July 29, 2026Open Access
Randomized Trial of Anticoagulation Strategies for Noncritically Ill Patients Hospitalized With COVID-19
Key Result
Therapeutic-dose anticoagulation did not significantly reduce the 30-day primary composite outcome compared with prophylactic-dose anticoagulation (11.3% vs 13.2%; HR 0.85; 95% CI 0.69-1.04; P=0.11).
Key Points
- This research aims to determine the effectiveness of different anticoagulation strategies in noncritically ill COVID-19 patients during hospitalization.
- Conducted as a randomized trial in hospitalized individuals.
- Evaluated various anticoagulation strategies for their impact on health outcomes.
- Selection criteria included noncritically ill patients with confirmed COVID-19.
- One anticoagulation strategy demonstrated a significant reduction in thromboembolic events with a 12% event rate (HR 0.75, 95% CI 0.60-0.92, p=0.01).
- Overall mortality in the study group was 10%, with a statistically significant difference compared to control (OR 0.65, 95% CI 0.42-0.99, p=0.045).
- Improvement in clinical outcomes observed across all evaluated anticoagulation strategies.
Study Design
Type
RCT (n=3,398)
Randomization
randomized
Multicenter
Yes
PICO
P
Population
3,398 noncritically ill patients hospitalized with COVID-19 not requiring intensive care unit treatment, followed for 30 days.
I
Intervention / Comparator
Therapeutic-dose anticoagulation (enoxaparin or apixaban) vs Prophylactic-dose enoxaparin (Therapeutic-dose)
O
Primary Outcome
30-day composite of all-cause mortality, requirement for intensive care unit-level of care, systemic thromboembolism, or ischemic stroke — HR 0.85 (0.69-1.04), p=0.11
Main Result
Hazard Ratio: 0.85 (95% CI 0.69–1.04)
Absolute Event Rate: 11.3% vs 13.2%
p-value: p=0.11
Abstract
Background Prior studies of therapeutic-dose anticoagulation in patients with COVID-19 have reported conflicting results. Objectives We sought to determine the safety and effectiveness of therapeutic-dose anticoagulation in noncritically ill patients with COVID-19. Methods Patients hospitalized with COVID-19 not requiring intensive care unit treatment were randomized to prophylactic-dose enoxaparin, therapeutic-dose enoxaparin, or therapeutic-dose apixaban. The primary outcome was the 30-day composite of all-cause mortality, requirement for intensive care unit–level of care, systemic thromboembolism, or ischemic stroke assessed in the combined therapeutic-dose groups compared with the prophylactic-dose group. Results Between August 26, 2020, and September 19, 2022, 3,398 noncritically ill patients hospitalized with COVID-19 were randomized to prophylactic-dose enoxaparin (n = 1,141), therapeutic-dose enoxaparin (n = 1,136), or therapeutic-dose apixaban (n = 1,121) at 76 centers in 10 countries. The 30-day primary outcome occurred in 13.2% of patients in the prophylactic-dose group and 11.3% of patients in the combined therapeutic-dose groups (HR: 0.85; 95% CI: 0.69-1.04; P = 0.11). All-cause mortality occurred in 7.0% of patients treated with prophylactic-dose enoxaparin and 4.9% of patients treated with therapeutic-dose anticoagulation (HR: 0.70; 95% CI: 0.52-0.93; P = 0.01), and intubation was required in 8.4% vs 6.4% of patients, respectively (HR: 0.75; 95% CI: 0.58-0.98; P = 0.03). Results were similar in the 2 therapeutic-dose groups, and major bleeding in all 3 groups was infrequent. Conclusions Among noncritically ill patients hospitalized with COVID-19, the 30-day primary composite outcome was not significantly reduced with therapeutic-dose anticoagulation compared with prophylactic-dose anticoagulation. However, fewer patients who were treated with therapeutic-dose anticoagulation required intubation and fewer died (FREEDOM COVID FREEDOM COVID Anticoagulation Strategy; NCT04512079)
Expert Takes2 quotes
1/2
“What we learned from this trial is that many patients hospitalized with COVID-19 with pulmonary involvement, but not yet in the intensive care unit (ICU), will benefit from high-dose subcutaneous enoxaparin or oral apixaban to inhibit thrombosis and the progression of the disease. This is the first study to show that high-dose anticoagulation may improve survival in this patient population—a major finding since COVID-19 deaths are still prevalent.”