Open AccessTherapeutic anticoagulation to prevent thrombosis, coagulopathy, and mortality in severe COVID‐19: The Swiss COVID‐HEP randomized clinical trial
Author(s) -
Blondon Marc,
Cereghetti Sara,
Pugin Jérôme,
Marti Christophe,
Darbellay Farhoumand Pauline,
Reny JeanLuc,
Calmy Alexandra,
Combescure Christophe,
Mazzolai Lucia,
Pantet Olivier,
Ltaief Zied,
Méan Marie,
Manzocchi Besson Sara,
Jeanneret Séverin,
Stricker Hans,
RobertEbadi Helia,
Fontana Pierre,
Righini Marc,
Casini Alessandro
Publication year - 2022
Publication title -
research and practice in thrombosis and haemostasis
Language(s) - English
Resource type - Journals
ISSN - 2475-0379
DOI - 10.1002/rth2.12712
Subject(s) - medicine , pulmonary embolism , coagulopathy , randomized controlled trial , deep vein , asymptomatic , thrombosis , hazard ratio , confidence interval
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.