Therapeutic anticoagulation to prevent thrombosis, coagulopathy, and mortality in severe COVID‐19: The Swiss COVID‐HEP randomized clinical trial
Abstract Background Hospitalized patients with COVID‐19 suffered initially from high rates of venous thromboembolism (VTE), with possible associations between therapeutic anticoagulation and better clinical outcomes in observational studies. Objective To test whether therapeutic anticoagulation impr...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-05-01
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| Series: | Research and Practice in Thrombosis and Haemostasis |
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| Online Access: | https://doi.org/10.1002/rth2.12712 |
| _version_ | 1797760877238157312 |
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| author | Marc Blondon Sara Cereghetti Jérôme Pugin Christophe Marti Pauline Darbellay Farhoumand Jean‐Luc Reny Alexandra Calmy Christophe Combescure Lucia Mazzolai Olivier Pantet Zied Ltaief Marie Méan Sara Manzocchi Besson Séverin Jeanneret Hans Stricker Helia Robert‐Ebadi Pierre Fontana Marc Righini Alessandro Casini |
| author_facet | Marc Blondon Sara Cereghetti Jérôme Pugin Christophe Marti Pauline Darbellay Farhoumand Jean‐Luc Reny Alexandra Calmy Christophe Combescure Lucia Mazzolai Olivier Pantet Zied Ltaief Marie Méan Sara Manzocchi Besson Séverin Jeanneret Hans Stricker Helia Robert‐Ebadi Pierre Fontana Marc Righini Alessandro Casini |
| author_sort | Marc Blondon |
| collection | DOAJ |
| description | Abstract Background Hospitalized patients with COVID‐19 suffered initially from high rates of venous thromboembolism (VTE), with possible associations between therapeutic anticoagulation and better clinical outcomes in observational studies. Objective To test whether therapeutic anticoagulation improves clinical outcomes in severe COVID‐19. Patients/Methods In this multicenter, open‐label, randomized controlled trial, we recruited acutely ill medical COVID‐19 patients with D‐dimer >1000 ng/ml or critically ill COVID‐19 patients in four Swiss hospitals, from April 2020 until June 2021, with a 30‐day follow‐up. Participants were randomized to in‐hospital therapeutic anticoagulation versus low‐dose anticoagulation in acutely ill participants/intermediate‐dose anticoagulation in critically ill participants, with enoxaparin or unfractionated heparins. The primary outcome was a centrally adjudicated composite of 30‐day all‐cause mortality, VTE, arterial thrombosis, and disseminated intravascular coagulopathy (DIC), with screening for proximal deep vein thrombosis. Results Among 159 participants, 55.3% were critically ill and 94.3% received corticosteroids. Before study inclusion, pulmonary embolism had been excluded in 71.7%. The primary outcome occurred in 4/79 participants randomized to therapeutic anticoagulation and 4/80 to low/intermediate anticoagulation (5.4% vs. 5.0%; risk difference +0.4%; adjusted hazard ratio 0.76, 95% confidence interval 0.18–3.21), including three deaths in each group. All primary outcomes and major bleeding (n = 3) occurred in critically ill participants. There was no asymptomatic proximal deep vein thrombosis and no difference in major bleeding. Conclusions Among patients with severe COVID‐19 treated with corticosteroids and with exclusion of pulmonary embolism at hospital admission for most, risks of mortality, thrombotic outcomes, and DIC were low at 30 days. The lack of benefit of therapeutic anticoagulation was too imprecise for definite conclusions. |
| first_indexed | 2024-03-12T19:04:52Z |
| format | Article |
| id | doaj.art-0b7ac534371343c3bb2a965f1d443a36 |
| institution | Directory Open Access Journal |
| issn | 2475-0379 |
| language | English |
| last_indexed | 2024-03-12T19:04:52Z |
| publishDate | 2022-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Research and Practice in Thrombosis and Haemostasis |
| spelling | doaj.art-0b7ac534371343c3bb2a965f1d443a362023-08-02T06:18:17ZengElsevierResearch and Practice in Thrombosis and Haemostasis2475-03792022-05-0164n/an/a10.1002/rth2.12712Therapeutic anticoagulation to prevent thrombosis, coagulopathy, and mortality in severe COVID‐19: The Swiss COVID‐HEP randomized clinical trialMarc Blondon0Sara Cereghetti1Jérôme Pugin2Christophe Marti3Pauline Darbellay Farhoumand4Jean‐Luc Reny5Alexandra Calmy6Christophe Combescure7Lucia Mazzolai8Olivier Pantet9Zied Ltaief10Marie Méan11Sara Manzocchi Besson12Séverin Jeanneret13Hans Stricker14Helia Robert‐Ebadi15Pierre Fontana16Marc Righini17Alessandro Casini18Division of Angiology and Hemostasis Geneva University Hospitals and Faculty of Medicine Geneva SwitzerlandDivision of Intensive Care Geneva University Hospitals and Faculty of Medicine Geneva SwitzerlandDivision of Intensive Care Geneva University Hospitals and Faculty of Medicine Geneva SwitzerlandDivision of General Internal Medicine Geneva University Hospitals and Faculty of Medicine Geneva SwitzerlandDivision of General Internal Medicine Geneva University Hospitals and Faculty of Medicine Geneva SwitzerlandDivision of General Internal Medicine Geneva University Hospitals and Faculty of Medicine Geneva SwitzerlandHIV/AIDS Unit Division of Infectious Disease Geneva University Hospitals and Faculty of Medicine Geneva SwitzerlandClinical Research Center Geneva University Hospitals and Faculty of Medicine Geneva SwitzerlandDivision of Angiology Centre Hospitalier Universitaire Vaudois Lausanne SwitzerlandDivision of Intensive Care Centre Hospitalier Universitaire Vaudois Lausanne SwitzerlandDivision of Intensive Care Centre Hospitalier Universitaire Vaudois Lausanne SwitzerlandDivision of Internal Medicine Centre Hospitalier Universitaire Vaudois Lausanne SwitzerlandUnit of Angiology Hôpital du Valais Sion SwitzerlandDivision of Intensive Care Hôpital du Valais Sion SwitzerlandDivision of Angiology Locarno Regional Hospital Locarno SwitzerlandDivision of Angiology and Hemostasis Geneva University Hospitals and Faculty of Medicine Geneva SwitzerlandDivision of Angiology and Hemostasis Geneva University Hospitals and Faculty of Medicine Geneva SwitzerlandDivision of Angiology and Hemostasis Geneva University Hospitals and Faculty of Medicine Geneva SwitzerlandDivision of Angiology and Hemostasis Geneva University Hospitals and Faculty of Medicine Geneva SwitzerlandAbstract Background Hospitalized patients with COVID‐19 suffered initially from high rates of venous thromboembolism (VTE), with possible associations between therapeutic anticoagulation and better clinical outcomes in observational studies. Objective To test whether therapeutic anticoagulation improves clinical outcomes in severe COVID‐19. Patients/Methods In this multicenter, open‐label, randomized controlled trial, we recruited acutely ill medical COVID‐19 patients with D‐dimer >1000 ng/ml or critically ill COVID‐19 patients in four Swiss hospitals, from April 2020 until June 2021, with a 30‐day follow‐up. Participants were randomized to in‐hospital therapeutic anticoagulation versus low‐dose anticoagulation in acutely ill participants/intermediate‐dose anticoagulation in critically ill participants, with enoxaparin or unfractionated heparins. The primary outcome was a centrally adjudicated composite of 30‐day all‐cause mortality, VTE, arterial thrombosis, and disseminated intravascular coagulopathy (DIC), with screening for proximal deep vein thrombosis. Results Among 159 participants, 55.3% were critically ill and 94.3% received corticosteroids. Before study inclusion, pulmonary embolism had been excluded in 71.7%. The primary outcome occurred in 4/79 participants randomized to therapeutic anticoagulation and 4/80 to low/intermediate anticoagulation (5.4% vs. 5.0%; risk difference +0.4%; adjusted hazard ratio 0.76, 95% confidence interval 0.18–3.21), including three deaths in each group. All primary outcomes and major bleeding (n = 3) occurred in critically ill participants. There was no asymptomatic proximal deep vein thrombosis and no difference in major bleeding. Conclusions Among patients with severe COVID‐19 treated with corticosteroids and with exclusion of pulmonary embolism at hospital admission for most, risks of mortality, thrombotic outcomes, and DIC were low at 30 days. The lack of benefit of therapeutic anticoagulation was too imprecise for definite conclusions.https://doi.org/10.1002/rth2.12712anticoagulantsCOVID‐19heparinrandomized controlled trialthrombosis |
| spellingShingle | Marc Blondon Sara Cereghetti Jérôme Pugin Christophe Marti Pauline Darbellay Farhoumand Jean‐Luc Reny Alexandra Calmy Christophe Combescure Lucia Mazzolai Olivier Pantet Zied Ltaief Marie Méan Sara Manzocchi Besson Séverin Jeanneret Hans Stricker Helia Robert‐Ebadi Pierre Fontana Marc Righini Alessandro Casini Therapeutic anticoagulation to prevent thrombosis, coagulopathy, and mortality in severe COVID‐19: The Swiss COVID‐HEP randomized clinical trial Research and Practice in Thrombosis and Haemostasis anticoagulants COVID‐19 heparin randomized controlled trial thrombosis |
| title | Therapeutic anticoagulation to prevent thrombosis, coagulopathy, and mortality in severe COVID‐19: The Swiss COVID‐HEP randomized clinical trial |
| title_full | Therapeutic anticoagulation to prevent thrombosis, coagulopathy, and mortality in severe COVID‐19: The Swiss COVID‐HEP randomized clinical trial |
| title_fullStr | Therapeutic anticoagulation to prevent thrombosis, coagulopathy, and mortality in severe COVID‐19: The Swiss COVID‐HEP randomized clinical trial |
| title_full_unstemmed | Therapeutic anticoagulation to prevent thrombosis, coagulopathy, and mortality in severe COVID‐19: The Swiss COVID‐HEP randomized clinical trial |
| title_short | Therapeutic anticoagulation to prevent thrombosis, coagulopathy, and mortality in severe COVID‐19: The Swiss COVID‐HEP randomized clinical trial |
| title_sort | therapeutic anticoagulation to prevent thrombosis coagulopathy and mortality in severe covid 19 the swiss covid hep randomized clinical trial |
| topic | anticoagulants COVID‐19 heparin randomized controlled trial thrombosis |
| url | https://doi.org/10.1002/rth2.12712 |
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