FREEDOM COVID Anticoagulation Strategy Randomized Trial - FREEDOM COVID

Mar 06, 2023
Font Size
A
A
A
Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Kim A. Eagle, MD, MACC
Date Presented:
03/06/2023
Date Published:
03/06/2023
Original Posted Date:
03/06/2023
References

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