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

ATTACC Investigators; ACTIV-4a Investigators; REMAP-CAP Investigators; Lawler, Patrick R; Goligher, Ewan C; Berger, Jeffrey S; Neal, Matthew D; McVerry, Bryan J; Nicolau, Jose C; Gong, Michelle N; Carrier, Marc; Rosenson, Robert S; Reynolds, Harmony R; Turgeon, Alexis F; Escobedo, Jorge; Huang, David T; Bradbury, Charlotte A; Houston, Brett L; Kornblith, Lucy Z; Kumar, Anand; Kahn, Susan R; Cushman, Mary; McQuilten, Zoe; Slutsky, Arthur S; Kim, Keri S; Gordon, Anthony C; Kirwan, Bridget-Anne; Brooks, Maria M; Higgins, Alisa M; Lewis, Roger J; Lorenzi, Elizabeth; Berry, Scott M; Berry, Lindsay R; Aday, Aaron W; 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; Costantini, Todd W; de Brouwer, Sophie; Derde, Lennie PG; Detry, Michelle A; Duggal, Abhijit; Džavík, Vladimír; Effron, Mark B; Estcourt, Lise J; Everett, Brendan M; Fergusson, Dean A; Fitzgerald, Mark; Fowler, Robert A; Galanaud, Jean P; Galen, Benjamin T; Gandotra, Sheetal; García-Madrona, Sebastian; Girard, Timothy D; Godoy, Lucas C; Goodman, Andrew L; Goossens, Herman; Green, Cameron; Greenstein, Yonatan Y; Gross, Peter L; Hamburg, Naomi M; Haniffa, Rashan; Hanna, George; Hanna, Nicholas; Hegde, Sheila M; Hendrickson, Carolyn M; Hite, R Duncan; Hindenburg, Alexander A; Hope, Aluko A; Horowitz, James M; Horvat, Christopher M; Hudock, Kristin; Hunt, Beverley J; Husain, Mansoor; Hyzy, Robert C; Iyer, Vivek N; Jacobson, Jeffrey R; Jayakumar, Devachandran; Keller, Norma M; Khan, Akram; Kim, Yuri; Kindzelski, Andrei L; King, Andrew J; Knudson, M Margaret; Kornblith, Aaron E; Krishnan, Vidya; Kutcher, Matthew E; Laffan, Michael A; Lamontagne, Francois; Le Gal, Grégoire; Leeper, Christine M; Leifer, Eric S; Lim, George; Lima, Felipe Gallego; Linstrum, Kelsey; Litton, Edward; Lopez-Sendon, Jose; Lopez-Sendon Moreno, Jose L; Lother, Sylvain A; Malhotra, Saurabh; Marcos, Miguel; Saud Marinez, Andréa; Marshall, John C; Marten, Nicole; Matthay, Michael A; McAuley, Daniel F; McDonald, Emily G; McGlothlin, Anna; McGuinness, Shay P; Middeldorp, Saskia; Montgomery, Stephanie K; Moore, Steven C; Morillo Guerrero, Raquel; Mouncey, Paul R; Murthy, Srinivas; Nair, Girish B; Nair, Rahul; Nichol, Alistair D; Nunez-Garcia, Brenda; Pandey, Ambarish; Park, Pauline K; Parke, Rachael L; Parker, Jane C; Parnia, Sam; Paul, Jonathan D; Pérez González, Yessica S; Pompilio, Mauricio; Prekker, Matthew E; Quigley, John G; Rost, Natalia S; Rowan, Kathryn; Santos, Fernanda O; Santos, Marlene; Olombrada Santos, Mayler; Satterwhite, Lewis; Saunders, Christina T; Schutgens, Roger EG; Seymour, Christopher W; Siegal, Deborah M; Silva, Delcio G; Shankar-Hari, Manu; Sheehan, John P; Singhal, Aneesh B; Solvason, Dayna; Stanworth, Simon J; Tritschler, Tobias; Turner, Anne M; van Bentum-Puijk, Wilma; van de Veerdonk, Frank L; van Diepen, Sean; Vazquez-Grande, Gloria; Wahid, Lana; Wareham, Vanessa; Wells, Bryan J; Widmer, R Jay; Wilson, Jennifer G; Yuriditsky, Eugene; Zampieri, Fernando G; Angus, Derek C; McArthur, Colin J; Webb, Steven A; Farkouh, Michael E; Hochman, Judith S; Zarychanski, Ryan

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

dc.contributor.author	ATTACC Investigators
dc.contributor.author	ACTIV-4a Investigators
dc.contributor.author	REMAP-CAP Investigators
dc.contributor.author	Lawler, Patrick R
dc.contributor.author	Goligher, Ewan C
dc.contributor.author	Berger, Jeffrey S
dc.contributor.author	Neal, Matthew D
dc.contributor.author	McVerry, Bryan J
dc.contributor.author	Nicolau, Jose C
dc.contributor.author	Gong, Michelle N
dc.contributor.author	Carrier, Marc
dc.contributor.author	Rosenson, Robert S
dc.contributor.author	Reynolds, Harmony R
dc.contributor.author	Turgeon, Alexis F
dc.contributor.author	Escobedo, Jorge
dc.contributor.author	Huang, David T
dc.contributor.author	Bradbury, Charlotte A
dc.contributor.author	Houston, Brett L
dc.contributor.author	Kornblith, Lucy Z
dc.contributor.author	Kumar, Anand
dc.contributor.author	Kahn, Susan R
dc.contributor.author	Cushman, Mary
dc.contributor.author	McQuilten, Zoe
dc.contributor.author	Slutsky, Arthur S
dc.contributor.author	Kim, Keri S
dc.contributor.author	Gordon, Anthony C
dc.contributor.author	Kirwan, Bridget-Anne
dc.contributor.author	Brooks, Maria M
dc.contributor.author	Higgins, Alisa M
dc.contributor.author	Lewis, Roger J
dc.contributor.author	Lorenzi, Elizabeth
dc.contributor.author	Berry, Scott M
dc.contributor.author	Berry, Lindsay R
dc.contributor.author	Aday, Aaron W
dc.contributor.author	Al-Beidh, Farah
dc.contributor.author	Annane, Djillali
dc.contributor.author	Arabi, Yaseen M
dc.contributor.author	Aryal, Diptesh
dc.contributor.author	Baumann Kreuziger, Lisa
dc.contributor.author	Beane, Abi
dc.contributor.author	Bhimani, Zahra
dc.contributor.author	Bihari, Shailesh
dc.contributor.author	Billett, Henny H
dc.contributor.author	Bond, Lindsay
dc.contributor.author	Bonten, Marc
dc.contributor.author	Brunkhorst, Frank
dc.contributor.author	Buxton, Meredith
dc.contributor.author	Buzgau, Adrian
dc.contributor.author	Castellucci, Lana A
dc.contributor.author	Chekuri, Sweta
dc.contributor.author	Chen, Jen-Ting
dc.contributor.author	Cheng, Allen C
dc.contributor.author	Chkhikvadze, Tamta
dc.contributor.author	Coiffard, Benjamin
dc.contributor.author	Costantini, Todd W
dc.contributor.author	de Brouwer, Sophie
dc.contributor.author	Derde, Lennie PG
dc.contributor.author	Detry, Michelle A
dc.contributor.author	Duggal, Abhijit
dc.contributor.author	Džavík, Vladimír
dc.contributor.author	Effron, Mark B
dc.contributor.author	Estcourt, Lise J
dc.contributor.author	Everett, Brendan M
dc.contributor.author	Fergusson, Dean A
dc.contributor.author	Fitzgerald, Mark
dc.contributor.author	Fowler, Robert A
dc.contributor.author	Galanaud, Jean P
dc.contributor.author	Galen, Benjamin T
dc.contributor.author	Gandotra, Sheetal
dc.contributor.author	García-Madrona, Sebastian
dc.contributor.author	Girard, Timothy D
dc.contributor.author	Godoy, Lucas C
dc.contributor.author	Goodman, Andrew L
dc.contributor.author	Goossens, Herman
dc.contributor.author	Green, Cameron
dc.contributor.author	Greenstein, Yonatan Y
dc.contributor.author	Gross, Peter L
dc.contributor.author	Hamburg, Naomi M
dc.contributor.author	Haniffa, Rashan
dc.contributor.author	Hanna, George
dc.contributor.author	Hanna, Nicholas
dc.contributor.author	Hegde, Sheila M
dc.contributor.author	Hendrickson, Carolyn M
dc.contributor.author	Hite, R Duncan
dc.contributor.author	Hindenburg, Alexander A
dc.contributor.author	Hope, Aluko A
dc.contributor.author	Horowitz, James M
dc.contributor.author	Horvat, Christopher M
dc.contributor.author	Hudock, Kristin
dc.contributor.author	Hunt, Beverley J
dc.contributor.author	Husain, Mansoor
dc.contributor.author	Hyzy, Robert C
dc.contributor.author	Iyer, Vivek N
dc.contributor.author	Jacobson, Jeffrey R
dc.contributor.author	Jayakumar, Devachandran
dc.contributor.author	Keller, Norma M
dc.contributor.author	Khan, Akram
dc.contributor.author	Kim, Yuri
dc.contributor.author	Kindzelski, Andrei L
dc.contributor.author	King, Andrew J
dc.contributor.author	Knudson, M Margaret
dc.contributor.author	Kornblith, Aaron E
dc.contributor.author	Krishnan, Vidya
dc.contributor.author	Kutcher, Matthew E
dc.contributor.author	Laffan, Michael A
dc.contributor.author	Lamontagne, Francois
dc.contributor.author	Le Gal, Grégoire
dc.contributor.author	Leeper, Christine M
dc.contributor.author	Leifer, Eric S
dc.contributor.author	Lim, George
dc.contributor.author	Lima, Felipe Gallego
dc.contributor.author	Linstrum, Kelsey
dc.contributor.author	Litton, Edward
dc.contributor.author	Lopez-Sendon, Jose
dc.contributor.author	Lopez-Sendon Moreno, Jose L
dc.contributor.author	Lother, Sylvain A
dc.contributor.author	Malhotra, Saurabh
dc.contributor.author	Marcos, Miguel
dc.contributor.author	Saud Marinez, Andréa
dc.contributor.author	Marshall, John C
dc.contributor.author	Marten, Nicole
dc.contributor.author	Matthay, Michael A
dc.contributor.author	McAuley, Daniel F
dc.contributor.author	McDonald, Emily G
dc.contributor.author	McGlothlin, Anna
dc.contributor.author	McGuinness, Shay P
dc.contributor.author	Middeldorp, Saskia
dc.contributor.author	Montgomery, Stephanie K
dc.contributor.author	Moore, Steven C
dc.contributor.author	Morillo Guerrero, Raquel
dc.contributor.author	Mouncey, Paul R
dc.contributor.author	Murthy, Srinivas
dc.contributor.author	Nair, Girish B
dc.contributor.author	Nair, Rahul
dc.contributor.author	Nichol, Alistair D
dc.contributor.author	Nunez-Garcia, Brenda
dc.contributor.author	Pandey, Ambarish
dc.contributor.author	Park, Pauline K
dc.contributor.author	Parke, Rachael L
dc.contributor.author	Parker, Jane C
dc.contributor.author	Parnia, Sam
dc.contributor.author	Paul, Jonathan D
dc.contributor.author	Pérez González, Yessica S
dc.contributor.author	Pompilio, Mauricio
dc.contributor.author	Prekker, Matthew E
dc.contributor.author	Quigley, John G
dc.contributor.author	Rost, Natalia S
dc.contributor.author	Rowan, Kathryn
dc.contributor.author	Santos, Fernanda O
dc.contributor.author	Santos, Marlene
dc.contributor.author	Olombrada Santos, Mayler
dc.contributor.author	Satterwhite, Lewis
dc.contributor.author	Saunders, Christina T
dc.contributor.author	Schutgens, Roger EG
dc.contributor.author	Seymour, Christopher W
dc.contributor.author	Siegal, Deborah M
dc.contributor.author	Silva, Delcio G
dc.contributor.author	Shankar-Hari, Manu
dc.contributor.author	Sheehan, John P
dc.contributor.author	Singhal, Aneesh B
dc.contributor.author	Solvason, Dayna
dc.contributor.author	Stanworth, Simon J
dc.contributor.author	Tritschler, Tobias
dc.contributor.author	Turner, Anne M
dc.contributor.author	van Bentum-Puijk, Wilma
dc.contributor.author	van de Veerdonk, Frank L
dc.contributor.author	van Diepen, Sean
dc.contributor.author	Vazquez-Grande, Gloria
dc.contributor.author	Wahid, Lana
dc.contributor.author	Wareham, Vanessa
dc.contributor.author	Wells, Bryan J
dc.contributor.author	Widmer, R Jay
dc.contributor.author	Wilson, Jennifer G
dc.contributor.author	Yuriditsky, Eugene
dc.contributor.author	Zampieri, Fernando G
dc.contributor.author	Angus, Derek C
dc.contributor.author	McArthur, Colin J
dc.contributor.author	Webb, Steven A
dc.contributor.author	Farkouh, Michael E
dc.contributor.author	Hochman, Judith S
dc.contributor.author	Zarychanski, Ryan
dc.date.accessioned	2021-08-20T06:09:37Z
dc.date.available	2021-08-20T06:09:37Z
dc.date.issued	2021-08-04
dc.date.updated	2021-08-20T06:09:30Z
dc.description.abstract	Background 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. Methods 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. Results 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. Conclusions 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, NCT02735707, and NCT04359277.).
dc.identifier.issn	0028-4793
dc.identifier.issn	1533-4406
dc.identifier.uri	https://hdl.handle.net/10161/23607
dc.language	eng
dc.publisher	Massachusetts Medical Society
dc.relation.ispartof	The New England journal of medicine
dc.relation.isversionof	10.1056/nejmoa2105911
dc.subject	ATTACC Investigators
dc.subject	ACTIV-4a Investigators
dc.subject	REMAP-CAP Investigators
dc.title	Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19.
dc.type	Journal article
duke.contributor.orcid	Wahid, Lana\|0000-0002-2160-3287
pubs.organisational-group	School of Medicine
pubs.organisational-group	Medicine, General Internal Medicine
pubs.organisational-group	Duke
pubs.organisational-group	Medicine
pubs.organisational-group	Clinical Science Departments
pubs.publication-status	Published