FREEDOM COVID Anticoagulation Strategy Randomized Trial - FREEDOM COVID

May 02, 2023
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Kim A. Eagle, MD, MACC
Date Presented:
03/06/2023
Date Published:
05/01/2023
Date Updated:
05/02/2023
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:

Highlighted text has been updated as of May 2, 2023.

Stone GW, Farkouh ME, Lala A, et al., on behalf of the FREEDOM COVID Anticoagulation Strategy Randomized Trial Investigators. Randomized Trial of Anticoagulation Strategies for Noncritically Ill Patients Hospitalized With COVID-19. J Am Coll Cardiol 2023;81:1747-62.

Editorial Comment: Vaduganathan M, Bikdeli B. Closer to FREEDOM From Uncertainty. J Am Coll Cardiol 2023;81:1763-5.

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


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