Portal de Periódicos da CAPES

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

2021; Massachusetts Medical Society; Volume: 385; Issue: 9 Linguagem: Inglês

10.1056/nejmoa2105911

1533-4406

Patrick R. Lawler, Ewan C. Goligher, Jeffrey S. Berger, Matthew D. Neal, Bryan J. McVerry, José Carlos Nicolau, Michelle N. Gong, Marc Carrier, Robert S Rosenson, Harmony R. Reynolds, Alexis F. Turgeon, Jorge Escobedo, David T. Huang, Charlotte Bradbury, Brett L. Houston, Lucy Z. Kornblith, Anand Kumar, Susan R. Kahn, Mary Cushman, Zoe McQuilten, Arthur S. Slutsky, Keri S. Kim, Anthony Gordon, Bridget‐Anne Kirwan, Maria M. Brooks, Alisa M. Higgins, Roger Lewis, Elizabeth Lorenzi, Scott Berry, Lindsay R. Berry, Aaron W. Aday, Farah Al-Beidh, Djillali Annane, Yaseen M. Arabi, Diptesh Aryal, Lisa Baumann Kreuziger, Abi Beane, Zahra Bhimani, Shailesh Bihari, Henny H. Billett, Lindsay Bond, Marc J. M. Bonten, Frank Brunkhorst, Meredith Buxton, Adrian Buzgau, Lana A. Castellucci, Sweta Chekuri, Jen‐Ting Chen, Allen C. Cheng, Tamta Chkhikvadze, Benjamin Coiffard, Todd W. Costantini, Sophie de Brouwer, Lennie Derde, Michelle A. Detry, Abhijit Duggal, Vladimír Džavík, Mark B. Effron, Lise J Estcourt, Brendan M. Everett, Dean Fergusson, Mark Fitzgerald, Robert Fowler, J.‐P. Galanaud, Benjamin Galen, Sheetal Gandotra, Sebastián García‐Madrona, Timothy D. Girard, Lucas C. Godoy, Andrew L. Goodman, Herman Goossens, Cameron Green, Yonatan Greenstein, Peter L Gross, Naomi M. Hamburg, Rashan Haniffa, George P. Hanna, Nicholas Hanna, Sheila M. Hegde, Carolyn M. Hendrickson, R. Duncan Hite, Alexander Hindenburg, Aluko A. Hope, James M Horowitz, Christopher M. Horvat, Kristin Hudock, Beverley J. Hunt, Mansoor Husain, Robert C. Hyzy, Vivek N. Iyer, Jeffrey R. Jacobson, Devachandran Jayakumar, Norma Keller, Akram Khan, Yuri Kim, Andrei Kindzelski, Andrew J. King, M. Margaret Knudson, Aaron E. Kornblith, Vidya Krishnan, Matthew Kutcher, Michael Laffan, François Lamontagne, Grégoire Le Gal, Christine M. Leeper, Eric Leifer, George Lim, Felipe Gallego Lima, Kelsey Linstrum, Edward Litton, José Luis López-Sendón, José Luis López-Sendón, Sylvain Lother, Saurabh Malhotra, Miguel Marcos, Andréa Saud Marinez, John C. Marshall, Nicole Marten, Michael A. Matthay, Daniel F. McAuley, Emily G McDonald, Anna McGlothlin, Shay McGuinness, Saskia Middeldorp, Stephanie K. Montgomery, S.C. Moore, Raquel Morillo Guerrero, Paul Mouncey, Srinivas Murthy, Girish B. Nair, Rahul Nair, Alistair Nichol, Brenda Nunez‐Garcia, Ambarish Pandey, Pauline K. Park, Rachael Parke, Rachael Parke, Sam Parnia, Jonathan Paul, Yessica S Pérez González, Mauricio Pompilio, Matthew E Prekker, John G. Quigley, Natalia S Rost, Kathy Rowan, Fernanda O Santos, Marlene Santos, Mayler Olombrada Nunes de Santos, Lewis Satterwhite, Christina Saunders, Roger Schutgens, Christopher W. Seymour, Deborah Siegal, Delcio G Silva, Manu Shankar‐Hari, John P. Sheehan, Aneesh B. Singhal, Dayna Solvason, Simon Stanworth, Tobias Tritschler, Anne Turner, Wilma van Bentum-Puijk, Frank L. van de Veerdonk, Sean van Diepen, Gloria Vázquez‐Grande, Lana Wahid, Vanessa Wareham, Bryan Wells, R. Jay Widmer, Jennifer G. Wilson, Eugene Yuriditsky, Fernando G Zampieri, Derek C. Angus, Colin J McArthur, Steven A. Webb, Michael E. Farkouh, Judith S. Hochman, Ryan Zarychanski,

Long-Term Effects of COVID-19

Thrombosis 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.In 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.The 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.In 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.).