Anticoagulation Strategies in Non–Critically Ill Patients with Covid-19

Zoe K. McQuilten; Balasubramanian Venkatesh; Vivekanand Jha; Jason Roberts; Susan C. Morpeth; James A. Totterdell; Grace M. McPhee; John Abraham; Niraj Bam; Methma Bandara; Ashpak K. Bangi; Lauren A. Barina; Bhupendra K. Basnet; Hasan Bhally; Khema R. Bhusal; Umesh Bogati; Asha C. Bowen; Andrew J. Burke; Devasahayam J. Christopher; Sanjeev D. Chunilal; Belinda Cochrane; Jennifer L. Curnow; Santa Kumar Das; Ashesh Dhungana; Gian Luca Di Tanna; Ravindra Dotel; Hyjel DSouza; Jack Dummer; Sourabh Dutta; Hong Foo; Timothy L. Gilbey; Michelle L. Giles; Kasiram Goli; Adrienne Gordon; Pradip Gyanwali; Dipak Haksar; Bernard J. Hudson; Manoj K. Jani; Purnima R. Jevaji; Sachin Jhawar; Aikaj Jindal; M. Joseph John; Mary John; Flavita B. John; Oommen John; Mark Jones; Rajesh D. Joshi; Prashanthi Kamath; Gagandeep Kang; Achyut R. Karki; Abhishek M. Karmalkar; Baldeep Kaur; Kalyan Chakravarthy Koganti; Jency Koshy; Mathew S.  Krishnamurthy; Jillian S. Lau; Sharon R. Lewin; Lyn-li Lim; Ian C. Marschner; Julie A. Marsh; Michael J. Maze; James M. McGree; James H. McMahon; Robert L. Medcalf; Eileen G. Merriman; Amol P. Misal; Jocelyn M. Mora; Vijaybabu K. Mudaliar; Vi Nguyen; Matthew V. O’Sullivan; Suman Pant; Pankaj Pant; David L. Paterson; David J. Price; Megan A. Rees; James O. Robinson; Benjamin A. Rogers; Sandhya Samuel; Joe Sasadeusz; Deepak Sharma; Prabhat K. Sharma; Roshan Shrestha; Sailesh K. Shrestha; Prajowl Shrestha; Urvi Shukla; Omar Shum; Christine Sommerville; Tim Spelman; Richard P.  Sullivan; Umashankar Thatavarthi; Huyen A. Tran; Nanette Trask; Clare L. Whitehead; Robert K. Mahar; Naomi E. Hammond; James D. McFadyen; Thomas L. Snelling; Joshua S. Davis; Justin T. Denholm; Steven Y.C. Tong

doi:10.1056/evidoa2200293

Anticoagulation Strategies in Non–Critically Ill Patients with Covid-19

Zoe K. McQuilten, Balasubramanian Venkatesh, Vivekanand Jha, Jason Roberts, Susan C. Morpeth, James A. Totterdell, Grace M. McPhee, John Abraham, Niraj Bam, Methma Bandara, Ashpak K. Bangi, Lauren A. Barina, Bhupendra K. Basnet, Hasan Bhally, Khema R. Bhusal, Umesh Bogati, Asha C. Bowen, Andrew J. Burke, Devasahayam J. Christopher, Sanjeev D. ChunilalBelinda Cochrane, Jennifer L. Curnow, Santa Kumar Das, Ashesh Dhungana, Gian Luca Di Tanna, Ravindra Dotel, Hyjel DSouza, Jack Dummer, Sourabh Dutta, Hong Foo, Timothy L. Gilbey, Michelle L. Giles, Kasiram Goli, Adrienne Gordon, Pradip Gyanwali, Dipak Haksar, Bernard J. Hudson, Manoj K. Jani, Purnima R. Jevaji, Sachin Jhawar, Aikaj Jindal, M. Joseph John, Mary John, Flavita B. John, Oommen John, Mark Jones, Rajesh D. Joshi, Prashanthi Kamath, Gagandeep Kang, Achyut R. Karki, Abhishek M. Karmalkar, Baldeep Kaur, Kalyan Chakravarthy Koganti, Jency Koshy, Mathew S. Krishnamurthy, Jillian S. Lau, Sharon R. Lewin, Lyn-li Lim, Ian C. Marschner, Julie A. Marsh, Michael J. Maze, James M. McGree, James H. McMahon, Robert L. Medcalf, Eileen G. Merriman, Amol P. Misal, Jocelyn M. Mora, Vijaybabu K. Mudaliar, Vi Nguyen, Matthew V. O’Sullivan, Suman Pant, Pankaj Pant, David L. Paterson, David J. Price, Megan A. Rees, James O. Robinson, Benjamin A. Rogers, Sandhya Samuel, Joe Sasadeusz, Deepak Sharma, Prabhat K. Sharma, Roshan Shrestha, Sailesh K. Shrestha, Prajowl Shrestha, Urvi Shukla, Omar Shum, Christine Sommerville, Tim Spelman, Richard P. Sullivan, Umashankar Thatavarthi, Huyen A. Tran, Nanette Trask, Clare L. Whitehead, Robert K. Mahar, Naomi E. Hammond, James D. McFadyen, Thomas L. Snelling, Joshua S. Davis, Justin T. Denholm, Steven Y.C. Tong

Research output: Contribution to journal › Article › peer-review

18 Citations (Scopus)

Abstract

BACKGROUND Optimal thromboprophylaxis for hospitalized patients with coronavirus disease 2019 (Covid-19) is uncertain. METHODS In an open-label, adaptive platform trial, we randomly assigned hospitalized adults with Covid-19 to low-dose low-molecular-weight heparin thromboprophylaxis or intermediate-dose or low-dose plus aspirin. In response to external evidence, the aspirin intervention was discontinued and a therapeutic-dose arm added. The primary end point was death or the requirement for new organ support by day 28, analyzed with a Bayesian logistic model. Enrolment was closed as a result of operational constraints. RESULTS Between February 2021 and March 2022, 1574 patients were randomly assigned. Among 1526 participants included in the analysis (India, n51273; Australia and New Zealand, n5138; and Nepal, n5115), the primary outcome occurred in 35 (5.9%) of 596 in low-dose, 25 (4.2%) of 601 in intermediate-dose, 20 (7.2%) of 279 in low-dose plus aspirin, and 7 (14%) of 50 in therapeutic-dose anticoagulation. Compared with low-dose thromboprophylaxis, the median adjusted odds ratio for the primary outcome for intermediate-dose was 0.74 (95% credible interval [CrI], 0.43 to 1.27; posterior probability of effectiveness [adjusted odds ratio,1; Pr], 86%), for low-dose plus aspirin 0.88 (95% CrI, 0.47 to 1.64; Pr, 65%), and for therapeutic-dose anticoagulation 2.22 (95% CrI, 0.77 to 6.20; Pr, 7%). Overall thrombotic and bleeding rates were 0.8% and 0.4%, respectively. There were 10 serious adverse reactions related to anticoagulation strategy, of which nine were grade 1 or 2 across study interventions and one grade 4 episode of retroperitoneal hematoma in a patient receiving intermediate-dose anticoagulation. CONCLUSIONS In hospitalized non–critically ill adults with Covid-19, compared with low-dose, there was an 86% posterior probability that intermediate-dose, 65% posterior probability that low-dose plus aspirin, and a 7% posterior probability that therapeutic-dose anticoagulation reduced the odds of death or requirement for organ support. No treatment strategy met prespecified stopping criteria before trial closure, precluding definitive conclusions.

Original language	English
Number of pages	14
Journal	NEJM Evidence
Volume	2
Issue number	2
Early online date	10 Dec 2022
DOIs	https://doi.org/10.1056/evidoa2200293
Publication status	Published - Feb 2023
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2023 Massachusetts Medical Society. All rights reserved.

Funding

ASCOT is supported by the Australian Partnership for Preparedness Research on Infectious Disease Emergencies (APPRISE), the BHP Foundation, Health Research Council of New Zealand, Hospital Research Foundation, the Macquarie Group Foundation, the Minderoo Foundation, the Pratt Foundation, Royal Brisbane and Women\u2019s Hospital Foundation, the Common Good (the Prince Charles Hospital Foundation), Wesley Medical Research, Chong Kun Dang Pharmaceutical Corporation, NSW Office for Health and Medical Research, Medical Research Future Fund (MRF2002132), and the Russell and Womersley Foundation. Drs. Venkatesh, McQuilten, Snelling, Hammond, Bowen, McFadyen, Lewin, Denholm, and Roberts are supported by Australian National Health and Medical Research Council or Medical Research Future Fund Investigator and Practitioner Grants. Dr. Jones\u2019s and Mr. Totterdell\u2019s work on this manuscript has been supported in-kind by the Snow Medical Foundation. The funding bodies had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Funders	Funder number
Australian Partnership for Preparedness Research on Infectious Disease Emergencies
BHP Foundation
Health Research Council of New Zealand
Hospital Research Foundation
Macquarie Group Foundation
Minderoo Foundation
Pratt Foundation
Royal Brisbane and Women’s Hospital Foundation
The Common Good
Wesley Medical Research
Chong Kun Dang Pharmaceutical
NSW Health and Medical Research
Australian Government	MRF2002132
Russell and Womersley Foundation
National Health and Medical Research Council
Snow Medical Foundation

Keywords

Anticoagulation/Thromboembolism (Pulmonary/Critical Care)
Coagulation
Viral Infections

ASJC Scopus subject areas

Drug Discovery
Pharmacology
Medicine (miscellaneous)

Access to Document

10.1056/evidoa2200293

Cite this

McQuilten, Z. K., Venkatesh, B., Jha, V., Roberts, J., Morpeth, S. C., Totterdell, J. A., McPhee, G. M., Abraham, J., Bam, N., Bandara, M., Bangi, A. K., Barina, L. A., Basnet, B. K., Bhally, H., Bhusal, K. R., Bogati, U., Bowen, A. C., Burke, A. J., Christopher, D. J., ... Tong, S. Y. C. (2023). Anticoagulation Strategies in Non–Critically Ill Patients with Covid-19. NEJM Evidence, 2(2). https://doi.org/10.1056/evidoa2200293

McQuilten, ZK, Venkatesh, B, Jha, V, Roberts, J, Morpeth, SC, Totterdell, JA, McPhee, GM, Abraham, J, Bam, N, Bandara, M, Bangi, AK, Barina, LA, Basnet, BK, Bhally, H, Bhusal, KR, Bogati, U, Bowen, AC, Burke, AJ, Christopher, DJ, Chunilal, SD, Cochrane, B, Curnow, JL, Das, SK, Dhungana, A, Tanna, GLD, Dotel, R, DSouza, H, Dummer, J, Dutta, S, Foo, H, Gilbey, TL, Giles, ML, Goli, K, Gordon, A, Gyanwali, P, Haksar, D, Hudson, BJ, Jani, MK, Jevaji, PR, Jhawar, S, Jindal, A, John, MJ, John, M, John, FB, John, O, Jones, M, Joshi, RD, Kamath, P, Kang, G, Karki, AR, Karmalkar, AM, Kaur, B, Koganti, KC, Koshy, J, Krishnamurthy, MS, Lau, JS, Lewin, SR, Lim, L, Marschner, IC, Marsh, JA, Maze, MJ, McGree, JM, McMahon, JH, Medcalf, RL, Merriman, EG, Misal, AP, Mora, JM, Mudaliar, VK, Nguyen, V, O’Sullivan, MV, Pant, S, Pant, P, Paterson, DL, Price, DJ, Rees, MA, Robinson, JO, Rogers, BA, Samuel, S, Sasadeusz, J, Sharma, D, Sharma, PK, Shrestha, R, Shrestha, SK, Shrestha, P, Shukla, U, Shum, O, Sommerville, C, Spelman, T, Sullivan, RP, Thatavarthi, U, Tran, HA, Trask, N, Whitehead, CL, Mahar, RK, Hammond, NE, McFadyen, JD, Snelling, TL, Davis, JS, Denholm, JT & Tong, SYC 2023, 'Anticoagulation Strategies in Non–Critically Ill Patients with Covid-19', NEJM Evidence, vol. 2, no. 2. https://doi.org/10.1056/evidoa2200293

@article{bce55fb5bb24469aba4be3e6308e7b67,

title = "Anticoagulation Strategies in Non–Critically Ill Patients with Covid-19",

abstract = "BACKGROUND Optimal thromboprophylaxis for hospitalized patients with coronavirus disease 2019 (Covid-19) is uncertain. METHODS In an open-label, adaptive platform trial, we randomly assigned hospitalized adults with Covid-19 to low-dose low-molecular-weight heparin thromboprophylaxis or intermediate-dose or low-dose plus aspirin. In response to external evidence, the aspirin intervention was discontinued and a therapeutic-dose arm added. The primary end point was death or the requirement for new organ support by day 28, analyzed with a Bayesian logistic model. Enrolment was closed as a result of operational constraints. RESULTS Between February 2021 and March 2022, 1574 patients were randomly assigned. Among 1526 participants included in the analysis (India, n51273; Australia and New Zealand, n5138; and Nepal, n5115), the primary outcome occurred in 35 (5.9\%) of 596 in low-dose, 25 (4.2\%) of 601 in intermediate-dose, 20 (7.2\%) of 279 in low-dose plus aspirin, and 7 (14\%) of 50 in therapeutic-dose anticoagulation. Compared with low-dose thromboprophylaxis, the median adjusted odds ratio for the primary outcome for intermediate-dose was 0.74 (95\% credible interval [CrI], 0.43 to 1.27; posterior probability of effectiveness [adjusted odds ratio,1; Pr], 86\%), for low-dose plus aspirin 0.88 (95\% CrI, 0.47 to 1.64; Pr, 65\%), and for therapeutic-dose anticoagulation 2.22 (95\% CrI, 0.77 to 6.20; Pr, 7\%). Overall thrombotic and bleeding rates were 0.8\% and 0.4\%, respectively. There were 10 serious adverse reactions related to anticoagulation strategy, of which nine were grade 1 or 2 across study interventions and one grade 4 episode of retroperitoneal hematoma in a patient receiving intermediate-dose anticoagulation. CONCLUSIONS In hospitalized non–critically ill adults with Covid-19, compared with low-dose, there was an 86\% posterior probability that intermediate-dose, 65\% posterior probability that low-dose plus aspirin, and a 7\% posterior probability that therapeutic-dose anticoagulation reduced the odds of death or requirement for organ support. No treatment strategy met prespecified stopping criteria before trial closure, precluding definitive conclusions.",

keywords = "Anticoagulation/Thromboembolism (Pulmonary/Critical Care), Coagulation, Viral Infections",

author = "McQuilten, \{Zoe K.\} and Balasubramanian Venkatesh and Vivekanand Jha and Jason Roberts and Morpeth, \{Susan C.\} and Totterdell, \{James A.\} and McPhee, \{Grace M.\} and John Abraham and Niraj Bam and Methma Bandara and Bangi, \{Ashpak K.\} and Barina, \{Lauren A.\} and Basnet, \{Bhupendra K.\} and Hasan Bhally and Bhusal, \{Khema R.\} and Umesh Bogati and Bowen, \{Asha C.\} and Burke, \{Andrew J.\} and Christopher, \{Devasahayam J.\} and Chunilal, \{Sanjeev D.\} and Belinda Cochrane and Curnow, \{Jennifer L.\} and Das, \{Santa Kumar\} and Ashesh Dhungana and Tanna, \{Gian Luca Di\} and Ravindra Dotel and Hyjel DSouza and Jack Dummer and Sourabh Dutta and Hong Foo and Gilbey, \{Timothy L.\} and Giles, \{Michelle L.\} and Kasiram Goli and Adrienne Gordon and Pradip Gyanwali and Dipak Haksar and Hudson, \{Bernard J.\} and Jani, \{Manoj K.\} and Jevaji, \{Purnima R.\} and Sachin Jhawar and Aikaj Jindal and John, \{M. Joseph\} and Mary John and John, \{Flavita B.\} and Oommen John and Mark Jones and Joshi, \{Rajesh D.\} and Prashanthi Kamath and Gagandeep Kang and Karki, \{Achyut R.\} and Karmalkar, \{Abhishek M.\} and Baldeep Kaur and Koganti, \{Kalyan Chakravarthy\} and Jency Koshy and Krishnamurthy, \{Mathew S.\} and Lau, \{Jillian S.\} and Lewin, \{Sharon R.\} and Lyn-li Lim and Marschner, \{Ian C.\} and Marsh, \{Julie A.\} and Maze, \{Michael J.\} and McGree, \{James M.\} and McMahon, \{James H.\} and Medcalf, \{Robert L.\} and Merriman, \{Eileen G.\} and Misal, \{Amol P.\} and Mora, \{Jocelyn M.\} and Mudaliar, \{Vijaybabu K.\} and Vi Nguyen and O{\textquoteright}Sullivan, \{Matthew V.\} and Suman Pant and Pankaj Pant and Paterson, \{David L.\} and Price, \{David J.\} and Rees, \{Megan A.\} and Robinson, \{James O.\} and Rogers, \{Benjamin A.\} and Sandhya Samuel and Joe Sasadeusz and Deepak Sharma and Sharma, \{Prabhat K.\} and Roshan Shrestha and Shrestha, \{Sailesh K.\} and Prajowl Shrestha and Urvi Shukla and Omar Shum and Christine Sommerville and Tim Spelman and Sullivan, \{Richard P.\} and Umashankar Thatavarthi and Tran, \{Huyen A.\} and Nanette Trask and Whitehead, \{Clare L.\} and Mahar, \{Robert K.\} and Hammond, \{Naomi E.\} and McFadyen, \{James D.\} and Snelling, \{Thomas L.\} and Davis, \{Joshua S.\} and Denholm, \{Justin T.\} and Tong, \{Steven Y.C.\}",

year = "2023",

month = feb,

doi = "10.1056/evidoa2200293",

language = "English",

volume = "2",

journal = "NEJM Evidence",

issn = "2766-5526",

publisher = "Massachusetts Medical Society",

number = "2",

}

TY - JOUR

T1 - Anticoagulation Strategies in Non–Critically Ill Patients with Covid-19

AU - McQuilten, Zoe K.

AU - Venkatesh, Balasubramanian

AU - Jha, Vivekanand

AU - Roberts, Jason

AU - Morpeth, Susan C.

AU - Totterdell, James A.

AU - McPhee, Grace M.

AU - Abraham, John

AU - Bam, Niraj

AU - Bandara, Methma

AU - Bangi, Ashpak K.

AU - Barina, Lauren A.

AU - Basnet, Bhupendra K.

AU - Bhally, Hasan

AU - Bhusal, Khema R.

AU - Bogati, Umesh

AU - Bowen, Asha C.

AU - Burke, Andrew J.

AU - Christopher, Devasahayam J.

AU - Chunilal, Sanjeev D.

AU - Cochrane, Belinda

AU - Curnow, Jennifer L.

AU - Das, Santa Kumar

AU - Dhungana, Ashesh

AU - Tanna, Gian Luca Di

AU - Dotel, Ravindra

AU - DSouza, Hyjel

AU - Dummer, Jack

AU - Dutta, Sourabh

AU - Foo, Hong

AU - Gilbey, Timothy L.

AU - Giles, Michelle L.

AU - Goli, Kasiram

AU - Gordon, Adrienne

AU - Gyanwali, Pradip

AU - Haksar, Dipak

AU - Hudson, Bernard J.

AU - Jani, Manoj K.

AU - Jevaji, Purnima R.

AU - Jhawar, Sachin

AU - Jindal, Aikaj

AU - John, M. Joseph

AU - John, Mary

AU - John, Flavita B.

AU - John, Oommen

AU - Jones, Mark

AU - Joshi, Rajesh D.

AU - Kamath, Prashanthi

AU - Kang, Gagandeep

AU - Karki, Achyut R.

AU - Karmalkar, Abhishek M.

AU - Kaur, Baldeep

AU - Koganti, Kalyan Chakravarthy

AU - Koshy, Jency

AU - Krishnamurthy, Mathew S.

AU - Lau, Jillian S.

AU - Lewin, Sharon R.

AU - Lim, Lyn-li

AU - Marschner, Ian C.

AU - Marsh, Julie A.

AU - Maze, Michael J.

AU - McGree, James M.

AU - McMahon, James H.

AU - Medcalf, Robert L.

AU - Merriman, Eileen G.

AU - Misal, Amol P.

AU - Mora, Jocelyn M.

AU - Mudaliar, Vijaybabu K.

AU - Nguyen, Vi

AU - O’Sullivan, Matthew V.

AU - Pant, Suman

AU - Pant, Pankaj

AU - Paterson, David L.

AU - Price, David J.

AU - Rees, Megan A.

AU - Robinson, James O.

AU - Rogers, Benjamin A.

AU - Samuel, Sandhya

AU - Sasadeusz, Joe

AU - Sharma, Deepak

AU - Sharma, Prabhat K.

AU - Shrestha, Roshan

AU - Shrestha, Sailesh K.

AU - Shrestha, Prajowl

AU - Shukla, Urvi

AU - Shum, Omar

AU - Sommerville, Christine

AU - Spelman, Tim

AU - Sullivan, Richard P.

AU - Thatavarthi, Umashankar

AU - Tran, Huyen A.

AU - Trask, Nanette

AU - Whitehead, Clare L.

AU - Mahar, Robert K.

AU - Hammond, Naomi E.

AU - McFadyen, James D.

AU - Snelling, Thomas L.

AU - Davis, Joshua S.

AU - Denholm, Justin T.

AU - Tong, Steven Y.C.

PY - 2023/2

Y1 - 2023/2

N2 - BACKGROUND Optimal thromboprophylaxis for hospitalized patients with coronavirus disease 2019 (Covid-19) is uncertain. METHODS In an open-label, adaptive platform trial, we randomly assigned hospitalized adults with Covid-19 to low-dose low-molecular-weight heparin thromboprophylaxis or intermediate-dose or low-dose plus aspirin. In response to external evidence, the aspirin intervention was discontinued and a therapeutic-dose arm added. The primary end point was death or the requirement for new organ support by day 28, analyzed with a Bayesian logistic model. Enrolment was closed as a result of operational constraints. RESULTS Between February 2021 and March 2022, 1574 patients were randomly assigned. Among 1526 participants included in the analysis (India, n51273; Australia and New Zealand, n5138; and Nepal, n5115), the primary outcome occurred in 35 (5.9%) of 596 in low-dose, 25 (4.2%) of 601 in intermediate-dose, 20 (7.2%) of 279 in low-dose plus aspirin, and 7 (14%) of 50 in therapeutic-dose anticoagulation. Compared with low-dose thromboprophylaxis, the median adjusted odds ratio for the primary outcome for intermediate-dose was 0.74 (95% credible interval [CrI], 0.43 to 1.27; posterior probability of effectiveness [adjusted odds ratio,1; Pr], 86%), for low-dose plus aspirin 0.88 (95% CrI, 0.47 to 1.64; Pr, 65%), and for therapeutic-dose anticoagulation 2.22 (95% CrI, 0.77 to 6.20; Pr, 7%). Overall thrombotic and bleeding rates were 0.8% and 0.4%, respectively. There were 10 serious adverse reactions related to anticoagulation strategy, of which nine were grade 1 or 2 across study interventions and one grade 4 episode of retroperitoneal hematoma in a patient receiving intermediate-dose anticoagulation. CONCLUSIONS In hospitalized non–critically ill adults with Covid-19, compared with low-dose, there was an 86% posterior probability that intermediate-dose, 65% posterior probability that low-dose plus aspirin, and a 7% posterior probability that therapeutic-dose anticoagulation reduced the odds of death or requirement for organ support. No treatment strategy met prespecified stopping criteria before trial closure, precluding definitive conclusions.

AB - BACKGROUND Optimal thromboprophylaxis for hospitalized patients with coronavirus disease 2019 (Covid-19) is uncertain. METHODS In an open-label, adaptive platform trial, we randomly assigned hospitalized adults with Covid-19 to low-dose low-molecular-weight heparin thromboprophylaxis or intermediate-dose or low-dose plus aspirin. In response to external evidence, the aspirin intervention was discontinued and a therapeutic-dose arm added. The primary end point was death or the requirement for new organ support by day 28, analyzed with a Bayesian logistic model. Enrolment was closed as a result of operational constraints. RESULTS Between February 2021 and March 2022, 1574 patients were randomly assigned. Among 1526 participants included in the analysis (India, n51273; Australia and New Zealand, n5138; and Nepal, n5115), the primary outcome occurred in 35 (5.9%) of 596 in low-dose, 25 (4.2%) of 601 in intermediate-dose, 20 (7.2%) of 279 in low-dose plus aspirin, and 7 (14%) of 50 in therapeutic-dose anticoagulation. Compared with low-dose thromboprophylaxis, the median adjusted odds ratio for the primary outcome for intermediate-dose was 0.74 (95% credible interval [CrI], 0.43 to 1.27; posterior probability of effectiveness [adjusted odds ratio,1; Pr], 86%), for low-dose plus aspirin 0.88 (95% CrI, 0.47 to 1.64; Pr, 65%), and for therapeutic-dose anticoagulation 2.22 (95% CrI, 0.77 to 6.20; Pr, 7%). Overall thrombotic and bleeding rates were 0.8% and 0.4%, respectively. There were 10 serious adverse reactions related to anticoagulation strategy, of which nine were grade 1 or 2 across study interventions and one grade 4 episode of retroperitoneal hematoma in a patient receiving intermediate-dose anticoagulation. CONCLUSIONS In hospitalized non–critically ill adults with Covid-19, compared with low-dose, there was an 86% posterior probability that intermediate-dose, 65% posterior probability that low-dose plus aspirin, and a 7% posterior probability that therapeutic-dose anticoagulation reduced the odds of death or requirement for organ support. No treatment strategy met prespecified stopping criteria before trial closure, precluding definitive conclusions.

KW - Anticoagulation/Thromboembolism (Pulmonary/Critical Care)

KW - Coagulation

KW - Viral Infections

UR - http://dx.doi.org/10.1056/evidoa2200293

UR - https://www.scopus.com/pages/publications/85153874003

U2 - 10.1056/evidoa2200293

DO - 10.1056/evidoa2200293

M3 - Article

SN - 2766-5526

VL - 2

JO - NEJM Evidence

JF - NEJM Evidence

IS - 2

ER -

Anticoagulation Strategies in Non–Critically Ill Patients with Covid-19

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