TY - JOUR
T1 - Angiotensin Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors in COVID-19
T2 - Meta-analysis/Meta-regression Adjusted for Confounding Factors
AU - ARBs CORONA
AU - Lee, Terry
AU - Cau, Alessandro
AU - Cheng, Matthew Pellan
AU - Levin, Adeera
AU - Lee, Todd C.
AU - Vinh, Donald C.
AU - Lamontagne, Francois
AU - Singer, Joel
AU - Walley, Keith R.
AU - Murthy, Srinivas
AU - Patrick, David
AU - Rewa, Oleksa G.
AU - Winston, Brent W.
AU - Marshall, John
AU - Boyd, John
AU - Tran, Karen
AU - Kalil, Andre C.
AU - Mcculoh, Russell
AU - Fowler, Robert
AU - Luther, James M.
AU - Russell, James A.
N1 - Funding Information:
This work was supported by the Canadian Institutes of Health Research 439993.
Funding Information:
We thank the patients and families who participated in the ARBs CORONA I study, which has increased our understanding of COVID-19. We also thank the many dedicated clinicians (doctors, nurses, therapists, and others) who cared for these patients and comforted their families. We also thank the investigators in the ARBs CORONA program for their ongoing support and tireless collaboration (Supplemental Appendix S3). This work was supported by the Canadian Institutes of Health Research 439993. Dr Russell reports patents owned by the University of British Columbia (UBC) that are related to the use of PCSK9 inhibitor(s) in sepsis and to the use of vasopressin in septic shock. Dr Russell is an inventor on these patents. Dr Russell was a founder, director, and shareholder in Cyon Therapeutics Inc. and is a shareholder in Molecular You Corp. Dr Russell reports receiving consulting fees in the last 3 years from: (i) Asahi Kesai Pharmaceuticals of America (AKPA; was developing recombinant thrombomodulin in sepsis); (ii) SIB Therapeutics LLC (developing a sepsis drug); and (iii) Ferring Pharmaceuticals (manufactures vasopressin and is developing selepressin). Dr Russell is no longer actively consulting for the following: (iv) La Jolla Pharmaceuticals (developing angiotensin II; Dr Russell chaired the data and safety monitoring board of a trial of angiotensin II from 2015 to 2017); and (v) PAR Pharma (sells prepared bags of vasopressin). Dr Russell reports having received an investigator-initiated grant from Grifols (entitled ?Is HBP a mechanism of albumin's efficacy in human septic shock??) that was provided to and administered by UBC. Dr Cheng reports grants from McGill Interdisciplinary Initiative in Infection and Immunity, and grants from the Canadian Institutes of Health Research, during the conduct of the study; personal fees from GEn1E Lifesciences (as a member of the Scientific Advisory Board), and personal fees from nplex biosciences (as a member of the scientific advisory board), outside the submitted work. Dr Todd Lee receives research salary support from the Fonds de recherche du Qu?bec?Sant?. Dr Murthy receives research salary support from Innovative Medicines Canada. Dr Rewa has received consulting fees from Baxter Healthcare Inc. Dr Walley reports a patent owned by UBC that is related to the use of PCSK9 inhibitor(s) in sepsis. Dr Walley is an inventor on this patent. Dr Walley was a founder, director, and shareholder in Cyon Therapeutics Inc.
Funding Information:
Dr Russell reports patents owned by the University of British Columbia (UBC) that are related to the use of PCSK9 inhibitor(s) in sepsis and to the use of vasopressin in septic shock. Dr Russell is an inventor on these patents. Dr Russell was a founder, director, and shareholder in Cyon Therapeutics Inc. and is a shareholder in Molecular You Corp. Dr Russell reports receiving consulting fees in the last 3 years from: (i) Asahi Kesai Pharmaceuticals of America (AKPA; was developing recombinant thrombomodulin in sepsis); (ii) SIB Therapeutics LLC (developing a sepsis drug); and (iii) Ferring Pharmaceuticals (manufactures vasopressin and is developing selepressin). Dr Russell is no longer actively consulting for the following: (iv) La Jolla Pharmaceuticals (developing angiotensin II; Dr Russell chaired the data and safety monitoring board of a trial of angiotensin II from 2015 to 2017); and (v) PAR Pharma (sells prepared bags of vasopressin). Dr Russell reports having received an investigator-initiated grant from Grifols (entitled “Is HBP a mechanism of albumin's efficacy in human septic shock?”) that was provided to and administered by UBC. Dr Cheng reports grants from McGill Interdisciplinary Initiative in Infection and Immunity, and grants from the Canadian Institutes of Health Research, during the conduct of the study; personal fees from GEn1E Lifesciences (as a member of the Scientific Advisory Board), and personal fees from nplex biosciences (as a member of the scientific advisory board), outside the submitted work. Dr Todd Lee receives research salary support from the Fonds de recherche du Québec—Santé. Dr Murthy receives research salary support from Innovative Medicines Canada. Dr Rewa has received consulting fees from Baxter Healthcare Inc. Dr Walley reports a patent owned by UBC that is related to the use of PCSK9 inhibitor(s) in sepsis. Dr Walley is an inventor on this patent. Dr Walley was a founder, director, and shareholder in Cyon Therapeutics Inc.
Publisher Copyright:
© 2021 The Authors
PY - 2021/7
Y1 - 2021/7
N2 - Background: Angiotensin receptor blockers (ARBs) and/or angiotensin-converting enzyme (ACE) inhibitors could alter mortality from coronavirus disease 2019 (COVID-19), but existing meta-analyses that combined crude and adjusted results may be confounded by the fact that comorbidities are more common in ARB/ACE inhibitor users. Methods: We searched PubMed/MEDLINE/Embase for cohort studies and meta-analyses reporting mortality by preexisting ARB/ACE inhibitor treatment in hospitalized COVID-19 patients. Random effects meta-regression was used to compute pooled odds ratios for mortality adjusted for imbalance in age, sex, and prevalence of cardiovascular disease, hypertension, diabetes mellitus, and chronic kidney disease between users and nonusers of ARBs/ACE inhibitors at the study level during data synthesis. Results: In 30 included studies of 17,281 patients, 22%, 68%, 25%, and 11% had cardiovascular disease, hypertension, diabetes mellitus, and chronic kidney disease. ARB/ACE inhibitor use was associated with significantly lower mortality after controlling for potential confounding factors (odds ratio 0.77 [95% confidence interval: 0.62, 0.96]). In contrast, meta-analysis of ARB/ACE inhibitor use was not significantly associated with mortality when all studies were combined with no adjustment made for confounders (0.87 [95% confidence interval: 0.71, 1.08]). Conclusions: ARB/ACE inhibitor use was associated with decreased mortality in cohorts of COVID-19 patients after adjusting for age, sex, cardiovascular disease, hypertension, diabetes, and chronic kidney disease. Unadjusted meta-analyses may not be appropriate for determining whether ARBs/ACE inhibitors are associated with mortality from COVID-19 because of indication bias.
AB - Background: Angiotensin receptor blockers (ARBs) and/or angiotensin-converting enzyme (ACE) inhibitors could alter mortality from coronavirus disease 2019 (COVID-19), but existing meta-analyses that combined crude and adjusted results may be confounded by the fact that comorbidities are more common in ARB/ACE inhibitor users. Methods: We searched PubMed/MEDLINE/Embase for cohort studies and meta-analyses reporting mortality by preexisting ARB/ACE inhibitor treatment in hospitalized COVID-19 patients. Random effects meta-regression was used to compute pooled odds ratios for mortality adjusted for imbalance in age, sex, and prevalence of cardiovascular disease, hypertension, diabetes mellitus, and chronic kidney disease between users and nonusers of ARBs/ACE inhibitors at the study level during data synthesis. Results: In 30 included studies of 17,281 patients, 22%, 68%, 25%, and 11% had cardiovascular disease, hypertension, diabetes mellitus, and chronic kidney disease. ARB/ACE inhibitor use was associated with significantly lower mortality after controlling for potential confounding factors (odds ratio 0.77 [95% confidence interval: 0.62, 0.96]). In contrast, meta-analysis of ARB/ACE inhibitor use was not significantly associated with mortality when all studies were combined with no adjustment made for confounders (0.87 [95% confidence interval: 0.71, 1.08]). Conclusions: ARB/ACE inhibitor use was associated with decreased mortality in cohorts of COVID-19 patients after adjusting for age, sex, cardiovascular disease, hypertension, diabetes, and chronic kidney disease. Unadjusted meta-analyses may not be appropriate for determining whether ARBs/ACE inhibitors are associated with mortality from COVID-19 because of indication bias.
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U2 - 10.1016/j.cjco.2021.03.001
DO - 10.1016/j.cjco.2021.03.001
M3 - Review article
C2 - 33842874
AN - SCOPUS:85109437272
VL - 3
SP - 965
EP - 975
JO - CJC Open
JF - CJC Open
SN - 2589-790X
IS - 7
ER -