Therapeutic Anticoagulation vs. Usual Care in Critically Ill Patients With COVID-19 - REMAP-CAP, ACTIV-4a, and ATTACC

Contribution To Literature:

This multiplatform trial failed to show that therapeutic anticoagulation improved outcomes compared with usual care in critically ill patients with COVID-19 infection.

Description:

The goal of the trial was to evaluate therapeutic anticoagulation with heparin compared with usual care among critically ill patients with coronavirus disease 2019 (COVID-19) infection.

Study Design

  • Randomized
  • Parallel
  • Open-label
  • Multiplatform: To enhance power, three similarly designed trials were pooled: REMAP-CAP (Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia), ACTIV-4a (A Multicenter, Adaptive, Randomized Controlled Platform Trial of the Safety and Efficacy of Antithrombotic Strategies in Hospitalized Adults With COVID-19), and ATTACC (Antithrombotic Therapy to Ameliorate Complications of COVID-19).

Critically ill patients with COVID-19 infection were randomized to therapeutic anticoagulation (n = 591) versus usual care (n = 616).

  • Total number of enrollees: 1,207
  • Duration of follow-up: 21 days
  • Mean patient age: 60 years
  • Percentage female: 28%
  • Percentage with diabetes: 32%

Inclusion criteria:

  • Patients with COVID-19 infection requiring respiratory or cardiovascular organ intensive care unit (ICU) support

Exclusion criteria:

  • Imminent risk for death
  • Sensitivity to heparin
  • High risk for bleeding, receiving dual antiplatelet therapy, or indication for therapeutic anticoagulation

Principal Findings:

The primary outcome, median organ support–free days, was 1 in the therapeutic anticoagulation group compared with 4 in the usual care group (probability of superiority = 5%, probability of futility = 99.9%, probability of inferiority = 95.0%).

Secondary outcomes:

  • Survival to hospital discharge: 62.7% in the therapeutic anticoagulation group compared with 64.5% in the usual care group (probability of inferiority = 89.2%)
  • Death or major thrombotic event: 40.1% in the therapeutic anticoagulation group compared with 41.1% in the usual care group (probability of inferiority = 59.7%)
  • Major bleeding: 3.8% in the therapeutic anticoagulation group compared with 2.3% in the usual care group (probability of inferiority = 87.2%)

Interpretation:

Among critically ill patients with COVID-19 infection, therapeutic anticoagulation with heparin did not improve survival or organ support–free days. In fact, therapeutic anticoagulation was associated with a 95% probability of inferiority compared with usual care. The mechanism for the likely harm from therapeutic anticoagulation is uncertain, although potentially could cause bleeding at a microvascular level, resulting in worsening pulmonary alveolar hemorrhage.

References:

The REMAP-CAP, ACTIV-4a, and ATTACC Investigators. Therapeutic Anticoagulation With Heparin in Critically Ill Patients With Covid-19. N Engl J Med 2021;Aug 4:[Epub ahead of print].

Editorial: ten Cate H. Surviving Covid-19 With Heparin? N Engl J Med 2021;Aug 4:[Epub ahead of print].

Clinical Topics: Anticoagulation Management, Cardiovascular Care Team, Prevention

Keywords: Anticoagulants, Blood Coagulation, Coronavirus Infections, COVID-19, Critical Illness, Fibrinolytic Agents, Hemorrhage, Heparin, Intensive Care Units, Medical Futility, Patient Discharge, Primary Prevention, Respiration, Artificial, Thrombosis, Vascular Diseases


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