BACKGROUND AND PURPOSE:

• Sholzberg et al. (BMJ, 2021) compared therapeutic heparin vs prophylactic heparin among moderately ill, hospitalized COVID-19 patients

METHODS:

• Randomized controlled, adaptive, open label clinical trial
  • 6 countries | 28 hospitals
• Participants
  • Adults admitted to the hospital with COVID-19 (between May 2020 and April 2021)
  • Moderately ill: Admission to hospital but not ICU | Not already mechanically ventilated | Not imminently requiring mechanical ventilation or critical care
  • Increased D-dimer levels
• Interventions
  • Therapeutic dose of heparin (dosing used for the treatment of venous thromboembolism)
  • Prophylactic dose heparin (protocols used for the prevention of venous thromboembolism)
  • Note: Heparin refers to either low molecular weight or unfractionated heparin
• Study design
  • Both groups continued intervention until they were discharged, day 28, or death
  • Outcomes were blindly adjudicated
• Primary outcome
  • Composite: Death | Invasive mechanical ventilation | Non-invasive mechanical ventilation | ICU admission
  • Assessed up to 28 days
• Secondary outcomes
  • All cause death
  • A composite of all cause death or any mechanical ventilation
  • Venous thromboembolism
• Safety outcomes
  • Major bleeding

RESULTS:

• Therapeutic dose: 228 participants | Prophylactic dose: 237 participants
  • Mean age 60 years
  • 56.8% men
  • Mean BMI 30.3 kg/m2
• No significant difference in incidence of the primary composite outcome between the two groups
  • Therapeutic: 16.2%
  • Prophylactic: 21.9%
  • Odds ratio 0.69 (95% CI, 0.43 to 1.10); P=0.12
• Deaths occurred in fewer patients in the therapeutic heparin group
  • Therapeutic: 1.8%
  • Prophylactic: 7.6%
  • OR 0.22 (95% CI, 0.07 to 0.65); P=0.006
• There was no significant difference in
  • The composite of all cause death or any mechanical ventilation
    • Therapeutic: 10.1%
    • Prophylactic: 16.0%
    • OR 0.59 (95% CI, 0.34 to 1.02); P=0.06
  • Venous thromboembolism
    • Therapeutic: 0.9%
    • Prophylactic: 2.5%
    • OR 0.34 (95% CI, 0.07 to 1.71); P=0.1
• There was no difference in major bleeding incidents between the two groups
  • Therapeutic: 0.9%
  • Prophylactic: 1.7%
  • OR 0.52 (95% CI, 0.09 to 2.85); P=0.69

CONCLUSION:

• There was no significant difference in the primary composite outcome among moderately ill COVID-19 patients who received either therapeutic or prophylactic doses of heparin
• Mortality was significantly decreased in the therapeutic heparin group by 78%
• There was a low risk of major bleeding in both groups
• The authors state

…given variation in findings from published trials, prospective meta-analyses will be important to determine the effects of different types and doses of anticoagulants in different patient subgroups

Learn More – Primary Sources:

Effectiveness of therapeutic heparin versus prophylactic heparin on death, mechanical ventilation, or intensive care unit admission in moderately ill patients with covid-19 admitted to hospital: RAPID randomised clinical trial

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