized with COVID-19, therapeutic anticoagulation did not reduce a 30-day composite endpoint; however, it was associated with a reduction in secondary outcomes of all-cause mortality and intubation compared with prophylactic anticoagulation. Bleeding was low and similar between treatment groups.
References:
Stone GW, Farkouh ME, Lala A, et al., on behalf of the FREEDOM COVID Anticoagulation Strategy Randomized Trial Investigators. Anticoagulation Strategies in Non-Critically Ill Patients Hospitalized With COVID-19: A Randomized Clinical Trial. J Am Coll Cardiol 2023;Mar 6:[Epub ahead of print].
Presented by Dr. Valentin Fuster at the American College of Cardiology Annual Scientific Session (ACC.23/WCC), New Orleans, LA, March 6, 2023.
Clinical Topics: Anticoagulation Management, COVID-19 Hub, Dyslipidemia, Prevention, Vascular Medicine, Lipid Metabolism
Keywords: ACC23, ACC Annual Scientific Session, Anticoagulants, COVID-19, C-Reactive Protein, Enoxaparin, Ferritins, Hemorrhage, Intensive Care Units, Intubation, Intratracheal, Ischemic Stroke, Lymphopenia, Primary Prevention, Thromboembolism
< Back to Listings