Randomized Trial of Anticoagulation Strategies for Noncritically Ill Patients Hospitalized With COVID-19.
Link: https://doi.org/S0735-1097(23)04527-8
Authors: Stone, Gregg W; Farkouh, Michael E; Lala, Anuradha; Tinuoye, Elizabeth; Dressler, Ovidiu; Moreno, Pedro R; Palacios, Igor F; Goodman, Shaun G; Esper, Rodrigo B; Abizaid, Alexandre; Varade, Deepak; Betancur, Juan F; Ricalde, Alejandro; Payro, Gerardo; Castellano, José María; Hung, Ivan F N; Nadkarni, Girish N; Giustino, Gennaro; Godoy, Lucas C; Feinman, Jason; Camaj, Anton; Bienstock, Solomon W; Furtado, Remo H M; Granada, Carlos; Bustamante, Jessica; Peyra, Carlos; Contreras, Johanna; Owen, Ruth; Bhatt, Deepak L; Pocock, Stuart J; Fuster, Valentin; ,
Abstract: Prior studies of therapeutic-dose anticoagulation in patients with COVID-19 have reported conflicting results. We sought to determine the safety and effectiveness of therapeutic-dose anticoagulation in noncritically ill patients with COVID-19. 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. 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. 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).