Effect of therapeutic-dose heparin on severe acute kidney injury and death in noncritically ill patients hospitalized for COVID-19: a prespecified secondary analysis of the ACTIV4a and ATTACC randomized trial

Nathaniel R. Smilowitz; Erinn M. Hade; Lucy Z. Kornblith; Lana A. Castellucci; Mary Cushman; Michael Farkouh; Michelle N. Gong; Anna Heath; Beverly J. Hunt; Keri S. Kim; Andrei Kindzelski; Patrick Lawler; David E. Leaf; Ewan Goligher; Eric S. Leifer; Bryan J. McVerry; Harmony R. Reynolds; Ryan Zarychanski; Judith S. Hochman; Matthew D. Neal; Jeffrey S. Berger

doi:10.1016/j.rpth.2023.102167

Effect of therapeutic-dose heparin on severe acute kidney injury and death in noncritically ill patients hospitalized for COVID-19: a prespecified secondary analysis of the ACTIV4a and ATTACC randomized trial

Nathaniel R. Smilowitz, Erinn M. Hade, Lucy Z. Kornblith, Lana A. Castellucci, Mary Cushman, Michael Farkouh, Michelle N. Gong, Anna Heath, Beverly J. Hunt, Keri S. Kim, Andrei Kindzelski, Patrick Lawler, David E. Leaf, Ewan Goligher, Eric S. Leifer, Bryan J. McVerry, Harmony R. Reynolds, Ryan Zarychanski, Judith S. Hochman, Matthew D. NealJeffrey S. Berger

Medicine

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

3 Scopus citations

Abstract

Background: Acute kidney injury (AKI) in patients with COVID-19 is partly mediated by thromboinflammation. In noncritically ill patients with COVID-19, therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support. Objectives: We investigated whether therapeutic-dose heparin reduces the incidence of AKI or death in noncritically ill patients hospitalized for COVID-19. Methods: We report a prespecified secondary analysis of the ACTIV4a and ATTACC open-label, multiplatform randomized trial of therapeutic-dose heparin vs usual-care pharmacologic thromboprophylaxis on the incidence of severe AKI (≥2-fold increase in serum creatinine or initiation of kidney replacement therapy (KDIGO stage 2 or 3) or all-cause mortality in noncritically ill patients hospitalized for COVID-19. Bayesian statistical models were adjusted for age, sex, D-dimer, enrollment period, country, site, and platform. Results: Among 1922 enrolled, 23 were excluded due to pre-existing end stage kidney disease and 205 were missing baseline or follow-up creatinine measurements. Severe AKI or death occurred in 4.4% participants assigned to therapeutic-dose heparin and 5.5% assigned to thromboprophylaxis (adjusted relative risk [aRR]: 0.72; 95% credible interval (CrI): 0.47, 1.10); the posterior probability of superiority for therapeutic-dose heparin (relative risk < 1.0) was 93.6%. Therapeutic-dose heparin was associated with a 97.7% probability of superiority to reduce the composite of stage 3 AKI or death (3.1% vs 4.6%; aRR: 0.64; 95% CrI: 0.40, 0.99) compared to thromboprophylaxis. Conclusion: Therapeutic-dose heparin was associated with a high probability of superiority to reduce the incidence of in-hospital severe AKI or death in patients hospitalized for COVID-19.

Original language	English (US)
Article number	102167
Journal	Research and Practice in Thrombosis and Haemostasis
Volume	7
Issue number	6
DOIs	https://doi.org/10.1016/j.rpth.2023.102167
State	Published - Aug 2023

Keywords

COVID-19
acute kidney injury
anticoagulants
death
heparin
kidney diseases
mortality

ASJC Scopus subject areas

Hematology

Access to Document

10.1016/j.rpth.2023.102167

Fingerprint

Dive into the research topics of 'Effect of therapeutic-dose heparin on severe acute kidney injury and death in noncritically ill patients hospitalized for COVID-19: a prespecified secondary analysis of the ACTIV4a and ATTACC randomized trial'. Together they form a unique fingerprint.

Cite this

Smilowitz, N. R., Hade, E. M., Kornblith, L. Z., Castellucci, L. A., Cushman, M., Farkouh, M., Gong, M. N., Heath, A., Hunt, B. J., Kim, K. S., Kindzelski, A., Lawler, P., Leaf, D. E., Goligher, E., Leifer, E. S., McVerry, B. J., Reynolds, H. R., Zarychanski, R., Hochman, J. S., ... Berger, J. S. (2023). Effect of therapeutic-dose heparin on severe acute kidney injury and death in noncritically ill patients hospitalized for COVID-19: a prespecified secondary analysis of the ACTIV4a and ATTACC randomized trial. Research and Practice in Thrombosis and Haemostasis, 7(6), Article 102167. https://doi.org/10.1016/j.rpth.2023.102167

Effect of therapeutic-dose heparin on severe acute kidney injury and death in noncritically ill patients hospitalized for COVID-19: a prespecified secondary analysis of the ACTIV4a and ATTACC randomized trial. / Smilowitz, Nathaniel R.; Hade, Erinn M.; Kornblith, Lucy Z. et al.
In: Research and Practice in Thrombosis and Haemostasis, Vol. 7, No. 6, 102167, 08.2023.

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

Smilowitz, NR, Hade, EM, Kornblith, LZ, Castellucci, LA, Cushman, M, Farkouh, M, Gong, MN, Heath, A, Hunt, BJ, Kim, KS, Kindzelski, A, Lawler, P, Leaf, DE, Goligher, E, Leifer, ES, McVerry, BJ, Reynolds, HR, Zarychanski, R, Hochman, JS, Neal, MD & Berger, JS 2023, 'Effect of therapeutic-dose heparin on severe acute kidney injury and death in noncritically ill patients hospitalized for COVID-19: a prespecified secondary analysis of the ACTIV4a and ATTACC randomized trial', Research and Practice in Thrombosis and Haemostasis, vol. 7, no. 6, 102167. https://doi.org/10.1016/j.rpth.2023.102167

Smilowitz NR, Hade EM, Kornblith LZ, Castellucci LA, Cushman M, Farkouh M et al. Effect of therapeutic-dose heparin on severe acute kidney injury and death in noncritically ill patients hospitalized for COVID-19: a prespecified secondary analysis of the ACTIV4a and ATTACC randomized trial. Research and Practice in Thrombosis and Haemostasis. 2023 Aug;7(6):102167. doi: 10.1016/j.rpth.2023.102167

@article{4bbea21d7e7a4dee9eb7653141c71605,

title = "Effect of therapeutic-dose heparin on severe acute kidney injury and death in noncritically ill patients hospitalized for COVID-19: a prespecified secondary analysis of the ACTIV4a and ATTACC randomized trial",

abstract = "Background: Acute kidney injury (AKI) in patients with COVID-19 is partly mediated by thromboinflammation. In noncritically ill patients with COVID-19, therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support. Objectives: We investigated whether therapeutic-dose heparin reduces the incidence of AKI or death in noncritically ill patients hospitalized for COVID-19. Methods: We report a prespecified secondary analysis of the ACTIV4a and ATTACC open-label, multiplatform randomized trial of therapeutic-dose heparin vs usual-care pharmacologic thromboprophylaxis on the incidence of severe AKI (≥2-fold increase in serum creatinine or initiation of kidney replacement therapy (KDIGO stage 2 or 3) or all-cause mortality in noncritically ill patients hospitalized for COVID-19. Bayesian statistical models were adjusted for age, sex, D-dimer, enrollment period, country, site, and platform. Results: Among 1922 enrolled, 23 were excluded due to pre-existing end stage kidney disease and 205 were missing baseline or follow-up creatinine measurements. Severe AKI or death occurred in 4.4% participants assigned to therapeutic-dose heparin and 5.5% assigned to thromboprophylaxis (adjusted relative risk [aRR]: 0.72; 95% credible interval (CrI): 0.47, 1.10); the posterior probability of superiority for therapeutic-dose heparin (relative risk < 1.0) was 93.6%. Therapeutic-dose heparin was associated with a 97.7% probability of superiority to reduce the composite of stage 3 AKI or death (3.1% vs 4.6%; aRR: 0.64; 95% CrI: 0.40, 0.99) compared to thromboprophylaxis. Conclusion: Therapeutic-dose heparin was associated with a high probability of superiority to reduce the incidence of in-hospital severe AKI or death in patients hospitalized for COVID-19.",

keywords = "COVID-19, acute kidney injury, anticoagulants, death, heparin, kidney diseases, mortality",

author = "Smilowitz, {Nathaniel R.} and Hade, {Erinn M.} and Kornblith, {Lucy Z.} and Castellucci, {Lana A.} and Mary Cushman and Michael Farkouh and Gong, {Michelle N.} and Anna Heath and Hunt, {Beverly J.} and Kim, {Keri S.} and Andrei Kindzelski and Patrick Lawler and Leaf, {David E.} and Ewan Goligher and Leifer, {Eric S.} and McVerry, {Bryan J.} and Reynolds, {Harmony R.} and Ryan Zarychanski and Hochman, {Judith S.} and Neal, {Matthew D.} and Berger, {Jeffrey S.}",

note = "Publisher Copyright: {\textcopyright} 2023",

year = "2023",

month = aug,

doi = "10.1016/j.rpth.2023.102167",

language = "English (US)",

volume = "7",

journal = "Research and Practice in Thrombosis and Haemostasis",

issn = "2475-0379",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "6",

}

TY - JOUR

T1 - Effect of therapeutic-dose heparin on severe acute kidney injury and death in noncritically ill patients hospitalized for COVID-19

T2 - a prespecified secondary analysis of the ACTIV4a and ATTACC randomized trial

AU - Smilowitz, Nathaniel R.

AU - Hade, Erinn M.

AU - Kornblith, Lucy Z.

AU - Castellucci, Lana A.

AU - Cushman, Mary

AU - Farkouh, Michael

AU - Gong, Michelle N.

AU - Heath, Anna

AU - Hunt, Beverly J.

AU - Kim, Keri S.

AU - Kindzelski, Andrei

AU - Lawler, Patrick

AU - Leaf, David E.

AU - Goligher, Ewan

AU - Leifer, Eric S.

AU - McVerry, Bryan J.

AU - Reynolds, Harmony R.

AU - Zarychanski, Ryan

AU - Hochman, Judith S.

AU - Neal, Matthew D.

AU - Berger, Jeffrey S.

PY - 2023/8

Y1 - 2023/8

N2 - Background: Acute kidney injury (AKI) in patients with COVID-19 is partly mediated by thromboinflammation. In noncritically ill patients with COVID-19, therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support. Objectives: We investigated whether therapeutic-dose heparin reduces the incidence of AKI or death in noncritically ill patients hospitalized for COVID-19. Methods: We report a prespecified secondary analysis of the ACTIV4a and ATTACC open-label, multiplatform randomized trial of therapeutic-dose heparin vs usual-care pharmacologic thromboprophylaxis on the incidence of severe AKI (≥2-fold increase in serum creatinine or initiation of kidney replacement therapy (KDIGO stage 2 or 3) or all-cause mortality in noncritically ill patients hospitalized for COVID-19. Bayesian statistical models were adjusted for age, sex, D-dimer, enrollment period, country, site, and platform. Results: Among 1922 enrolled, 23 were excluded due to pre-existing end stage kidney disease and 205 were missing baseline or follow-up creatinine measurements. Severe AKI or death occurred in 4.4% participants assigned to therapeutic-dose heparin and 5.5% assigned to thromboprophylaxis (adjusted relative risk [aRR]: 0.72; 95% credible interval (CrI): 0.47, 1.10); the posterior probability of superiority for therapeutic-dose heparin (relative risk < 1.0) was 93.6%. Therapeutic-dose heparin was associated with a 97.7% probability of superiority to reduce the composite of stage 3 AKI or death (3.1% vs 4.6%; aRR: 0.64; 95% CrI: 0.40, 0.99) compared to thromboprophylaxis. Conclusion: Therapeutic-dose heparin was associated with a high probability of superiority to reduce the incidence of in-hospital severe AKI or death in patients hospitalized for COVID-19.

AB - Background: Acute kidney injury (AKI) in patients with COVID-19 is partly mediated by thromboinflammation. In noncritically ill patients with COVID-19, therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support. Objectives: We investigated whether therapeutic-dose heparin reduces the incidence of AKI or death in noncritically ill patients hospitalized for COVID-19. Methods: We report a prespecified secondary analysis of the ACTIV4a and ATTACC open-label, multiplatform randomized trial of therapeutic-dose heparin vs usual-care pharmacologic thromboprophylaxis on the incidence of severe AKI (≥2-fold increase in serum creatinine or initiation of kidney replacement therapy (KDIGO stage 2 or 3) or all-cause mortality in noncritically ill patients hospitalized for COVID-19. Bayesian statistical models were adjusted for age, sex, D-dimer, enrollment period, country, site, and platform. Results: Among 1922 enrolled, 23 were excluded due to pre-existing end stage kidney disease and 205 were missing baseline or follow-up creatinine measurements. Severe AKI or death occurred in 4.4% participants assigned to therapeutic-dose heparin and 5.5% assigned to thromboprophylaxis (adjusted relative risk [aRR]: 0.72; 95% credible interval (CrI): 0.47, 1.10); the posterior probability of superiority for therapeutic-dose heparin (relative risk < 1.0) was 93.6%. Therapeutic-dose heparin was associated with a 97.7% probability of superiority to reduce the composite of stage 3 AKI or death (3.1% vs 4.6%; aRR: 0.64; 95% CrI: 0.40, 0.99) compared to thromboprophylaxis. Conclusion: Therapeutic-dose heparin was associated with a high probability of superiority to reduce the incidence of in-hospital severe AKI or death in patients hospitalized for COVID-19.

KW - COVID-19

KW - acute kidney injury

KW - anticoagulants

KW - death

KW - heparin

KW - kidney diseases

KW - mortality

UR - http://www.scopus.com/inward/record.url?scp=85171346310&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85171346310&partnerID=8YFLogxK

U2 - 10.1016/j.rpth.2023.102167

DO - 10.1016/j.rpth.2023.102167

M3 - Article

AN - SCOPUS:85171346310

SN - 2475-0379

VL - 7

JO - Research and Practice in Thrombosis and Haemostasis

JF - Research and Practice in Thrombosis and Haemostasis

IS - 6

M1 - 102167

ER -

Effect of therapeutic-dose heparin on severe acute kidney injury and death in noncritically ill patients hospitalized for COVID-19: a prespecified secondary analysis of the ACTIV4a and ATTACC randomized trial

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this