Journal
NEW ENGLAND JOURNAL OF MEDICINE
Volume 385, Issue 9, Pages 790-802Publisher
MASSACHUSETTS MEDICAL SOC
DOI: 10.1056/NEJMoa2105911
Keywords
-
Categories
Funding
- LifeArc Foundation, Thistledown Foundation, Research Manitoba
- Ontario Ministry of Health, Peter Munk Cardiac Centre
- CancerCare Manitoba Foundation
- Victoria General Hospital Foundation
- National Heart, Lung, and Blood Institute, National Institutes of Health (NIH) [OTA-20-011, 1OT2HL156812-01, UL1TR001445]
- New York University Clinical and Translational Science Award program
- National Center for Advancing Translational Sciences of the NIH
- European Union through FP7HEALTH-2013-INNOVATION: the Platform for European Preparedness Against (Re-)emerging Epidemics (PREPARE) consortium [602525]
- Horizon 2020 research and innovation program: the Rapid European Covid-19 Emergency Research response (RECOVER) consortium [101003589]
- Australian National Health and Medical Research Council [APP1101719, APP1116530]
- Health Research Council of New Zealand [16/631]
- Canadian Institutes of Health Research (Strategy for Patient-Oriented Research Innovative Clinical Trials Program) [158584, 447335]
- U.K. National Institute for Health Research (NIHR)
- NIHR Imperial Biomedical Research Centre
- Health Research Board of Ireland [CTN 2014-012]
- Breast Cancer Research Foundation
- French Ministry of Health [PHRC-20-0147]
- Minderoo Foundation
- Amgen
- Global Coalition for Adaptive Research
- Wellcome Trust [215522]
- Canadian Institutes of Health Research [AR7-162822]
- NIHR Research Professorship [RP-2015-06-18]
- NIHR Clinician Scientist Fellowship [CS-2016-16-011]
- Lyonel G. Israels Research Chair in Hematology (University of Manitoba)
- Health Research Board (HRB) [CTN-2014-012] Funding Source: Health Research Board (HRB)
Ask authors/readers for more resources
This study showed that therapeutic-dose anticoagulation with heparin in non-critically ill patients with Covid-19 increased the likelihood of survival to hospital discharge and reduced the need for cardiovascular or respiratory organ support compared to usual-care thromboprophylaxis.
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available