TY - JOUR
T1 - Randomized Trial of Anticoagulation Strategies for Noncritically Ill Patients Hospitalized With COVID-19
AU - FREEDOM COVID Anticoagulation Strategy Randomized Trial Investigators
AU - Stone, Gregg W
AU - Farkouh, Michael E
AU - Lala, Anuradha
AU - Tinuoye, Elizabeth
AU - Dressler, Ovidiu
AU - Moreno, Pedro R
AU - Palacios, Igor F
AU - Goodman, Shaun G
AU - Esper, Rodrigo B
AU - Abizaid, Alexandre
AU - Varade, Deepak
AU - Betancur, Juan F
AU - Ricalde, Alejandro
AU - Payro, Gerardo
AU - Castellano, José María
AU - Hung, Ivan F N
AU - Nadkarni, Girish N
AU - Giustino, Gennaro
AU - Godoy, Lucas C
AU - Feinman, Jason
AU - Camaj, Anton
AU - Bienstock, Solomon W
AU - Furtado, Remo H M
AU - Granada, Carlos
AU - Bustamante, Jessica
AU - Peyra, Carlos
AU - Contreras, Johanna
AU - Owen, Ruth
AU - Bhatt, Deepak L
AU - Pocock, Stuart J
AU - Fuster, Valentin
N1 - Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
PY - 2023/5/9
Y1 - 2023/5/9
N2 - 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).
AB - 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).
KW - Humans
KW - COVID-19
KW - Enoxaparin/therapeutic use
KW - Anticoagulants/adverse effects
KW - Blood Coagulation
KW - Thromboembolism/prevention & control
U2 - 10.1016/j.jacc.2023.02.041
DO - 10.1016/j.jacc.2023.02.041
M3 - Article
C2 - 36889611
SN - 0735-1097
VL - 81
SP - 1747
EP - 1762
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 18
ER -