Heparin Dose Intensity and Organ Support-Free Days in Patients Hospitalized for COVID-19

Lucas C. Godoy; Matthew D. Neal; Ewan C. Goligher; Mary Cushman; Brett L. Houston; Charlotte A. Bradbury; Zoe K. McQuilten; Tobias Tritschler; Susan R. Kahn; Lindsay R. Berry; Elizabeth Lorenzi; Tom Jensen; Alisa M. Higgins; Lucy Z. Kornblith; Jeffrey S. Berger; Michelle N. Gong; Jonathan D. Paul; Lana A. Castellucci; Grégoire Le Gal; Sylvain A. Lother; Robert S. Rosenson; Lennie P.G. Derde; Anand Kumar; Bryan J. McVerry; Jose C. Nicolau; Eric Leifer; Jorge Escobedo; David T. Huang; Harmony R. Reynolds; Marc Carrier; Keri S. Kim; Beverley J. Hunt; Arthur S. Slutsky; Alexis F. Turgeon; Steven A. Webb; Colin J. McArthur; Michael E. Farkouh; Judith S. Hochman; Ryan Zarychanski; Patrick R. Lawler

doi:10.1016/j.jacadv.2023.100780

Heparin Dose Intensity and Organ Support-Free Days in Patients Hospitalized for COVID-19

Lucas C. Godoy, Matthew D. Neal, Ewan C. Goligher, Mary Cushman, Brett L. Houston, Charlotte A. Bradbury, Zoe K. McQuilten, Tobias Tritschler, Susan R. Kahn, Lindsay R. Berry, Elizabeth Lorenzi, Tom Jensen, Alisa M. Higgins, Lucy Z. Kornblith, Jeffrey S. Berger, Michelle N. Gong, Jonathan D. Paul, Lana A. Castellucci, Grégoire Le Gal, Sylvain A. LotherRobert S. Rosenson, Lennie P.G. Derde, Anand Kumar, Bryan J. McVerry, Jose C. Nicolau, Eric Leifer, Jorge Escobedo, David T. Huang, Harmony R. Reynolds, Marc Carrier, Keri S. Kim, Beverley J. Hunt, Arthur S. Slutsky, Alexis F. Turgeon, Steven A. Webb, Colin J. McArthur, Michael E. Farkouh, Judith S. Hochman, Ryan Zarychanski, Patrick R. Lawler

Medicine

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

2 Scopus citations

Abstract

Background: Clinical trials suggest that therapeutic-dose heparin may prevent critical illness and vascular complications due to COVID-19, but knowledge gaps exist regarding the efficacy of therapeutic heparin including its comparative effect relative to intermediate-dose anticoagulation. Objectives: The authors performed 2 complementary secondary analyses of a completed randomized clinical trial: 1) a prespecified per-protocol analysis; and 2) an exploratory dose-based analysis to compare the effect of therapeutic-dose heparin with low- and intermediate-dose heparin. Methods: Patients who received initial anticoagulation dosed consistently with randomization were included. The primary outcome was organ support-free days (OSFDs), a combination of in-hospital death and days free of organ support through day 21. Results: Among 2,860 participants, 1,761 (92.8%) noncritically ill and 857 (89.1%) critically ill patients were treated per-protocol. Among noncritically ill per-protocol patients, the posterior probability that therapeutic-dose heparin improved OSFDs as compared with usual care was 99.3% (median adjusted OR: 1.36; 95% credible interval [CrI]: 1.07-1.74). Therapeutic heparin had a high posterior probability of efficacy relative to both low- (94.6%; adjusted OR: 1.26; 95% CrI: 0.95-1.64) and intermediate- (99.8%; adjusted OR: 1.80; 95% CrI: 1.22-2.62) dose thromboprophylaxis. Among critically ill per-protocol patients, the posterior probability that therapeutic heparin improved outcomes was low. Conclusions: Among noncritically ill patients hospitalized for COVID-19 who were randomized to and initially received therapeutic-dose anticoagulation, heparin, compared with usual care, was associated with improved OSFDs, a combination of in-hospital death and days free of organ support. Therapeutic heparin appeared superior to both low- and intermediate-dose thromboprophylaxis.

Original language	English (US)
Article number	100780
Journal	JACC: Advances
Volume	3
Issue number	3
DOIs	https://doi.org/10.1016/j.jacadv.2023.100780
State	Published - Mar 2024

Keywords

COVID-19
anticoagulation
clinical trial
heparin
thrombosis

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine
Dentistry (miscellaneous)

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10.1016/j.jacadv.2023.100780

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Godoy, L. C., Neal, M. D., Goligher, E. C., Cushman, M., Houston, B. L., Bradbury, C. A., McQuilten, Z. K., Tritschler, T., Kahn, S. R., Berry, L. R., Lorenzi, E., Jensen, T., Higgins, A. M., Kornblith, L. Z., Berger, J. S., Gong, M. N., Paul, J. D., Castellucci, L. A., Le Gal, G., ... Lawler, P. R. (2024). Heparin Dose Intensity and Organ Support-Free Days in Patients Hospitalized for COVID-19. JACC: Advances, 3(3), Article 100780. https://doi.org/10.1016/j.jacadv.2023.100780

Godoy, LC, Neal, MD, Goligher, EC, Cushman, M, Houston, BL, Bradbury, CA, McQuilten, ZK, Tritschler, T, Kahn, SR, Berry, LR, Lorenzi, E, Jensen, T, Higgins, AM, Kornblith, LZ, Berger, JS, Gong, MN, Paul, JD, Castellucci, LA, Le Gal, G, Lother, SA, Rosenson, RS, Derde, LPG, Kumar, A, McVerry, BJ, Nicolau, JC, Leifer, E, Escobedo, J, Huang, DT, Reynolds, HR, Carrier, M, Kim, KS, Hunt, BJ, Slutsky, AS, Turgeon, AF, Webb, SA, McArthur, CJ, Farkouh, ME, Hochman, JS, Zarychanski, R & Lawler, PR 2024, 'Heparin Dose Intensity and Organ Support-Free Days in Patients Hospitalized for COVID-19', JACC: Advances, vol. 3, no. 3, 100780. https://doi.org/10.1016/j.jacadv.2023.100780

@article{6c485aaab7924e1ab4f203f26a65b42b,

title = "Heparin Dose Intensity and Organ Support-Free Days in Patients Hospitalized for COVID-19",

abstract = "Background: Clinical trials suggest that therapeutic-dose heparin may prevent critical illness and vascular complications due to COVID-19, but knowledge gaps exist regarding the efficacy of therapeutic heparin including its comparative effect relative to intermediate-dose anticoagulation. Objectives: The authors performed 2 complementary secondary analyses of a completed randomized clinical trial: 1) a prespecified per-protocol analysis; and 2) an exploratory dose-based analysis to compare the effect of therapeutic-dose heparin with low- and intermediate-dose heparin. Methods: Patients who received initial anticoagulation dosed consistently with randomization were included. The primary outcome was organ support-free days (OSFDs), a combination of in-hospital death and days free of organ support through day 21. Results: Among 2,860 participants, 1,761 (92.8%) noncritically ill and 857 (89.1%) critically ill patients were treated per-protocol. Among noncritically ill per-protocol patients, the posterior probability that therapeutic-dose heparin improved OSFDs as compared with usual care was 99.3% (median adjusted OR: 1.36; 95% credible interval [CrI]: 1.07-1.74). Therapeutic heparin had a high posterior probability of efficacy relative to both low- (94.6%; adjusted OR: 1.26; 95% CrI: 0.95-1.64) and intermediate- (99.8%; adjusted OR: 1.80; 95% CrI: 1.22-2.62) dose thromboprophylaxis. Among critically ill per-protocol patients, the posterior probability that therapeutic heparin improved outcomes was low. Conclusions: Among noncritically ill patients hospitalized for COVID-19 who were randomized to and initially received therapeutic-dose anticoagulation, heparin, compared with usual care, was associated with improved OSFDs, a combination of in-hospital death and days free of organ support. Therapeutic heparin appeared superior to both low- and intermediate-dose thromboprophylaxis.",

keywords = "COVID-19, anticoagulation, clinical trial, heparin, thrombosis",

author = "Godoy, {Lucas C.} and Neal, {Matthew D.} and Goligher, {Ewan C.} and Mary Cushman and Houston, {Brett L.} and Bradbury, {Charlotte A.} and McQuilten, {Zoe K.} and Tobias Tritschler and Kahn, {Susan R.} and Berry, {Lindsay R.} and Elizabeth Lorenzi and Tom Jensen and Higgins, {Alisa M.} and Kornblith, {Lucy Z.} and Berger, {Jeffrey S.} and Gong, {Michelle N.} and Paul, {Jonathan D.} and Castellucci, {Lana A.} and {Le Gal}, Gr{\'e}goire and Lother, {Sylvain A.} and Rosenson, {Robert S.} and Derde, {Lennie P.G.} and Anand Kumar and McVerry, {Bryan J.} and Nicolau, {Jose C.} and Eric Leifer and Jorge Escobedo and Huang, {David T.} and Reynolds, {Harmony R.} and Marc Carrier and Kim, {Keri S.} and Hunt, {Beverley J.} and Slutsky, {Arthur S.} and Turgeon, {Alexis F.} and Webb, {Steven A.} and McArthur, {Colin J.} and Farkouh, {Michael E.} and Hochman, {Judith S.} and Ryan Zarychanski and Lawler, {Patrick R.}",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors",

year = "2024",

month = mar,

doi = "10.1016/j.jacadv.2023.100780",

language = "English (US)",

volume = "3",

journal = "JACC: Advances",

issn = "2772-963X",

publisher = "Elsevier B.V.",

number = "3",

}

TY - JOUR

T1 - Heparin Dose Intensity and Organ Support-Free Days in Patients Hospitalized for COVID-19

AU - Godoy, Lucas C.

AU - Neal, Matthew D.

AU - Goligher, Ewan C.

AU - Cushman, Mary

AU - Houston, Brett L.

AU - Bradbury, Charlotte A.

AU - McQuilten, Zoe K.

AU - Tritschler, Tobias

AU - Kahn, Susan R.

AU - Berry, Lindsay R.

AU - Lorenzi, Elizabeth

AU - Jensen, Tom

AU - Higgins, Alisa M.

AU - Kornblith, Lucy Z.

AU - Berger, Jeffrey S.

AU - Gong, Michelle N.

AU - Paul, Jonathan D.

AU - Castellucci, Lana A.

AU - Le Gal, Grégoire

AU - Lother, Sylvain A.

AU - Rosenson, Robert S.

AU - Derde, Lennie P.G.

AU - Kumar, Anand

AU - McVerry, Bryan J.

AU - Nicolau, Jose C.

AU - Leifer, Eric

AU - Escobedo, Jorge

AU - Huang, David T.

AU - Reynolds, Harmony R.

AU - Carrier, Marc

AU - Kim, Keri S.

AU - Hunt, Beverley J.

AU - Slutsky, Arthur S.

AU - Turgeon, Alexis F.

AU - Webb, Steven A.

AU - McArthur, Colin J.

AU - Farkouh, Michael E.

AU - Hochman, Judith S.

AU - Zarychanski, Ryan

AU - Lawler, Patrick R.

PY - 2024/3

Y1 - 2024/3

N2 - Background: Clinical trials suggest that therapeutic-dose heparin may prevent critical illness and vascular complications due to COVID-19, but knowledge gaps exist regarding the efficacy of therapeutic heparin including its comparative effect relative to intermediate-dose anticoagulation. Objectives: The authors performed 2 complementary secondary analyses of a completed randomized clinical trial: 1) a prespecified per-protocol analysis; and 2) an exploratory dose-based analysis to compare the effect of therapeutic-dose heparin with low- and intermediate-dose heparin. Methods: Patients who received initial anticoagulation dosed consistently with randomization were included. The primary outcome was organ support-free days (OSFDs), a combination of in-hospital death and days free of organ support through day 21. Results: Among 2,860 participants, 1,761 (92.8%) noncritically ill and 857 (89.1%) critically ill patients were treated per-protocol. Among noncritically ill per-protocol patients, the posterior probability that therapeutic-dose heparin improved OSFDs as compared with usual care was 99.3% (median adjusted OR: 1.36; 95% credible interval [CrI]: 1.07-1.74). Therapeutic heparin had a high posterior probability of efficacy relative to both low- (94.6%; adjusted OR: 1.26; 95% CrI: 0.95-1.64) and intermediate- (99.8%; adjusted OR: 1.80; 95% CrI: 1.22-2.62) dose thromboprophylaxis. Among critically ill per-protocol patients, the posterior probability that therapeutic heparin improved outcomes was low. Conclusions: Among noncritically ill patients hospitalized for COVID-19 who were randomized to and initially received therapeutic-dose anticoagulation, heparin, compared with usual care, was associated with improved OSFDs, a combination of in-hospital death and days free of organ support. Therapeutic heparin appeared superior to both low- and intermediate-dose thromboprophylaxis.

AB - Background: Clinical trials suggest that therapeutic-dose heparin may prevent critical illness and vascular complications due to COVID-19, but knowledge gaps exist regarding the efficacy of therapeutic heparin including its comparative effect relative to intermediate-dose anticoagulation. Objectives: The authors performed 2 complementary secondary analyses of a completed randomized clinical trial: 1) a prespecified per-protocol analysis; and 2) an exploratory dose-based analysis to compare the effect of therapeutic-dose heparin with low- and intermediate-dose heparin. Methods: Patients who received initial anticoagulation dosed consistently with randomization were included. The primary outcome was organ support-free days (OSFDs), a combination of in-hospital death and days free of organ support through day 21. Results: Among 2,860 participants, 1,761 (92.8%) noncritically ill and 857 (89.1%) critically ill patients were treated per-protocol. Among noncritically ill per-protocol patients, the posterior probability that therapeutic-dose heparin improved OSFDs as compared with usual care was 99.3% (median adjusted OR: 1.36; 95% credible interval [CrI]: 1.07-1.74). Therapeutic heparin had a high posterior probability of efficacy relative to both low- (94.6%; adjusted OR: 1.26; 95% CrI: 0.95-1.64) and intermediate- (99.8%; adjusted OR: 1.80; 95% CrI: 1.22-2.62) dose thromboprophylaxis. Among critically ill per-protocol patients, the posterior probability that therapeutic heparin improved outcomes was low. Conclusions: Among noncritically ill patients hospitalized for COVID-19 who were randomized to and initially received therapeutic-dose anticoagulation, heparin, compared with usual care, was associated with improved OSFDs, a combination of in-hospital death and days free of organ support. Therapeutic heparin appeared superior to both low- and intermediate-dose thromboprophylaxis.

KW - COVID-19

KW - anticoagulation

KW - clinical trial

KW - heparin

KW - thrombosis

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UR - http://www.scopus.com/inward/citedby.url?scp=85183491776&partnerID=8YFLogxK

U2 - 10.1016/j.jacadv.2023.100780

DO - 10.1016/j.jacadv.2023.100780

M3 - Article

AN - SCOPUS:85183491776

SN - 2772-963X

VL - 3

JO - JACC: Advances

JF - JACC: Advances

IS - 3

M1 - 100780

ER -

Heparin Dose Intensity and Organ Support-Free Days in Patients Hospitalized for COVID-19

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