Therapeutic anticoagulation to prevent thrombosis, coagulopathy, and mortality in severe COVID‐19: The Swiss COVID‐HEP randomized clinical trial
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
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: = 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.