The FREEDOM COVID Anticoagulation trial failed to demonstrate that therapeutic anticoagulation compared with prophylactic anticoagulation reduces 30-day composite events among non-critically ill patients hospitalized with COVID-19. However, fewer patients who received therapeutic anticoagulation died or required intubation.
COVID-19 can cause micro- and macrovascular complications, but whether therapeutic-dose anticoagulation improves the prognosis of non-critically ill patients with COVID-19 is uncertain. Thus, the FREEDOM COVID Anticoagulation trial (NCT04512079) was set up to compare prophylactic-dose with therapeutic-dose anticoagulation in patients hospitalized with COVID-19 not requiring intensive care unit (ICU) treatment.1 Valentín Fuster, MD, PhD, presented the results at the American College of Cardiology 2023 Annual Scientific Sessions.
The modified intention-to treat-population included 3,398 participants (average age, 53; 40% women) from 76 centers in 10 countries who were randomized to open-label prophylactic-dose enoxaparin (N=1,141), therapeutic-dose enoxaparin (N=1,136), or therapeutic-dose apixaban (N=1,121). The primary effectiveness endpoint was time to first event rate within 30 days of all-cause mortality, intubation requiring mechanical ventilation, systemic thromboembolism, or ischemic stroke. This composite endpoint was assessed in the prophylactic-dose group and compared with the two therapeutic-dose groups taken together. The primary safety endpoint was the in-hospital rate of major bleeding.
At 30 days, the primary effectiveness outcome was not statistically significant and 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). Yet, the difference in all-cause mortality was “very significant,” according to Dr. Fuster, occurring in 7.0% of patients treated with prophylactic-dose enoxaparin versus 4.9% of patients treated with therapeutic-dose anticoagulation (HR, 0.70; 95% CI, 0.52–0.93; P=0.01). Mortality was similar for therapeutic-dose enoxaparin (4.9%) and apixaban (5.0%). Intubation was required in 8.4% of the prophylactic-dose group versus 6.4% of patients in the combined therapeutic-dose groups (HR, 0.75; 95% CI, 0.58–0.98; P=0.03). The safety endpoint of major bleeding was infrequent in all three groups.
Dr. Fuster said the number of primary events was lower than expected—mainly due to a low event rate in India—which reduces the study’s power. “Based on these findings,” he concluded, “the use of therapeutic-dose anticoagulation may improve outcomes in non-critically ill patients hospitalized with COVID-19 who are at increased risk for adverse events but do not yet require ICU-level of care.”
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