Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19
Goligher, Ewan C; Bradbury, Charlotte A; McVerry, Bryan J; Lawler, Patrick R; Berger, Jeffrey S; Gong, Michelle N; Carrier, Marc; Reynolds, Harmony R; Kumar, Anand; Turgeon, Alexis F; Kornblith, Lucy Z; Kahn, Susan R; Marshall, John C; Kim, Keri S; Houston, Brett L; Derde, Lennie P G; Cushman, Mary; Tritschler, Tobias; Angus, Derek C; Godoy, Lucas C; McQuilten, Zoe; Kirwan, Bridget-Anne; Farkouh, Michael E; Brooks, Maria M; Lewis, Roger J; Berry, Lindsay R; Lorenzi, Elizabeth; Gordon, Anthony C; Ahuja, Tania; Al-Beidh, Farah; Annane, Djillali; Arabi, Yaseen M; Aryal, Diptesh; Baumann Kreuziger, Lisa; Beane, Abi; Bhimani, Zahra; Bihari, Shailesh; Billett, Henny H; Bond, Lindsay; Bonten, Marc; Brunkhorst, Frank; Buxton, Meredith; Buzgau, Adrian; Castellucci, Lana A; Chekuri, Sweta; Chen, Jen-Ting; Cheng, Allen C; Chkhikvadze, Tamta; Coiffard, Benjamin; Contreras, Aira; Costantini, Todd W; de Brouwer, Sophie; Detry, Michelle A; Duggal, Abhijit; DžavÃk, VladimÃr; Effron, Mark B; Eng, Heather F; Escobedo, Jorge; Estcourt, Lise J; Everett, Brendan M; Fergusson, Dean A; Fitzgerald, Mark; Fowler, Robert A; Froess, Joshua D; Fu, Zhuxuan; Galanaud, Jean P; Galen, Benjamin T; Gandotra, Sheetal; Girard, Timothy D; Goodman, Andrew L; Goossens, Herman; Green, Cameron; Greenstein, Yonatan Y; Gross, Peter L; Haniffa, Rashan; Hegde, Sheila M; Hendrickson, Carolyn M; Higgins, Alisa M; Hindenburg, Alexander A; Hope, Aluko A; Horowitz, James M; Horvat, Christopher M; Huang, David T; Hudock, Kristin; Hunt, Beverley J; Husain, Mansoor; Hyzy, Robert C; Jacobson, Jeffrey R; Jayakumar, Devachandran; Keller, Norma M; Khan, Akram; Kim, Yuri; Kindzelski, Andrei; King, Andrew J; Knudson, M Margaret; Kornblith, Aaron E; Kutcher, Matthew E; Laffan, Michael A; Lamontagne, Francois; Le Gal, Grégoire; Leeper, Christine M; Leifer, Eric S; Lim, George; Gallego Lima, Felipe; Linstrum, Kelsey; Litton, Edward; Lopez-Sendon, Jose; Lother, Sylvain A; Marten, Nicole; Saud Marinez, Andréa; Martinez, Mary; Mateos Garcia, Eduardo; Mavromichalis, Stavroula; McAuley, Daniel F; McDonald, Emily G; McGlothlin, Anna; McGuinness, Shay P; Middeldorp, Saskia; Montgomery, Stephanie K; Mouncey, Paul R; Murthy, Srinivas; Nair, Girish B; Nair, Rahul; Nichol, Alistair D; Nicolau, Jose C; Nunez-Garcia, Brenda; Park, John J; Park, Pauline K; Parke, Rachael L; Parker, Jane C; Parnia, Sam; Paul, Jonathan D; Pompilio, Mauricio; Quigley, John G; Rosenson, Robert S; Rost, Natalia S; Rowan, Kathryn; Santos, Fernanda O; Santos, Marlene; Santos, Mayler O; Satterwhite, Lewis; Saunders, Christina T; Schreiber, Jake; Schutgens, Roger E G; Seymour, Christopher W; Siegal, Deborah M; Silva, Delcio G; Singhal, Aneesh B; Slutsky, Arthur S; Solvason, Dayna; Stanworth, Simon J; Turner, Anne M; van Bentum-Puijk, Wilma; van de Veerdonk, Frank L; van Diepen, Sean; Vazquez-Grande, Gloria; Wahid, Lana; Wareham, Vanessa; Widmer, R Jay; Wilson, Jennifer G; Yuriditsky, Eugene; Zhong, Yongqi; Berry, Scott M; McArthur, Colin J; Neal, Matthew D; Hochman, Judith S; Webb, Steven A; Zarychanski, Ryan
BACKGROUND:Thrombosis and inflammation may contribute to morbidity and mortality among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill patients with Covid-19. METHODS:In an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care. 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. RESULTS:The trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation. Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis). The median value for organ support-free days was 1 (interquartile range, -1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, -1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio <1.2], 99.9%). The percentage of patients who survived to hospital discharge was similar in the two groups (62.7% and 64.5%, respectively; adjusted odds ratio, 0.84; 95% credible interval, 0.64 to 1.11). Major bleeding occurred in 3.8% of the patients assigned to therapeutic-dose anticoagulation and in 2.3% of those assigned to usual-care pharmacologic thromboprophylaxis. CONCLUSIONS:In critically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin did not result in a greater probability of survival to hospital discharge or a greater number of days free of cardiovascular or respiratory organ support than did usual-care pharmacologic thromboprophylaxis. (REMAP-CAP, ACTIV-4a, and ATTACC ClinicalTrials.gov numbers, NCT02735707, NCT04505774, NCT04359277, and NCT04372589.).
PMCID:8362592
PMID: 34351722
ISSN: 1533-4406
CID: 4980752