Association of Renin Angiotensin Aldosterone System Inhibitors and Outcomes of Hospitalized Patients with COVID-19

Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry Investigator Group

doi:10.1097/CCM.0000000000005627

Association of Renin Angiotensin Aldosterone System Inhibitors and Outcomes of Hospitalized Patients with COVID-19

Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry Investigator Group

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

Abstract

OBJECTIVES: To determine the association of prior use of renin-angiotensin-aldosterone system inhibitors (RAASIs) with mortality and outcomes in hospitalized patients with COVID-19. DESIGN: Retrospective observational study. SETTING: Multicenter, international COVID-19 registry. SUBJECTS: Adult hospitalized COVID-19 patients on antihypertensive agents (AHAs) prior to admission, admitted from March 31, 2020, to March 10, 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data were compared between three groups: patients on RAASIs only, other AHAs only, and those on both medications. Multivariable logistic and linear regressions were performed after controlling for prehospitalization characteristics to estimate the effect of RAASIs on mortality and other outcomes during hospitalization. Of 26,652 patients, 7,975 patients were on AHAs prior to hospitalization. Of these, 1,542 patients (19.3%) were on RAASIs only, 3,765 patients (47.2%) were on other AHAs only, and 2,668 (33.5%) patients were on both medications. Compared with those taking other AHAs only, patients on RAASIs only were younger (mean age 63.3 vs 66.9 yr; p < 0.0001), more often male (58.2% vs 52.4%; p = 0.0001) and more often White (55.1% vs 47.2%; p < 0.0001). After adjusting for age, gender, race, location, and comorbidities, patients on combination of RAASIs and other AHAs had higher in-hospital mortality than those on RAASIs only (odds ratio [OR] = 1.28; 95% CI [1.19-1.38]; p < 0.0001) and higher mortality than those on other AHAs only (OR = 1.09; 95% CI [1.03-1.15]; p = 0.0017). Patients on RAASIs only had lower mortality than those on other AHAs only (OR = 0.87; 95% CI [0.81-0.94]; p = 0.0003). Patients on ACEIs only had higher mortality compared with those on ARBs only (OR = 1.37; 95% CI [1.20-1.56]; p < 0.0001). CONCLUSIONS: Among patients hospitalized for COVID-19 who were taking AHAs, prior use of a combination of RAASIs and other AHAs was associated with higher in-hospital mortality than the use of RAASIs alone. When compared with ARBs, ACEIs were associated with signifcantly higher mortality in hospitalized COVID-19 patients.

Original language	English (US)
Pages (from-to)	E744-E758
Journal	Critical care medicine
Volume	50
Issue number	10
DOIs	https://doi.org/10.1097/CCM.0000000000005627
State	Published - Oct 1 2022

Bibliographical note

Funding Information:
Dr. Perkins received funding from TelmedIQ. Dr. Kaufman’s institution received funding from the Society of Critical Care Medicine, and she received funding from consulting for Mendaera. Dr. Christie’s institution received funding from Navicent Health Foundation. Ms. Boman, Drs. Kumar’s, Walkey’s, and Kashyap’s institutions received funding from the Gordon and Betty Moore Foundation. Ms. Boman, Drs. Kumar’s, and Kashyap’s institutions received funding from Janssen R & D. Dr. Aston’s institution received funding from the National Institutes of Health. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Funding Information:
Supported, in part, by National Institutes of Health/ National Center for Research Resources/National Center for Advancing Translational Sciences' Clinical and Translational Science Award Grant Number UL1 TR002377 (Research Electronic Data Capture), U54 GM104940 which funds the Louisiana Clinical and Translational Science Center Roadmap Scholars Award (to Dr. Denson), American Diabetes Association COVID-19 Research Award 7-20-COVID-053 (to Dr. Denson), the Society of Critical Care Medicine (to Dr. Denson), the Gordon and Betty Moore Foundation (to Dr. Denson), and Janssen Research & Development, LLC (to Drs. Boman, Kumar, and Kashyap).

Publisher Copyright:
Copyright © 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Keywords

COVID-19
antihypertensive agents
mortality
outcome
renin-angiotensin-aldosterone system inhibitors

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10.1097/CCM.0000000000005627

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Association of Renin Angiotensin Aldosterone System Inhibitors and Outcomes of Hospitalized Patients with COVID-19. / Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry Investigator Group.

In: Critical care medicine, Vol. 50, No. 10, 01.10.2022, p. E744-E758.

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

Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry Investigator Group 2022, 'Association of Renin Angiotensin Aldosterone System Inhibitors and Outcomes of Hospitalized Patients with COVID-19', Critical care medicine, vol. 50, no. 10, pp. E744-E758. https://doi.org/10.1097/CCM.0000000000005627

@article{fa69a187fee54d14a107da3c843b4ac9,

title = "Association of Renin Angiotensin Aldosterone System Inhibitors and Outcomes of Hospitalized Patients with COVID-19",

abstract = "OBJECTIVES: To determine the association of prior use of renin-angiotensin-aldosterone system inhibitors (RAASIs) with mortality and outcomes in hospitalized patients with COVID-19. DESIGN: Retrospective observational study. SETTING: Multicenter, international COVID-19 registry. SUBJECTS: Adult hospitalized COVID-19 patients on antihypertensive agents (AHAs) prior to admission, admitted from March 31, 2020, to March 10, 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data were compared between three groups: patients on RAASIs only, other AHAs only, and those on both medications. Multivariable logistic and linear regressions were performed after controlling for prehospitalization characteristics to estimate the effect of RAASIs on mortality and other outcomes during hospitalization. Of 26,652 patients, 7,975 patients were on AHAs prior to hospitalization. Of these, 1,542 patients (19.3%) were on RAASIs only, 3,765 patients (47.2%) were on other AHAs only, and 2,668 (33.5%) patients were on both medications. Compared with those taking other AHAs only, patients on RAASIs only were younger (mean age 63.3 vs 66.9 yr; p < 0.0001), more often male (58.2% vs 52.4%; p = 0.0001) and more often White (55.1% vs 47.2%; p < 0.0001). After adjusting for age, gender, race, location, and comorbidities, patients on combination of RAASIs and other AHAs had higher in-hospital mortality than those on RAASIs only (odds ratio [OR] = 1.28; 95% CI [1.19-1.38]; p < 0.0001) and higher mortality than those on other AHAs only (OR = 1.09; 95% CI [1.03-1.15]; p = 0.0017). Patients on RAASIs only had lower mortality than those on other AHAs only (OR = 0.87; 95% CI [0.81-0.94]; p = 0.0003). Patients on ACEIs only had higher mortality compared with those on ARBs only (OR = 1.37; 95% CI [1.20-1.56]; p < 0.0001). CONCLUSIONS: Among patients hospitalized for COVID-19 who were taking AHAs, prior use of a combination of RAASIs and other AHAs was associated with higher in-hospital mortality than the use of RAASIs alone. When compared with ARBs, ACEIs were associated with signifcantly higher mortality in hospitalized COVID-19 patients.",

keywords = "COVID-19, antihypertensive agents, mortality, outcome, renin-angiotensin-aldosterone system inhibitors",

author = "{Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry Investigator Group} and Neha Gupta and Lisa Settle and Brown, {Brent R.} and Armaignac, {Donna L.} and Michael Baram and Perkins, {Nicholas E.} and Margit Kaufman and Melamed, {Roman R.} and Christie, {Amy B.} and Danesh, {Valerie C.} and Denson, {Joshua L.} and Cheruku, {Sreekanth R.} and Karen Boman and Kumar, {Vishakha K.} and Vikas Bansal and Rahul Kashyap and Walkey, {Allan J.} and Domecq, {Juan P.} and Aston, {Christopher E.} and Mesland, {Jean Baptiste} and Pierre Henin and H{\'e}l{\`e}ne Petre and Isabelle Buelens and Gerard, {Anne Catherine} and Philippe Clevenbergh and Granado, {Rolando Claure Del} and Mercado, {Jose A.} and Esdenka Vega-Terrazas and Iturricha-Caceres, {Maria F.} and Ruben Garza and Eric Chu and Victoria Chan and Gavidia, {Oscar Y.} and Felipe Pachon and Sanchez, {Yeimy A.} and Danijel Kne{\v z}evi{\'c} and {El Kassas}, Mohamed and Mohamed Badr and Ahmed Tawheed and Hend Yahia and Dimitrios Kantas and Vasileios Koulouras and Estela Pineda and {Reyes Guillen}, {Gabina Mar{\'i}a} and Soto, {Helin Archaga} and {Vallecillo Lizardo}, {Ana Karen} and Tierney, {David M.} and Heneghan, {Julia A.} and Lexie Goertzen and McGonagill, {Patrick W.}",

note = "Funding Information: Dr. Perkins received funding from TelmedIQ. Dr. Kaufman{\textquoteright}s institution received funding from the Society of Critical Care Medicine, and she received funding from consulting for Mendaera. Dr. Christie{\textquoteright}s institution received funding from Navicent Health Foundation. Ms. Boman, Drs. Kumar{\textquoteright}s, Walkey{\textquoteright}s, and Kashyap{\textquoteright}s institutions received funding from the Gordon and Betty Moore Foundation. Ms. Boman, Drs. Kumar{\textquoteright}s, and Kashyap{\textquoteright}s institutions received funding from Janssen R & D. Dr. Aston{\textquoteright}s institution received funding from the National Institutes of Health. The remaining authors have disclosed that they do not have any potential conflicts of interest. Funding Information: Supported, in part, by National Institutes of Health/ National Center for Research Resources/National Center for Advancing Translational Sciences' Clinical and Translational Science Award Grant Number UL1 TR002377 (Research Electronic Data Capture), U54 GM104940 which funds the Louisiana Clinical and Translational Science Center Roadmap Scholars Award (to Dr. Denson), American Diabetes Association COVID-19 Research Award 7-20-COVID-053 (to Dr. Denson), the Society of Critical Care Medicine (to Dr. Denson), the Gordon and Betty Moore Foundation (to Dr. Denson), and Janssen Research & Development, LLC (to Drs. Boman, Kumar, and Kashyap). Publisher Copyright: Copyright {\textcopyright} 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.",

year = "2022",

month = oct,

day = "1",

doi = "10.1097/CCM.0000000000005627",

language = "English (US)",

volume = "50",

pages = "E744--E758",

journal = "Critical Care Medicine",

issn = "0090-3493",

publisher = "Lippincott Williams and Wilkins",

number = "10",

}

TY - JOUR

T1 - Association of Renin Angiotensin Aldosterone System Inhibitors and Outcomes of Hospitalized Patients with COVID-19

AU - Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry Investigator Group

AU - Gupta, Neha

AU - Settle, Lisa

AU - Brown, Brent R.

AU - Armaignac, Donna L.

AU - Baram, Michael

AU - Perkins, Nicholas E.

AU - Kaufman, Margit

AU - Melamed, Roman R.

AU - Christie, Amy B.

AU - Danesh, Valerie C.

AU - Denson, Joshua L.

AU - Cheruku, Sreekanth R.

AU - Boman, Karen

AU - Kumar, Vishakha K.

AU - Bansal, Vikas

AU - Kashyap, Rahul

AU - Walkey, Allan J.

AU - Domecq, Juan P.

AU - Aston, Christopher E.

AU - Mesland, Jean Baptiste

AU - Henin, Pierre

AU - Petre, Hélène

AU - Buelens, Isabelle

AU - Gerard, Anne Catherine

AU - Clevenbergh, Philippe

AU - Granado, Rolando Claure Del

AU - Mercado, Jose A.

AU - Vega-Terrazas, Esdenka

AU - Iturricha-Caceres, Maria F.

AU - Garza, Ruben

AU - Chu, Eric

AU - Chan, Victoria

AU - Gavidia, Oscar Y.

AU - Pachon, Felipe

AU - Sanchez, Yeimy A.

AU - Knežević, Danijel

AU - El Kassas, Mohamed

AU - Badr, Mohamed

AU - Tawheed, Ahmed

AU - Yahia, Hend

AU - Kantas, Dimitrios

AU - Koulouras, Vasileios

AU - Pineda, Estela

AU - Reyes Guillen, Gabina María

AU - Soto, Helin Archaga

AU - Vallecillo Lizardo, Ana Karen

AU - Tierney, David M.

AU - Heneghan, Julia A.

AU - Goertzen, Lexie

AU - McGonagill, Patrick W.

N1 - Funding Information: Dr. Perkins received funding from TelmedIQ. Dr. Kaufman’s institution received funding from the Society of Critical Care Medicine, and she received funding from consulting for Mendaera. Dr. Christie’s institution received funding from Navicent Health Foundation. Ms. Boman, Drs. Kumar’s, Walkey’s, and Kashyap’s institutions received funding from the Gordon and Betty Moore Foundation. Ms. Boman, Drs. Kumar’s, and Kashyap’s institutions received funding from Janssen R & D. Dr. Aston’s institution received funding from the National Institutes of Health. The remaining authors have disclosed that they do not have any potential conflicts of interest. Funding Information: Supported, in part, by National Institutes of Health/ National Center for Research Resources/National Center for Advancing Translational Sciences' Clinical and Translational Science Award Grant Number UL1 TR002377 (Research Electronic Data Capture), U54 GM104940 which funds the Louisiana Clinical and Translational Science Center Roadmap Scholars Award (to Dr. Denson), American Diabetes Association COVID-19 Research Award 7-20-COVID-053 (to Dr. Denson), the Society of Critical Care Medicine (to Dr. Denson), the Gordon and Betty Moore Foundation (to Dr. Denson), and Janssen Research & Development, LLC (to Drs. Boman, Kumar, and Kashyap). Publisher Copyright: Copyright © 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

PY - 2022/10/1

Y1 - 2022/10/1

N2 - OBJECTIVES: To determine the association of prior use of renin-angiotensin-aldosterone system inhibitors (RAASIs) with mortality and outcomes in hospitalized patients with COVID-19. DESIGN: Retrospective observational study. SETTING: Multicenter, international COVID-19 registry. SUBJECTS: Adult hospitalized COVID-19 patients on antihypertensive agents (AHAs) prior to admission, admitted from March 31, 2020, to March 10, 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data were compared between three groups: patients on RAASIs only, other AHAs only, and those on both medications. Multivariable logistic and linear regressions were performed after controlling for prehospitalization characteristics to estimate the effect of RAASIs on mortality and other outcomes during hospitalization. Of 26,652 patients, 7,975 patients were on AHAs prior to hospitalization. Of these, 1,542 patients (19.3%) were on RAASIs only, 3,765 patients (47.2%) were on other AHAs only, and 2,668 (33.5%) patients were on both medications. Compared with those taking other AHAs only, patients on RAASIs only were younger (mean age 63.3 vs 66.9 yr; p < 0.0001), more often male (58.2% vs 52.4%; p = 0.0001) and more often White (55.1% vs 47.2%; p < 0.0001). After adjusting for age, gender, race, location, and comorbidities, patients on combination of RAASIs and other AHAs had higher in-hospital mortality than those on RAASIs only (odds ratio [OR] = 1.28; 95% CI [1.19-1.38]; p < 0.0001) and higher mortality than those on other AHAs only (OR = 1.09; 95% CI [1.03-1.15]; p = 0.0017). Patients on RAASIs only had lower mortality than those on other AHAs only (OR = 0.87; 95% CI [0.81-0.94]; p = 0.0003). Patients on ACEIs only had higher mortality compared with those on ARBs only (OR = 1.37; 95% CI [1.20-1.56]; p < 0.0001). CONCLUSIONS: Among patients hospitalized for COVID-19 who were taking AHAs, prior use of a combination of RAASIs and other AHAs was associated with higher in-hospital mortality than the use of RAASIs alone. When compared with ARBs, ACEIs were associated with signifcantly higher mortality in hospitalized COVID-19 patients.

AB - OBJECTIVES: To determine the association of prior use of renin-angiotensin-aldosterone system inhibitors (RAASIs) with mortality and outcomes in hospitalized patients with COVID-19. DESIGN: Retrospective observational study. SETTING: Multicenter, international COVID-19 registry. SUBJECTS: Adult hospitalized COVID-19 patients on antihypertensive agents (AHAs) prior to admission, admitted from March 31, 2020, to March 10, 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data were compared between three groups: patients on RAASIs only, other AHAs only, and those on both medications. Multivariable logistic and linear regressions were performed after controlling for prehospitalization characteristics to estimate the effect of RAASIs on mortality and other outcomes during hospitalization. Of 26,652 patients, 7,975 patients were on AHAs prior to hospitalization. Of these, 1,542 patients (19.3%) were on RAASIs only, 3,765 patients (47.2%) were on other AHAs only, and 2,668 (33.5%) patients were on both medications. Compared with those taking other AHAs only, patients on RAASIs only were younger (mean age 63.3 vs 66.9 yr; p < 0.0001), more often male (58.2% vs 52.4%; p = 0.0001) and more often White (55.1% vs 47.2%; p < 0.0001). After adjusting for age, gender, race, location, and comorbidities, patients on combination of RAASIs and other AHAs had higher in-hospital mortality than those on RAASIs only (odds ratio [OR] = 1.28; 95% CI [1.19-1.38]; p < 0.0001) and higher mortality than those on other AHAs only (OR = 1.09; 95% CI [1.03-1.15]; p = 0.0017). Patients on RAASIs only had lower mortality than those on other AHAs only (OR = 0.87; 95% CI [0.81-0.94]; p = 0.0003). Patients on ACEIs only had higher mortality compared with those on ARBs only (OR = 1.37; 95% CI [1.20-1.56]; p < 0.0001). CONCLUSIONS: Among patients hospitalized for COVID-19 who were taking AHAs, prior use of a combination of RAASIs and other AHAs was associated with higher in-hospital mortality than the use of RAASIs alone. When compared with ARBs, ACEIs were associated with signifcantly higher mortality in hospitalized COVID-19 patients.

KW - COVID-19

KW - antihypertensive agents

KW - mortality

KW - outcome

KW - renin-angiotensin-aldosterone system inhibitors

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SN - 0090-3493

VL - 50

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JO - Critical Care Medicine

JF - Critical Care Medicine

IS - 10

ER -

Association of Renin Angiotensin Aldosterone System Inhibitors and Outcomes of Hospitalized Patients with COVID-19

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