Randomized trials of therapeutic heparin for COVID‐19: A meta‐analysis
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 moderat...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-12-01
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| Series: | Research and Practice in Thrombosis and Haemostasis |
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| Online Access: | https://doi.org/10.1002/rth2.12638 |
| _version_ | 1797707218579095552 |
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| author | Michelle Sholzberg Bruno R. daCosta Grace H. Tang Hassan Rahhal Musaad AlHamzah Lisa Baumann Kreuziger Fionnuala Ní Áinle Mozah Obaid Almarshoodi Paula D. James David Lillicrap Marc Carrier Andrew Beckett Michael Fralick Saskia Middeldorp Agnes Y. Y. Lee Kevin E. Thorpe Elnara Márcia Negri Mary Cushman Peter Jüni the RAPID Trial Investigators |
| author_facet | Michelle Sholzberg Bruno R. daCosta Grace H. Tang Hassan Rahhal Musaad AlHamzah Lisa Baumann Kreuziger Fionnuala Ní Áinle Mozah Obaid Almarshoodi Paula D. James David Lillicrap Marc Carrier Andrew Beckett Michael Fralick Saskia Middeldorp Agnes Y. Y. Lee Kevin E. Thorpe Elnara Márcia Negri Mary Cushman Peter Jüni the RAPID Trial Investigators |
| author_sort | Michelle Sholzberg |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T06:04:06Z |
| format | Article |
| id | doaj.art-c3f933cd78734864812d556a34871b11 |
| institution | Directory Open Access Journal |
| issn | 2475-0379 |
| language | English |
| last_indexed | 2024-03-12T06:04:06Z |
| publishDate | 2021-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Research and Practice in Thrombosis and Haemostasis |
| spelling | doaj.art-c3f933cd78734864812d556a34871b112023-09-03T03:52:09ZengElsevierResearch and Practice in Thrombosis and Haemostasis2475-03792021-12-0158n/an/a10.1002/rth2.12638Randomized trials of therapeutic heparin for COVID‐19: A meta‐analysisMichelle Sholzberg0Bruno R. daCosta1Grace H. Tang2Hassan Rahhal3Musaad AlHamzah4Lisa Baumann Kreuziger5Fionnuala Ní Áinle6Mozah Obaid Almarshoodi7Paula D. James8David Lillicrap9Marc Carrier10Andrew Beckett11Michael Fralick12Saskia Middeldorp13Agnes Y. Y. Lee14Kevin E. Thorpe15Elnara Márcia Negri16Mary Cushman17Peter Jüni18the RAPID Trial InvestigatorsDepartment of Medicine St. Michael’s Hospital Li Ka Shing Knowledge Institute University of Toronto Toronto ON CanadaApplied Health Research Centre (AHRC) St. Michael’s Hospital Li Ka Shing Knowledge Institute University of Toronto Toronto ON CanadaHematology‐Oncology Clinical Research Group St. Michael's Hospital University of Toronto Toronto ON CanadaDisciplina de Emergencias Clinicas Departamento de Clinica Medica Hospital das Clinicas HCFMUSP Faculdade de Medicina Universidade de Sao Paulo Sao Paulo BrazilDepartment of Surgery College of Medicine King Saud University Riyadh Saudi ArabiaVersiti Medical College of Wisconsin Milwaukee Wisconsin USAMater Misericordiae University Hospital Dublin IrelandTawam Hospital SEHA AlAin United Arab EmiratesDepartment of Medicine Queen’s University Kingston ON CanadaDepartment of Pathology and Molecular Medicine Queen's University Kingston ON CanadaDepartment of Medicine The Ottawa Hospital Research Institute at the University of Ottawa Ottawa ON CanadaSt. Michael’s Hospital University of Toronto Toronto ON CanadaGeneral Internal Medicine Sinai Health University of Toronto Toronto ON CanadaDepartment of Internal Medicine Radboud Institute of Health Sciences (RIHS) Radboud University Medical Center Nijmegen The NetherlandsVancouver Coastal Health Research Institute University of British Columbia Vancouver BC CanadaDalla Lana School of Public Health Applied Health Research Centre St. Michael’s Hospital Li Ka Shing Knowledge Institute University of Toronto Toronto ON CanadaLaboratorio de Investigaçao Medica LIM‐59 Biologia Celular Departamento de Patologia Faculdade de Medicina da Universidade de São Paulo São Paulo BrazilDepartment of Medicine Larner College of Medicine at the University of Vermont University of Vermont Medical Center Burlington Vermont USADepartment 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 CanadaAbstract 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.https://doi.org/10.1002/rth2.12638anticoagulationclinical trialsCOVID‐19heparinmeta‐analysis |
| spellingShingle | Michelle Sholzberg Bruno R. daCosta Grace H. Tang Hassan Rahhal Musaad AlHamzah Lisa Baumann Kreuziger Fionnuala Ní Áinle Mozah Obaid Almarshoodi Paula D. James David Lillicrap Marc Carrier Andrew Beckett Michael Fralick Saskia Middeldorp Agnes Y. Y. Lee Kevin E. Thorpe Elnara Márcia Negri Mary Cushman Peter Jüni the RAPID Trial Investigators Randomized trials of therapeutic heparin for COVID‐19: A meta‐analysis Research and Practice in Thrombosis and Haemostasis anticoagulation clinical trials COVID‐19 heparin meta‐analysis |
| title | Randomized trials of therapeutic heparin for COVID‐19: A meta‐analysis |
| title_full | Randomized trials of therapeutic heparin for COVID‐19: A meta‐analysis |
| title_fullStr | Randomized trials of therapeutic heparin for COVID‐19: A meta‐analysis |
| title_full_unstemmed | Randomized trials of therapeutic heparin for COVID‐19: A meta‐analysis |
| title_short | Randomized trials of therapeutic heparin for COVID‐19: A meta‐analysis |
| title_sort | randomized trials of therapeutic heparin for covid 19 a meta analysis |
| topic | anticoagulation clinical trials COVID‐19 heparin meta‐analysis |
| url | https://doi.org/10.1002/rth2.12638 |
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