Anticoagulation in non-critically ill hospitalised COVID patients

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 hospitalised with COVID-19. There was no difference between the 2 full-dose anticoagulation strategies, full-dose enoxaparin or apixaban in the primary and key secondary endpoints.

COVID-19 can cause microvascular 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 anticoagulation with therapeutic-dose anticoagulation in patients hospitalised with COVID-19 not requiring intensive care unit (ICU) treatment [1]. Prof. Valentín Fuster (Icahn School of Medicine at Mount Sinai, NY, USA) presented the results.

The modified intention-to-treat population consisted of 3,398 participants (average age 53 years; 40% women) from 76 centres in 10 countries. They were randomised to open-label prophylactic-dose enoxaparin (group A, n=1,141), therapeutic-dose enoxaparin (group B, n=1,136), or therapeutic-dose apixaban (group C, 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 ischaemic stroke. This composite endpoint was assessed in the prophylactic-dose group and compared with the 2 therapeutic-dose groups taken together. The primary safety endpoint was the in-hospital rate of major bleeding.

At 30 days, the difference in the primary effectiveness outcome was not statistically significant and occurred in 13.2% of patients in group A and 11.3% of patients in groups B and C combined (HR 0.85; 95% CI 0.69–1.04; P=0.11). All-cause mortality was nominally lower, occurring in 7.0% of patients in group A versus 4.9% of patients in groups B and C (HR 0.70; 95% CI 0.52–0.93; P=0.01; see Table). The safety endpoint of major bleeding was infrequent in all 3 groups: 1 (0.1%) in group A, 6 (0.5%) in group B, and 3 (0.3%) in group C.

Table: Results of the 30-day primary effectiveness components [1]

*This event was a haemorrhagic stroke and was not included as a component of the primary endpoint; there were no ischaemic strokes.

Prof. Fuster said that the number of primary events was lower than expected, mainly due to a low event rate in India, which reduced the study’s power. “Based on these findings,” he concluded, “the use of therapeutic-dose anticoagulation may improve outcomes in non-critically ill patients hospitalised with COVID-19 who are at increased risk for adverse events but do not yet require ICU level of care.” Results should be interpreted in the context of other trials evaluating intensity of anticoagulation in this population.

1. Fuster V, et al. Anticoagulation Strategies In Non-critically Ill Hospitalized Covid-19 Patients: Principal Outcomes Of The Freedom Covid Anticoagulation Trial. Session 410-12, ACC Scientific Session 2023, 4–6 March, New Orleans, USA.

 

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Posted on 7 June, 2023