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

Research and Practice in Thrombosis and Haemostasis

the RAPID Trial Investigators¹  Bruno R. daCosta²  Kevin E. Thorpe³  Saskia Middeldorp⁴  Peter Jüni⁵  Mary Cushman⁶  Paula D. James⁷  Michelle Sholzberg⁸  Marc Carrier⁹  David Lillicrap^1,10  Musaad AlHamzah^1,11  Hassan Rahhal^1,12  Michael Fralick^1,13  Grace H. Tang^1,14  Elnara Márcia Negri^1,15  Fionnuala Ní Áinle^1,16  Andrew Beckett^1,17  Mozah Obaid Almarshoodi^1,18  Agnes Y. Y. Lee^1,19  Lisa Baumann Kreuziger^2,20 

[1] ;Applied Health Research Centre (AHRC) St. Michael’s Hospital Li Ka Shing Knowledge Institute University of Toronto Toronto ON Canada;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;Department of Internal Medicine Radboud Institute of Health Sciences (RIHS) Radboud University Medical Center Nijmegen The Netherlands;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;Department of Medicine Larner College of Medicine at the University of Vermont University of Vermont Medical Center Burlington Vermont USA;Department of Medicine Queen’s University Kingston ON Canada;Department of Medicine St. Michael’s Hospital Li Ka Shing Knowledge Institute University of Toronto Toronto ON Canada;Department of Medicine The Ottawa Hospital Research Institute at the University of Ottawa Ottawa ON Canada;Department of Pathology and Molecular Medicine Queen's University Kingston ON Canada;Department of Surgery College of Medicine King Saud University Riyadh Saudi Arabia;Disciplina de Emergencias Clinicas Departamento de Clinica Medica Hospital das Clinicas HCFMUSP Faculdade de Medicina Universidade de Sao Paulo Sao Paulo Brazil;General Internal Medicine Sinai Health University of Toronto Toronto ON Canada;Hematology‐Oncology Clinical Research Group St. Michael's Hospital University of Toronto Toronto ON Canada;Laboratorio de Investigaçao Medica LIM‐59 Biologia Celular Departamento de Patologia Faculdade de Medicina da Universidade de São Paulo São Paulo Brazil;Mater Misericordiae University Hospital Dublin Ireland;St. Michael’s Hospital University of Toronto Toronto ON Canada;Tawam Hospital SEHA AlAin United Arab Emirates;Vancouver Coastal Health Research Institute University of British Columbia Vancouver BC Canada;Versiti Medical College of Wisconsin Milwaukee Wisconsin USA;

关键词: anticoagulation;    clinical trials;    COVID‐19;    heparin;    meta‐analysis;   

DOI  :  10.1002/rth2.12638

来源: DOAJ

【 摘 要 】

Abstract 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 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 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 (P = .034). In conclusion, therapeutic heparin is beneficial in moderately ill patients but not in severely ill patients hospitalized with COVID‐19.

【 授权许可】

Unknown