Randomized trials of therapeutic heparin for COVID-19: A meta-analysis.

COVID‐19 anticoagulation clinical trials heparin meta‐analysis

Journal

Research and practice in thrombosis and haemostasis
ISSN: 2475-0379
Titre abrégé: Res Pract Thromb Haemost
Pays: United States
ID NLM: 101703775

Informations de publication

Date de publication:
Dec 2021
Historique:
received: 13 10 2021
revised: 09 11 2021
accepted: 17 11 2021
entrez: 3 1 2022
pubmed: 4 1 2022
medline: 4 1 2022
Statut: epublish

Résumé

Pulmonary endothelial injury and microcirculatory thromboses likely contribute to hypoxemic respiratory failure, the most common cause of death, in patients with COVID-19. Randomized controlled trials (RCTs) suggest differences in the effect of therapeutic heparin between moderately and severely ill patients with COVID-19. We did a systematic review and meta-analysis of RCTs to determine the effects of therapeutic heparin in hospitalized patients with COVID-19. We searched PubMed, Embase, Web of Science, medRxiv, and medical conference proceedings for RCTs comparing therapeutic heparin with usual care, excluding trials that used oral anticoagulation or intermediate doses of heparin in the experimental arm. Mantel-Haenszel fixed-effect meta-analysis was used to combine odds ratios (ORs). There were 3 RCTs that compared therapeutic heparin to lower doses of heparin in 2854 moderately ill ward patients, and 3 RCTs in 1191 severely ill patients receiving critical care. In moderately ill patients, there was a nonsignificant reduction in all-cause death (OR, 0.76; 95% CI, 0.57-1.02), but significant reductions in the composite of death or invasive mechanical ventilation (OR, 0.77; 95% CI, 0.60 0.98), and death or any thrombotic event (OR, 0.58; 95% CI, 0.45-0.77). Organ support-free days alive (OR, 1.29; 95% CI, 1.07-1.57) were significantly increased with therapeutic heparin. There was a nonsignificant increase in major bleeding. In severely ill patients, there was no evidence for benefit of therapeutic heparin, with significant treatment-by-subgroup interactions with illness severity for all-cause death (

Sections du résumé

BACKGROUND BACKGROUND
Pulmonary endothelial injury and microcirculatory thromboses likely contribute to hypoxemic respiratory failure, the most common cause of death, in patients with COVID-19. Randomized controlled trials (RCTs) suggest differences in the effect of therapeutic heparin between moderately and severely ill patients with COVID-19. We did a systematic review and meta-analysis of RCTs to determine the effects of therapeutic heparin in hospitalized patients with COVID-19.
METHODS METHODS
We searched PubMed, Embase, Web of Science, medRxiv, and medical conference proceedings for RCTs comparing therapeutic heparin with usual care, excluding trials that used oral anticoagulation or intermediate doses of heparin in the experimental arm. Mantel-Haenszel fixed-effect meta-analysis was used to combine odds ratios (ORs).
RESULTS AND CONCLUSIONS CONCLUSIONS
There were 3 RCTs that compared therapeutic heparin to lower doses of heparin in 2854 moderately ill ward patients, and 3 RCTs in 1191 severely ill patients receiving critical care. In moderately ill patients, there was a nonsignificant reduction in all-cause death (OR, 0.76; 95% CI, 0.57-1.02), but significant reductions in the composite of death or invasive mechanical ventilation (OR, 0.77; 95% CI, 0.60 0.98), and death or any thrombotic event (OR, 0.58; 95% CI, 0.45-0.77). Organ support-free days alive (OR, 1.29; 95% CI, 1.07-1.57) were significantly increased with therapeutic heparin. There was a nonsignificant increase in major bleeding. In severely ill patients, there was no evidence for benefit of therapeutic heparin, with significant treatment-by-subgroup interactions with illness severity for all-cause death (

Identifiants

pubmed: 34977448
doi: 10.1002/rth2.12638
pii: S2475-0379(22)01494-7
pmc: PMC8681879
doi:

Types de publication

Journal Article

Langues

eng

Pagination

e12638

Informations de copyright

© 2021 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).

Références

N Engl J Med. 2021 Apr 22;384(16):1491-1502
pubmed: 33631065
N Engl J Med. 2021 Feb 11;384(6):497-511
pubmed: 33264556
BMJ. 2021 Mar 29;372:n71
pubmed: 33782057
ISRN Pharmacol. 2013 Jul 30;2013:910743
pubmed: 23984092
Lancet Rheumatol. 2020 Jul;2(7):e437-e445
pubmed: 32835247
BMJ. 2019 Aug 28;366:l4898
pubmed: 31462531
Thromb Haemost. 2021 Dec;121(12):1684-1695
pubmed: 33823560
Thromb Res. 2020 Dec;196:638-640
pubmed: 33066998
J Am Coll Cardiol. 2020 Jul 7;76(1):122-124
pubmed: 32387623
N Engl J Med. 2021 Aug 26;385(9):790-802
pubmed: 34351721
Crit Care Med. 2020 Sep;48(9):1358-1364
pubmed: 32467443
Lancet. 2020 Mar 28;395(10229):1054-1062
pubmed: 32171076
Eur Heart J. 2014 Dec 14;35(47):3336-45
pubmed: 25416325
J Thromb Haemost. 2020 Nov;18(11):2958-2967
pubmed: 32888372
BMJ. 2021 Oct 14;375:n2400
pubmed: 34649864
Cell. 2020 Nov 12;183(4):1043-1057.e15
pubmed: 32970989
Thromb Haemost. 2020 Dec;120(12):1700-1715
pubmed: 33368089
EBioMedicine. 2020 Sep;59:102969
pubmed: 32853989
N Engl J Med. 2021 Aug 26;385(9):777-789
pubmed: 34351722
Eur Heart J Cardiovasc Pharmacother. 2021 Sep 14;:
pubmed: 34519777
Chest. 2021 Oct;160(4):1471-1480
pubmed: 34153340
J Thromb Haemost. 2021 Sep;19(9):2225-2234
pubmed: 34236768
Clin Trials. 2020 Oct;17(5):491-500
pubmed: 32815416
JAMA Intern Med. 2021 Dec 1;181(12):1612-1620
pubmed: 34617959
Trials. 2021 Mar 10;22(1):202
pubmed: 33691765
JAMA. 2021 Apr 27;325(16):1620-1630
pubmed: 33734299
J Thromb Haemost. 2020 May;18(5):1094-1099
pubmed: 32220112
Lancet. 2021 Jun 12;397(10291):2253-2263
pubmed: 34097856
N Engl J Med. 2021 Aug 26;385(9):845-846
pubmed: 34347948
J Thromb Haemost. 2005 Apr;3(4):692-4
pubmed: 15842354
Thromb Res. 2020 Dec;196:359-366
pubmed: 32977137
Res Pract Thromb Haemost. 2020 Sep 25;:
pubmed: 33043231

Auteurs

Michelle Sholzberg (M)

Department of Medicine St. Michael's Hospital Li Ka Shing Knowledge Institute University of Toronto Toronto ON Canada.
Department of Laboratory Medicine and Pathobiology St. Michael's Hospital Li Ka Shing Knowledge Institute University of Toronto Toronto ON Canada.

Bruno R da Costa (BR)

Applied Health Research Centre (AHRC) St. Michael's Hospital Li Ka Shing Knowledge Institute University of Toronto Toronto ON Canada.
Institute of Primary Health Care (BIHAM) University of Bern Bern Switzerland.

Grace H Tang (GH)

Hematology-Oncology Clinical Research Group St. Michael's Hospital University of Toronto Toronto ON Canada.

Hassan Rahhal (H)

Disciplina de Emergencias Clinicas Departamento de Clinica Medica Hospital das Clinicas HCFMUSP Faculdade de Medicina Universidade de Sao Paulo Sao Paulo Brazil.

Musaad AlHamzah (M)

Department of Surgery College of Medicine King Saud University Riyadh Saudi Arabia.
Division of Vascular Surgery King Saud University Medical City Riyadh Saudi Arabia.

Lisa Baumann Kreuziger (L)

Versiti Medical College of Wisconsin Milwaukee Wisconsin USA.

Fionnuala Ní Áinle (F)

Mater Misericordiae University Hospital Dublin Ireland.
School of Medicine University College Dublin Dublin Ireland.
Irish Network for Venous Thromboembolism Research Dublin Ireland.

Mozah Obaid Almarshoodi (MO)

Tawam Hospital SEHA AlAin United Arab Emirates.

Paula D James (PD)

Department of Medicine Queen's University Kingston ON Canada.

David Lillicrap (D)

Department of Pathology and Molecular Medicine Queen's University Kingston ON Canada.

Marc Carrier (M)

Department of Medicine The Ottawa Hospital Research Institute at the University of Ottawa Ottawa ON Canada.

Andrew Beckett (A)

St. Michael's Hospital University of Toronto Toronto ON Canada.
Canadian Forces Health Services Ottawa ON Canada.

Michael Fralick (M)

General Internal Medicine Sinai Health University of Toronto Toronto ON Canada.

Saskia Middeldorp (S)

Department of Internal Medicine Radboud Institute of Health Sciences (RIHS) Radboud University Medical Center Nijmegen The Netherlands.

Agnes Y Y Lee (AYY)

Vancouver Coastal Health Research Institute University of British Columbia Vancouver BC Canada.

Kevin E Thorpe (KE)

Dalla Lana School of Public Health Applied Health Research Centre St. Michael's Hospital Li Ka Shing Knowledge Institute University of Toronto Toronto ON Canada.

Elnara Márcia Negri (EM)

Laboratorio de Investigaçao Medica LIM-59 Biologia Celular Departamento de Patologia Faculdade de Medicina da Universidade de São Paulo São Paulo Brazil.

Mary Cushman (M)

Department of Medicine Larner College of Medicine at the University of Vermont University of Vermont Medical Center Burlington Vermont USA.

Peter Jüni (P)

Department of Medicine Institute of Health Policy, Management and Evaluation Applied Health Research Centre St. Michael's Hospital Li Ka Shing Knowledge Institute University of Toronto Toronto ON Canada.

Classifications MeSH