BACKGROUND AND PURPOSE:

• Lopes et al. (The Lancet, 2021) compared the efficacy and safety of therapeutic versus prophylactic anticoagulation in hospitalized COVID-19 patients

METHODS:

• Pragmatic, open-label, multicenter, randomized, controlled trial
• Setting
  • Brazil
• Participants
  • Hospitalized with COVID-19 and elevated D-dimer concentration
  • COVID-19 symptoms for up to 14 days before randomization
• Study design
  • Randomization to therapeutic vs prophylactic anticoagulation
• Therapeutic anticoagulation
  • Stable patients: Oral rivaroxaban (20 mg or 15 mg daily)
  • Clinically unstable patients: Subcutaneous enoxaparin (1 mg/kg twice per day) or IV unfractionated heparin (to achieve a 0.3–0.7 IU/mL anti-Xa concentration) followed by rivaroxaban to day 30
• Prophylactic anticoagulation
  • Standard in-hospital enoxaparin or unfractionated heparin at physicians discretion
• Statistical Analysis
  • Analyzed with the win ratio method (a ratio >1 reflects a better outcome in the therapeutic anticoagulation group) in the intention-to-treat population
  • Can be used to stratify and evaluate pairs in studies with multiple composite outcomes
• Primary efficacy outcome
  • Composite of: Time to death | Duration of hospitalization | Duration of supplemental oxygen to day 30
• Primary safety outcome
  • Major or clinically relevant non-major bleeding through 30 days

RESULTS:

• Therapeutic group: 311 patients | prophylactic group: 304 patients
  • Clinically stable: 94%
  • Clinically unstable: 6%
• The primary efficacy outcome was not different between patients assigned therapeutic or prophylactic anticoagulation
  • Therapeutic group: 38.4% wins
  • Prophylactic group: 41.3% wins
  • Win ratio 0.86 (95% CI, 0.59 to 1.22); P = 0.40
• Consistent results were seen in clinically stable and clinically unstable patients
• The primary safety outcome occurred in more patients in the therapeutic group
  • Therapeutic group: 8%
  • Prophylactic group: 2%
  • Relative risk 3.64 (95% CI, 1.61 to 8.27); P = 0.0010
• Allergic reactions
  • Therapeutic group: 1%
  • Prophylactic group: 1%

CONCLUSION:

• For hospitalized COVID-19 patients with elevated D-dimer levels, routine therapeutic anticoagulation did not provide a clinical benefit vs prophylactic anticoagulation and resulted in more bleeding episodes
• The authors conclude

Thus, the use of therapeutic-dose rivaroxaban, and other direct oral anticoagulants, should be avoided in hospitalised patients with COVID-19 who do not have an evidence-based indication for oral anticoagulation 

Learn More – Primary Sources:

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

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