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

Aug 16, 2021
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Date Published:
08/04/2021
Date Updated:
08/16/2021
Original Posted Date:
08/16/2021
References

Contribution To Literature:

This multiplatform trial showed that therapeutic anticoagulation improved outcomes compared with usual care in noncritically ill patients with COVID-19 infection.

Description:

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

Study Design

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

Noncritically ill patients with COVID-19 infection were randomized to therapeutic anticoagulation (n = 1,190) versus usual care (n = 1,054).

  • Total number of enrollees: 2,244
  • Duration of follow-up: 21 days
  • Mean patient age: 59 years
  • Percentage female: 40%
  • Percentage with diabetes: 30%

Inclusion criteria:

  • Patients with COVID-19 infection not requiring respiratory or cardiovascular organ intensive care unit support

Exclusion criteria:

  • Hospital discharge expected within 72 hours
  • Sensitivity to heparin
  • High risk for bleeding, receiving dual antiplatelet therapy, or indication for therapeutic anticoagulation

Principal Findings:

The primary outcome, proportion of patients who survived until hospital discharge without need for organ support, was 80.2% in the therapeutic anticoagulation group compared with 76.4% in the usual care group (probability of superiority = 98.6%). Benefit was observed regardless of the baseline D-dimer level.

Secondary outcomes:

  • Survival to hospital discharge: 92.7% in the therapeutic anticoagulation group compared with 91.8% in the usual care group (probability of superiority = 87.1%)
  • Death or major thrombotic event: 8.0% in the therapeutic anticoagulation group compared with 9.9% in the usual care group (probability of superiority = 98.0%)
  • Major bleeding: 1.9% in the therapeutic anticoagulation group compared with 0.9% in the usual care group (probability of inferiority = 95.5%)

Interpretation:

Among noncritically ill patients with COVID-19 infection, therapeutic anticoagulation with heparin improved the proportion of patients who survived without need for organ support. Therapeutic anticoagulation was associated with a 98.6% probability of superiority compared with usual care. Major bleeding was increased in the therapeutic anticoagulation group. These results contrast to therapeutic anticoagulation in COVID-19 patients with critical illness.

References:

The ATTACC, ACTIV-4a, and REMAP-CAP Investigators. Therapeutic Anticoagulation With Heparin in Noncritically 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, COVID-19 Hub, Prevention

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


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