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Therapeutic anticoagulation with heparin in noncritically Ill patients with Covid-19

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Title: Therapeutic anticoagulation with heparin in noncritically Ill patients with Covid-19
Authors: The ATTACC, ACTIV-4a, and REMAP-CAP Investigators
Item Type: Journal Article
Abstract: BACKGROUND Thrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19. METHODS In this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care–level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis. The primary outcome was organ support–free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of −1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline d-dimer level. RESULTS The trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met. Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support–free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58). The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2). The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high d-dimer cohort, 92.9% in the low d-dimer cohort, and 97.3% in the unknown d-dimer cohort. Major bleeding occurred in 1.9% of the patients receiving therapeutic-dose anticoagulation and in 0.9% of those receiving thromboprophylaxis. CONCLUSIONS In noncritically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support as compared with usual-care thromboprophylaxis. (ATTACC, ACTIV-4a, and REMAP-CAP ClinicalTrials.gov numbers, NCT04372589. opens in new tab, NCT04505774. opens in new tab, NCT02735707. opens in new tab, and NCT04359277. opens in new tab.)
Issue Date: 26-Aug-2021
Date of Acceptance: 1-Aug-2021
URI: http://hdl.handle.net/10044/1/90873
DOI: 10.1056/nejmoa2105911
ISSN: 0028-4793
Publisher: Massachusetts Medical Society
Start Page: 790
End Page: 802
Journal / Book Title: New England Journal of Medicine
Volume: 385
Copyright Statement: © 2021 Massachusetts Medical Society. All rights reserved.
Sponsor/Funder: NIHR
National Institute for Health Research
Funder's Grant Number: COVID-19-REMAP-CAP
Keywords: Science & Technology
Life Sciences & Biomedicine
Medicine, General & Internal
General & Internal Medicine
Adult
Aged
Anticoagulants
COVID-19
Female
Hemorrhage
Heparin
Heparin, Low-Molecular-Weight
Hospital Mortality
Humans
Male
Middle Aged
Survival Analysis
Thrombosis
ATTACC Investigators
ACTIV-4a Investigators
REMAP-CAP Investigators
Humans
Thrombosis
Hemorrhage
Heparin
Heparin, Low-Molecular-Weight
Anticoagulants
Hospital Mortality
Survival Analysis
Adult
Aged
Middle Aged
Female
Male
COVID-19
11 Medical and Health Sciences
General & Internal Medicine
Publication Status: Published
Embargo Date: 2022-02-01
Article Number: NEJMoa2105911
Online Publication Date: 2021-08-26
Appears in Collections:Department of Immunology and Inflammation
Department of Surgery and Cancer
National Heart and Lung Institute
Faculty of Medicine
Imperial College London COVID-19