Anticoagulation, Bleeding, Mortality, and Pathology in Hospitalized Patients With COVID-19

Girish N. Nadkarni; Anuradha Lala; Emilia Bagiella; Helena L. Chang; Pedro R. Moreno; Elisabet Pujadas; Varun Arvind; Sonali Bose; Alexander W. Charney; Martin D. Chen; Carlos Cordon-Cardo; Andrew S. Dunn; Michael E. Farkouh; Benjamin S. Glicksberg; Arash Kia; Roopa Kohli-Seth; Matthew A. Levin; Prem Timsina; Shan Zhao; Zahi A. Fayad; Valentin Fuster

doi:10.1016/j.jacc.2020.08.041

Anticoagulation, Bleeding, Mortality, and Pathology in Hospitalized Patients With COVID-19

Girish N. Nadkarni, Anuradha Lala, Emilia Bagiella, Helena L. Chang, Pedro R. Moreno, Elisabet Pujadas, Varun Arvind, Sonali Bose, Alexander W. Charney, Martin D. Chen, Carlos Cordon-Cardo, Andrew S. Dunn, Michael E. Farkouh, Benjamin S. Glicksberg, Arash Kia, Roopa Kohli-Seth, Matthew A. Levin, Prem Timsina, Shan Zhao, Zahi A. FayadValentin Fuster

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

324 Scopus citations

Abstract

Background: Thromboembolic disease is common in coronavirus disease-2019 (COVID-19). There is limited evidence on the association of in-hospital anticoagulation (AC) with outcomes and postmortem findings. Objectives: The purpose of this study was to examine association of AC with in-hospital outcomes and describe thromboembolic findings on autopsies. Methods: This retrospective analysis examined the association of AC with mortality, intubation, and major bleeding. Subanalyses were also conducted on the association of therapeutic versus prophylactic AC initiated ≤48 h from admission. Thromboembolic disease was contextualized by premortem AC among consecutive autopsies. Results: Among 4,389 patients, median age was 65 years with 44% women. Compared with no AC (n = 1,530; 34.9%), therapeutic AC (n = 900; 20.5%) and prophylactic AC (n = 1,959; 44.6%) were associated with lower in-hospital mortality (adjusted hazard ratio [aHR]: 0.53; 95% confidence interval [CI]: 0.45 to 0.62 and aHR: 0.50; 95% CI: 0.45 to 0.57, respectively), and intubation (aHR: 0.69; 95% CI: 0.51 to 0.94 and aHR: 0.72; 95% CI: 0.58 to 0.89, respectively). When initiated ≤48 h from admission, there was no statistically significant difference between therapeutic (n = 766) versus prophylactic AC (n = 1,860) (aHR: 0.86; 95% CI: 0.73 to 1.02; p = 0.08). Overall, 89 patients (2%) had major bleeding adjudicated by clinician review, with 27 of 900 (3.0%) on therapeutic, 33 of 1,959 (1.7%) on prophylactic, and 29 of 1,530 (1.9%) on no AC. Of 26 autopsies, 11 (42%) had thromboembolic disease not clinically suspected and 3 of 11 (27%) were on therapeutic AC. Conclusions: AC was associated with lower mortality and intubation among hospitalized COVID-19 patients. Compared with prophylactic AC, therapeutic AC was associated with lower mortality, although not statistically significant. Autopsies revealed frequent thromboembolic disease. These data may inform trials to determine optimal AC regimens.

Original language	English
Pages (from-to)	1815-1826
Number of pages	12
Journal	Journal of the American College of Cardiology
Volume	76
Issue number	16
DOIs	https://doi.org/10.1016/j.jacc.2020.08.041
State	Published - 20 Oct 2020

Keywords

COVID-19
anticoagulation
intubation
mortality

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10.1016/j.jacc.2020.08.041

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Nadkarni, G. N., Lala, A., Bagiella, E., Chang, H. L., Moreno, P. R., Pujadas, E., Arvind, V., Bose, S., Charney, A. W., Chen, M. D., Cordon-Cardo, C., Dunn, A. S., Farkouh, M. E., Glicksberg, B. S., Kia, A., Kohli-Seth, R., Levin, M. A., Timsina, P., Zhao, S., ... Fuster, V. (2020). Anticoagulation, Bleeding, Mortality, and Pathology in Hospitalized Patients With COVID-19. Journal of the American College of Cardiology, 76(16), 1815-1826. https://doi.org/10.1016/j.jacc.2020.08.041

@article{1e521591b4f043cdba1abf593fe19a47,

title = "Anticoagulation, Bleeding, Mortality, and Pathology in Hospitalized Patients With COVID-19",

abstract = "Background: Thromboembolic disease is common in coronavirus disease-2019 (COVID-19). There is limited evidence on the association of in-hospital anticoagulation (AC) with outcomes and postmortem findings. Objectives: The purpose of this study was to examine association of AC with in-hospital outcomes and describe thromboembolic findings on autopsies. Methods: This retrospective analysis examined the association of AC with mortality, intubation, and major bleeding. Subanalyses were also conducted on the association of therapeutic versus prophylactic AC initiated ≤48 h from admission. Thromboembolic disease was contextualized by premortem AC among consecutive autopsies. Results: Among 4,389 patients, median age was 65 years with 44% women. Compared with no AC (n = 1,530; 34.9%), therapeutic AC (n = 900; 20.5%) and prophylactic AC (n = 1,959; 44.6%) were associated with lower in-hospital mortality (adjusted hazard ratio [aHR]: 0.53; 95% confidence interval [CI]: 0.45 to 0.62 and aHR: 0.50; 95% CI: 0.45 to 0.57, respectively), and intubation (aHR: 0.69; 95% CI: 0.51 to 0.94 and aHR: 0.72; 95% CI: 0.58 to 0.89, respectively). When initiated ≤48 h from admission, there was no statistically significant difference between therapeutic (n = 766) versus prophylactic AC (n = 1,860) (aHR: 0.86; 95% CI: 0.73 to 1.02; p = 0.08). Overall, 89 patients (2%) had major bleeding adjudicated by clinician review, with 27 of 900 (3.0%) on therapeutic, 33 of 1,959 (1.7%) on prophylactic, and 29 of 1,530 (1.9%) on no AC. Of 26 autopsies, 11 (42%) had thromboembolic disease not clinically suspected and 3 of 11 (27%) were on therapeutic AC. Conclusions: AC was associated with lower mortality and intubation among hospitalized COVID-19 patients. Compared with prophylactic AC, therapeutic AC was associated with lower mortality, although not statistically significant. Autopsies revealed frequent thromboembolic disease. These data may inform trials to determine optimal AC regimens.",

keywords = "COVID-19, anticoagulation, intubation, mortality",

author = "Nadkarni, {Girish N.} and Anuradha Lala and Emilia Bagiella and Chang, {Helena L.} and Moreno, {Pedro R.} and Elisabet Pujadas and Varun Arvind and Sonali Bose and Charney, {Alexander W.} and Chen, {Martin D.} and Carlos Cordon-Cardo and Dunn, {Andrew S.} and Farkouh, {Michael E.} and Glicksberg, {Benjamin S.} and Arash Kia and Roopa Kohli-Seth and Levin, {Matthew A.} and Prem Timsina and Shan Zhao and Fayad, {Zahi A.} and Valentin Fuster",

note = "Funding Information: This study is funded by U54 TR001433-05 from the National Institutes of Health. The funding source had no role in the writing of the manuscript or the decision to submit it for publication. Dr. Nadkarni has received grants, personal fees, and nonfinancial support from Renalytix AI; has received nonfinancial support from Pensieve Health; and has received personal fees from AstraZeneca, BioVie, and GLG Consulting outside of the submitted work. Dr. Lala has received personal fees from Zoll outside of the submitted work. Dr. Dunn has received grants from Pfizer; and has received personal fees from Bristol Myers Squibb outside of the submitted work. Dr. Farkouh has received grants from Amgen, Novo Nordisk, and Novartis outside of the submitted work. Dr. Fayad has received grants from Daiichi-Sankyo, Amgen, Bristol Myers Squibb, and Siemens Healthineers; has received personal fees from Alexion, GlaxoSmithKline, and Trained Therapeutix Discovery outside of the submitted work; and has patents licensed to Trained Therapeutix Discovery. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Deepak L. Bhatt, MD, MPH, served as Guest Editor-in-Chief for this paper. Publisher Copyright: {\textcopyright} 2020",

year = "2020",

month = oct,

day = "20",

doi = "10.1016/j.jacc.2020.08.041",

language = "English",

volume = "76",

pages = "1815--1826",

journal = "Journal of the American College of Cardiology",

issn = "0735-1097",

publisher = "Elsevier USA",

number = "16",

}

Nadkarni, GN , Lala, A , Bagiella, E, Chang, HL, Moreno, PR, Pujadas, E, Arvind, V, Bose, S , Charney, AW, Chen, MD, Cordon-Cardo, C, Dunn, AS, Farkouh, ME, Glicksberg, BS , Kia, A , Kohli-Seth, R , Levin, MA, Timsina, P, Zhao, S, Fayad, ZA & Fuster, V 2020, 'Anticoagulation, Bleeding, Mortality, and Pathology in Hospitalized Patients With COVID-19', Journal of the American College of Cardiology, vol. 76, no. 16, pp. 1815-1826. https://doi.org/10.1016/j.jacc.2020.08.041

TY - JOUR

T1 - Anticoagulation, Bleeding, Mortality, and Pathology in Hospitalized Patients With COVID-19

AU - Nadkarni, Girish N.

AU - Lala, Anuradha

AU - Bagiella, Emilia

AU - Chang, Helena L.

AU - Moreno, Pedro R.

AU - Pujadas, Elisabet

AU - Arvind, Varun

AU - Bose, Sonali

AU - Charney, Alexander W.

AU - Chen, Martin D.

AU - Cordon-Cardo, Carlos

AU - Dunn, Andrew S.

AU - Farkouh, Michael E.

AU - Glicksberg, Benjamin S.

AU - Kia, Arash

AU - Kohli-Seth, Roopa

AU - Levin, Matthew A.

AU - Timsina, Prem

AU - Zhao, Shan

AU - Fayad, Zahi A.

AU - Fuster, Valentin

N1 - Funding Information: This study is funded by U54 TR001433-05 from the National Institutes of Health. The funding source had no role in the writing of the manuscript or the decision to submit it for publication. Dr. Nadkarni has received grants, personal fees, and nonfinancial support from Renalytix AI; has received nonfinancial support from Pensieve Health; and has received personal fees from AstraZeneca, BioVie, and GLG Consulting outside of the submitted work. Dr. Lala has received personal fees from Zoll outside of the submitted work. Dr. Dunn has received grants from Pfizer; and has received personal fees from Bristol Myers Squibb outside of the submitted work. Dr. Farkouh has received grants from Amgen, Novo Nordisk, and Novartis outside of the submitted work. Dr. Fayad has received grants from Daiichi-Sankyo, Amgen, Bristol Myers Squibb, and Siemens Healthineers; has received personal fees from Alexion, GlaxoSmithKline, and Trained Therapeutix Discovery outside of the submitted work; and has patents licensed to Trained Therapeutix Discovery. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Deepak L. Bhatt, MD, MPH, served as Guest Editor-in-Chief for this paper. Publisher Copyright: © 2020

PY - 2020/10/20

Y1 - 2020/10/20

N2 - Background: Thromboembolic disease is common in coronavirus disease-2019 (COVID-19). There is limited evidence on the association of in-hospital anticoagulation (AC) with outcomes and postmortem findings. Objectives: The purpose of this study was to examine association of AC with in-hospital outcomes and describe thromboembolic findings on autopsies. Methods: This retrospective analysis examined the association of AC with mortality, intubation, and major bleeding. Subanalyses were also conducted on the association of therapeutic versus prophylactic AC initiated ≤48 h from admission. Thromboembolic disease was contextualized by premortem AC among consecutive autopsies. Results: Among 4,389 patients, median age was 65 years with 44% women. Compared with no AC (n = 1,530; 34.9%), therapeutic AC (n = 900; 20.5%) and prophylactic AC (n = 1,959; 44.6%) were associated with lower in-hospital mortality (adjusted hazard ratio [aHR]: 0.53; 95% confidence interval [CI]: 0.45 to 0.62 and aHR: 0.50; 95% CI: 0.45 to 0.57, respectively), and intubation (aHR: 0.69; 95% CI: 0.51 to 0.94 and aHR: 0.72; 95% CI: 0.58 to 0.89, respectively). When initiated ≤48 h from admission, there was no statistically significant difference between therapeutic (n = 766) versus prophylactic AC (n = 1,860) (aHR: 0.86; 95% CI: 0.73 to 1.02; p = 0.08). Overall, 89 patients (2%) had major bleeding adjudicated by clinician review, with 27 of 900 (3.0%) on therapeutic, 33 of 1,959 (1.7%) on prophylactic, and 29 of 1,530 (1.9%) on no AC. Of 26 autopsies, 11 (42%) had thromboembolic disease not clinically suspected and 3 of 11 (27%) were on therapeutic AC. Conclusions: AC was associated with lower mortality and intubation among hospitalized COVID-19 patients. Compared with prophylactic AC, therapeutic AC was associated with lower mortality, although not statistically significant. Autopsies revealed frequent thromboembolic disease. These data may inform trials to determine optimal AC regimens.

AB - Background: Thromboembolic disease is common in coronavirus disease-2019 (COVID-19). There is limited evidence on the association of in-hospital anticoagulation (AC) with outcomes and postmortem findings. Objectives: The purpose of this study was to examine association of AC with in-hospital outcomes and describe thromboembolic findings on autopsies. Methods: This retrospective analysis examined the association of AC with mortality, intubation, and major bleeding. Subanalyses were also conducted on the association of therapeutic versus prophylactic AC initiated ≤48 h from admission. Thromboembolic disease was contextualized by premortem AC among consecutive autopsies. Results: Among 4,389 patients, median age was 65 years with 44% women. Compared with no AC (n = 1,530; 34.9%), therapeutic AC (n = 900; 20.5%) and prophylactic AC (n = 1,959; 44.6%) were associated with lower in-hospital mortality (adjusted hazard ratio [aHR]: 0.53; 95% confidence interval [CI]: 0.45 to 0.62 and aHR: 0.50; 95% CI: 0.45 to 0.57, respectively), and intubation (aHR: 0.69; 95% CI: 0.51 to 0.94 and aHR: 0.72; 95% CI: 0.58 to 0.89, respectively). When initiated ≤48 h from admission, there was no statistically significant difference between therapeutic (n = 766) versus prophylactic AC (n = 1,860) (aHR: 0.86; 95% CI: 0.73 to 1.02; p = 0.08). Overall, 89 patients (2%) had major bleeding adjudicated by clinician review, with 27 of 900 (3.0%) on therapeutic, 33 of 1,959 (1.7%) on prophylactic, and 29 of 1,530 (1.9%) on no AC. Of 26 autopsies, 11 (42%) had thromboembolic disease not clinically suspected and 3 of 11 (27%) were on therapeutic AC. Conclusions: AC was associated with lower mortality and intubation among hospitalized COVID-19 patients. Compared with prophylactic AC, therapeutic AC was associated with lower mortality, although not statistically significant. Autopsies revealed frequent thromboembolic disease. These data may inform trials to determine optimal AC regimens.

KW - COVID-19

KW - anticoagulation

KW - intubation

KW - mortality

UR - http://www.scopus.com/inward/record.url?scp=85092086852&partnerID=8YFLogxK

U2 - 10.1016/j.jacc.2020.08.041

DO - 10.1016/j.jacc.2020.08.041

M3 - Article

C2 - 32860872

AN - SCOPUS:85092086852

SN - 0735-1097

VL - 76

SP - 1815

EP - 1826

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

IS - 16

ER -

Anticoagulation, Bleeding, Mortality, and Pathology in Hospitalized Patients With COVID-19

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