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Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19

Authors
Patrick Lawler,Ewan Goligher
Jeffrey Berger,Matthew Neal,Bryan McVerry,Stephen Wiviott,Michelle Gong,Marc Carrier,Rachael Parke,Harmony Reynolds,Alexis Turgeon,Jorge Escobedo,David Leaf,Charlotte Summers,Brett Houston,Lucy Kornblith,Anand Kumar,Susan Kahn,Mary Cushman,Zoe McQuilten,Arthur Slutsky,Keri Kim,Anthony Gordon,Bridget‐Anne Kirwan,Maria Brooks,Alisa Higgins,Roger Lewis,Elizabeth Lorenzi,Scott Berry,Lindsay Berry,Derek Russell,Farah Al-Beidh,Djillali Annane,Judith Marín‐Corral,Lisa Kreuziger,Aaron Aday,Zahra Bhimani,Shailesh Bihari,Henny Billett,Lindsay Bond,Marc Bonten,Abi Beane,Meredith Buxton,Lana Castellucci,Sweta Chekuri,Jen‐Ting Chen,Allen Cheng,Tamta Chkhikvadze,Benjamin Coiffard,Todd Costantini,Sophie Brouwer,Michelle Detry,Mark Effron,Lise Estcourt,Dean Fergusson,Mark Fitzgerald,Robert Fowler,J.‐P. Galanaud,Sheetal Gandotra,María Leciñana,Timothy Girard,Lucas Godoy,Andrew Goodman,Zhuxuan Fu,Yonatan Greenstein,Timo Tolppa,Naomi Hamburg,Rashan Haniffa,George Hanna,Cameron Green,Carolyn Hendrickson,R. Hite,Aluko Hope,Christopher Horvat,Kristin Hudock,Beverley Hunt,Mansoor Husain,Vivek Iyer,Jeffrey Jacobson,Yuri Kim,Andrei Kindzelski,Andrew King,M. Knudson,Aaron Kornblith,Akram Khan,Grégoire Gal,George Lim,Michael Laffan,François Lamontagne,López-Sendón Jl,Sylvain Lother,Felipe Lima,Miguel Marcos,Janet Ferrier,John Marshall,Nicole Marten,Michael Matthay,Daniel McAuley,Anna McGlothlin,Shay McGuinness,Saskia Middeldorp,Stephanie Montgomery,Daniel Harvey,Raquel Guerrero,Alistair Nichol,Brenda Nuñez-Garcia,Paul Mouncey,Srinivas Murthy,Jonathan Paul,Yazmín González,John Park,John Quigley,Sam Parnia,Jonathan Bannard‐Smith,Simone Piva,Christina Saunders,Kathryn Puxty,Christopher Seymour,Deborah Siegal,Delcio Silva,Manu Shankar‐Hari,John Sheehan,Aneesh Singhal,Dayna Solvason,Simon Stanworth,Tobias Tritschler,Wilma Bentum-Puijk,Frank Veerdonk,Sean Diepen,Gloria Vázquez‐Grande,Anne Turner,Bryan Wells,Lana Wahid,Derek Angus,Colin McArthur,Steven Webb,Michael Farkouh,Judith Hochman
+136 authors
,Ryan Zarychanski
Published
Aug 4, 2021
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Abstract

BackgroundThrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19.MethodsIn this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care–level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis. The primary outcome was organ support–free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of −1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline d-dimer level.Download a PDF of the Research Summary.ResultsThe trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met. Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support–free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58). The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2). The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high d-dimer cohort, 92.9% in the low d-dimer cohort, and 97.3% in the unknown d-dimer cohort. Major bleeding occurred in 1.9% of the patients receiving therapeutic-dose anticoagulation and in 0.9% of those receiving thromboprophylaxis.ConclusionsIn noncritically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support as compared with usual-care thromboprophylaxis. (ATTACC, ACTIV-4a, and REMAP-CAP ClinicalTrials.gov numbers, NCT04372589, NCT04505774, NCT04359277, and NCT02735707.) Quick Take Therapeutic Anticoagulation in Hospitalized Patients with Covid-19 2m 51s

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