AntiCoagulaTIon cOroNavirus - ACTION

Contribution To Literature:

The ACTION trial failed to show that therapeutic anticoagulation during COVID-19 infection was beneficial.


The goal of the trial was to evaluate therapeutic anticoagulation compared with prophylactic anticoagulation among patients admitted with coronavirus disease 2019 (COVID-19) infection.

Study Design

  • Randomized
  • Parallel

Patients admitted with COVID-19 infection were randomized to therapeutic anticoagulation (n = 311) versus prophylactic anticoagulation (n = 304). Stable patients received rivaroxaban 20 mg daily. Unstable patients received enoxaparin 1 mg/kg twice daily.

  • Total number of enrollees: 615
  • Duration of follow-up: 30 days
  • Mean patient age: 57 years
  • Percentage female: 38%
  • Percentage with diabetes: 27%

Inclusion criteria:

  • Patients ≥18 years admitted with COVID-19 infection
  • Elevated D-dimer

Exclusion criteria:

  • Indication for therapeutic anticoagulation
  • Estimated creatinine clearance <30 ml/min
  • Platelet count <50,000/m3
  • Use of aspirin or P2Y12 inhibitor
  • High-risk of bleeding

Other salient features/characteristics:

  • Need for oxygen in 76% (catheter or mask 60%, high-flow nasal cannula 8%, tracheal intubation 7%)

Principal Findings:

The primary outcome, hierarchical analysis of mortality, duration of hospitalization, and duration of oxygen use through 30 days, occurred in 34.8% of the therapeutic anticoagulation group compared with 41.3% of the prophylactic anticoagulation group (p = nonsignificant).

Secondary outcomes:

  • All-cause mortality: 11.3% of the therapeutic anticoagulation group compared with 7.6% of the prophylactic anticoagulation group (p = nonsignificant)
  • Venous thromboembolism: 3.5% of the therapeutic anticoagulation group compared with 5.9% of the prophylactic anticoagulation group (p = nonsignificant)
  •  International Society on Thrombosis and Hemostasis (ISTH) major bleeding: 8.4% of the therapeutic anticoagulation group compared with 2.3% of the prophylactic anticoagulation group (p < 0.05)


Among patients admitted with COVID-19 infection with elevated D-dimer, therapeutic anticoagulation was not superior to prophylactic anticoagulation. Rivaroxaban for stable patients and enoxaparin for unstable patients did not improve clinical outcomes; however, major bleeding was increased.


Lopes RD, de Barros e Silva PG, Furtado RH, et al. Therapeutic versus prophylactic anticoagulation for patients admitted to hospital with COVID-19 and elevated D-dimer concentration (ACTION): an open-label, multicentre, randomised, controlled trial. Lancet 2021;397:2253-63.

Presented by Dr. Renato D. Lopes at the American College of Cardiology Virtual Annual Scientific Session (ACC 2021), May 16, 2021.

Clinical Topics: Anticoagulation Management, COVID-19 Hub, Prevention, Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine, Anticoagulation Management and Venothromboembolism

Keywords: ACC21, ACC Annual Scientific Session, Anticoagulants, Blood Coagulation, Coronavirus, Coronavirus Infections, COVID-19, Hemorrhage, Intubation, Intratracheal, Primary Prevention, Venous Thromboembolism

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