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Association of Inpatient Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Mortality Among Patients With Hypertension Hospitalized With COVID-19.
Circ Res. 2020 06 05; 126(12):1671-1681.CircR

Abstract

RATIONALE

Use of ACEIs (angiotensin-converting enzyme inhibitors) and ARBs (angiotensin II receptor blockers) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in patients with hypertension.

OBJECTIVE

To determine the association between in-hospital use of ACEI/ARB and all-cause mortality in patients with hypertension and hospitalized due to COVID-19.

METHODS AND RESULTS

This retrospective, multi-center study included 1128 adult patients with hypertension diagnosed with COVID-19, including 188 taking ACEI/ARB (ACEI/ARB group; median age 64 [interquartile range, 55-68] years; 53.2% men) and 940 without using ACEI/ARB (non-ACEI/ARB group; median age 64 [interquartile range 57-69]; 53.5% men), who were admitted to 9 hospitals in Hubei Province, China from December 31, 2019 to February 20, 2020. In mixed-effect Cox model treating site as a random effect, after adjusting for age, gender, comorbidities, and in-hospital medications, the detected risk for all-cause mortality was lower in the ACEI/ARB group versus the non-ACEI/ARB group (adjusted hazard ratio, 0.42 [95% CI, 0.19-0.92]; P=0.03). In a propensity score-matched analysis followed by adjusting imbalanced variables in mixed-effect Cox model, the results consistently demonstrated lower risk of COVID-19 mortality in patients who received ACEI/ARB versus those who did not receive ACEI/ARB (adjusted hazard ratio, 0.37 [95% CI, 0.15-0.89]; P=0.03). Further subgroup propensity score-matched analysis indicated that, compared with use of other antihypertensive drugs, ACEI/ARB was also associated with decreased mortality (adjusted hazard ratio, 0.30 [95% CI, 0.12-0.70]; P=0.01) in patients with COVID-19 and coexisting hypertension.

CONCLUSIONS

Among hospitalized patients with COVID-19 and coexisting hypertension, inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB nonusers. While study interpretation needs to consider the potential for residual confounders, it is unlikely that in-hospital use of ACEI/ARB was associated with an increased mortality risk.

Authors+Show Affiliations

From the Cardiology (P.Z., L.Z., J.-J.Q., J. Xie, Y.-M.L., Y.-C.Z., X. Huang, M.-M.C., X.C., Z.-G.S., X.-J.Z., H.L.), Renmin Hospital of Wuhan University. Medical Science Research Center (P.Z., Y.-X.J., H.L.), Zhongnan Hospital of Wuhan University. Institute of Model Animal of Wuhan University (P.Z., L.Z., F.L., J.-J.Q., Y.-M.L., Y.-C.Z., X. Huang, L. Lin, M.X., M.-M.C., X.C., Y.-X.J., J. Chen, Z.-G.S., X.-J.Z., H.L.). Basic Medical School, Wuhan University (P.Z., L. Lin, H.L.).From the Cardiology (P.Z., L.Z., J.-J.Q., J. Xie, Y.-M.L., Y.-C.Z., X. Huang, M.-M.C., X.C., Z.-G.S., X.-J.Z., H.L.), Renmin Hospital of Wuhan University. Institute of Model Animal of Wuhan University (P.Z., L.Z., F.L., J.-J.Q., Y.-M.L., Y.-C.Z., X. Huang, L. Lin, M.X., M.-M.C., X.C., Y.-X.J., J. Chen, Z.-G.S., X.-J.Z., H.L.).Cardiology, The Third Xiangya Hospital, Central South University, Changsha, China (J. Cai).Institute of Model Animal of Wuhan University (P.Z., L.Z., F.L., J.-J.Q., Y.-M.L., Y.-C.Z., X. Huang, L. Lin, M.X., M.-M.C., X.C., Y.-X.J., J. Chen, Z.-G.S., X.-J.Z., H.L.).From the Cardiology (P.Z., L.Z., J.-J.Q., J. Xie, Y.-M.L., Y.-C.Z., X. Huang, M.-M.C., X.C., Z.-G.S., X.-J.Z., H.L.), Renmin Hospital of Wuhan University. Institute of Model Animal of Wuhan University (P.Z., L.Z., F.L., J.-J.Q., Y.-M.L., Y.-C.Z., X. Huang, L. Lin, M.X., M.-M.C., X.C., Y.-X.J., J. Chen, Z.-G.S., X.-J.Z., H.L.).From the Cardiology (P.Z., L.Z., J.-J.Q., J. Xie, Y.-M.L., Y.-C.Z., X. Huang, M.-M.C., X.C., Z.-G.S., X.-J.Z., H.L.), Renmin Hospital of Wuhan University.From the Cardiology (P.Z., L.Z., J.-J.Q., J. Xie, Y.-M.L., Y.-C.Z., X. Huang, M.-M.C., X.C., Z.-G.S., X.-J.Z., H.L.), Renmin Hospital of Wuhan University. Institute of Model Animal of Wuhan University (P.Z., L.Z., F.L., J.-J.Q., Y.-M.L., Y.-C.Z., X. Huang, L. Lin, M.X., M.-M.C., X.C., Y.-X.J., J. Chen, Z.-G.S., X.-J.Z., H.L.).From the Cardiology (P.Z., L.Z., J.-J.Q., J. Xie, Y.-M.L., Y.-C.Z., X. Huang, M.-M.C., X.C., Z.-G.S., X.-J.Z., H.L.), Renmin Hospital of Wuhan University. Institute of Model Animal of Wuhan University (P.Z., L.Z., F.L., J.-J.Q., Y.-M.L., Y.-C.Z., X. Huang, L. Lin, M.X., M.-M.C., X.C., Y.-X.J., J. Chen, Z.-G.S., X.-J.Z., H.L.).From the Cardiology (P.Z., L.Z., J.-J.Q., J. Xie, Y.-M.L., Y.-C.Z., X. Huang, M.-M.C., X.C., Z.-G.S., X.-J.Z., H.L.), Renmin Hospital of Wuhan University. Institute of Model Animal of Wuhan University (P.Z., L.Z., F.L., J.-J.Q., Y.-M.L., Y.-C.Z., X. Huang, L. Lin, M.X., M.-M.C., X.C., Y.-X.J., J. Chen, Z.-G.S., X.-J.Z., H.L.).Institute of Model Animal of Wuhan University (P.Z., L.Z., F.L., J.-J.Q., Y.-M.L., Y.-C.Z., X. Huang, L. Lin, M.X., M.-M.C., X.C., Y.-X.J., J. Chen, Z.-G.S., X.-J.Z., H.L.). Basic Medical School, Wuhan University (P.Z., L. Lin, H.L.).Institute of Model Animal of Wuhan University (P.Z., L.Z., F.L., J.-J.Q., Y.-M.L., Y.-C.Z., X. Huang, L. Lin, M.X., M.-M.C., X.C., Y.-X.J., J. Chen, Z.-G.S., X.-J.Z., H.L.).From the Cardiology (P.Z., L.Z., J.-J.Q., J. Xie, Y.-M.L., Y.-C.Z., X. Huang, M.-M.C., X.C., Z.-G.S., X.-J.Z., H.L.), Renmin Hospital of Wuhan University. Institute of Model Animal of Wuhan University (P.Z., L.Z., F.L., J.-J.Q., Y.-M.L., Y.-C.Z., X. Huang, L. Lin, M.X., M.-M.C., X.C., Y.-X.J., J. Chen, Z.-G.S., X.-J.Z., H.L.).From the Cardiology (P.Z., L.Z., J.-J.Q., J. Xie, Y.-M.L., Y.-C.Z., X. Huang, M.-M.C., X.C., Z.-G.S., X.-J.Z., H.L.), Renmin Hospital of Wuhan University. Institute of Model Animal of Wuhan University (P.Z., L.Z., F.L., J.-J.Q., Y.-M.L., Y.-C.Z., X. Huang, L. Lin, M.X., M.-M.C., X.C., Y.-X.J., J. Chen, Z.-G.S., X.-J.Z., H.L.).Eye Center (X.Z.), Renmin Hospital of Wuhan University.Hepatobiliary and Pancreatic Surgery (D.G., H.W., Y. Yuan), Zhongnan Hospital of Wuhan University.Cardiology (Y.P.), Zhongnan Hospital of Wuhan University.Medical Science Research Center (P.Z., Y.-X.J., H.L.), Zhongnan Hospital of Wuhan University. Institute of Model Animal of Wuhan University (P.Z., L.Z., F.L., J.-J.Q., Y.-M.L., Y.-C.Z., X. Huang, L. Lin, M.X., M.-M.C., X.C., Y.-X.J., J. Chen, Z.-G.S., X.-J.Z., H.L.).Institute of Model Animal of Wuhan University (P.Z., L.Z., F.L., J.-J.Q., Y.-M.L., Y.-C.Z., X. Huang, L. Lin, M.X., M.-M.C., X.C., Y.-X.J., J. Chen, Z.-G.S., X.-J.Z., H.L.).From the Cardiology (P.Z., L.Z., J.-J.Q., J. Xie, Y.-M.L., Y.-C.Z., X. Huang, M.-M.C., X.C., Z.-G.S., X.-J.Z., H.L.), Renmin Hospital of Wuhan University. Institute of Model Animal of Wuhan University (P.Z., L.Z., F.L., J.-J.Q., Y.-M.L., Y.-C.Z., X. Huang, L. Lin, M.X., M.-M.C., X.C., Y.-X.J., J. Chen, Z.-G.S., X.-J.Z., H.L.).Anesthesiology, Cardiovascular Research Laboratories, David Geffen School of Medicine, University of California, Los Angeles (Y.W.).Centre for Clinic Pharmacology, The William Harvey Research Institute, Queen Mary University of London, United Kingdom (Q.X.).Wuhan Kanghuashuhai Technology Company (R.T.), Wuhan.Hepatobiliary and Pancreatic Surgery (D.G., H.W., Y. Yuan), Zhongnan Hospital of Wuhan University.Gastroenterology (J.L.), Zhongnan Hospital of Wuhan University.Urology (P.L.), Wuhan Third Hospital & Tongren Hospital of Wuhan University.Intensive Care Unit (S.F.), Wuhan Third Hospital & Tongren Hospital of Wuhan University.Wuhan Ninth Hospital (H.C., M.L.).Cardiology, The Central Hospital of Wuhan (P.Y., M.C.).Stomatology, Xiantao First People's Hospital (B.X.).General Surgery, Huanggang Central Hospital, Wuhan, China (W.M.).General Surgery, Ezhou Central Hospital (L. Liu).Infections Department, Wuhan Seventh Hospital (Y. Yan).Wuhan Ninth Hospital (H.C., M.L.).Cardiology, The Central Hospital of Wuhan (P.Y., M.C.).From the Cardiology (P.Z., L.Z., J.-J.Q., J. Xie, Y.-M.L., Y.-C.Z., X. Huang, M.-M.C., X.C., Z.-G.S., X.-J.Z., H.L.), Renmin Hospital of Wuhan University. Institute of Model Animal of Wuhan University (P.Z., L.Z., F.L., J.-J.Q., Y.-M.L., Y.-C.Z., X. Huang, L. Lin, M.X., M.-M.C., X.C., Y.-X.J., J. Chen, Z.-G.S., X.-J.Z., H.L.).Center for Evidence-Based and Translational Medicine (X.W.), Zhongnan Hospital of Wuhan University. Urology (X.W.), Zhongnan Hospital of Wuhan University.Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, United Kingdom (R.M.T.).Cardiovascular Surgery, Union Hospital (J.Xia), Tongji Medical College, Huazhong University of Science and Technology.Neonatology (B.-H.Z.), Renmin Hospital of Wuhan University.Gastroenterology (X.H.), Wuhan Third Hospital & Tongren Hospital of Wuhan University.Hepatobiliary and Pancreatic Surgery (D.G., H.W., Y. Yuan), Zhongnan Hospital of Wuhan University.NAFLD Research Center, Division of Gastroenterology and Epidemiology, University of California San Diego, CA (L.R.).Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ontario, Canada (P.P.L.).From the Cardiology (P.Z., L.Z., J.-J.Q., J. Xie, Y.-M.L., Y.-C.Z., X. Huang, M.-M.C., X.C., Z.-G.S., X.-J.Z., H.L.), Renmin Hospital of Wuhan University. Medical Science Research Center (P.Z., Y.-X.J., H.L.), Zhongnan Hospital of Wuhan University. Institute of Model Animal of Wuhan University (P.Z., L.Z., F.L., J.-J.Q., Y.-M.L., Y.-C.Z., X. Huang, L. Lin, M.X., M.-M.C., X.C., Y.-X.J., J. Chen, Z.-G.S., X.-J.Z., H.L.). Basic Medical School, Wuhan University (P.Z., L. Lin, H.L.).

Pub Type(s)

Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32302265

Citation

Zhang, Peng, et al. "Association of Inpatient Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Mortality Among Patients With Hypertension Hospitalized With COVID-19." Circulation Research, vol. 126, no. 12, 2020, pp. 1671-1681.
Zhang P, Zhu L, Cai J, et al. Association of Inpatient Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Mortality Among Patients With Hypertension Hospitalized With COVID-19. Circ Res. 2020;126(12):1671-1681.
Zhang, P., Zhu, L., Cai, J., Lei, F., Qin, J. J., Xie, J., Liu, Y. M., Zhao, Y. C., Huang, X., Lin, L., Xia, M., Chen, M. M., Cheng, X., Zhang, X., Guo, D., Peng, Y., Ji, Y. X., Chen, J., She, Z. G., ... Li, H. (2020). Association of Inpatient Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Mortality Among Patients With Hypertension Hospitalized With COVID-19. Circulation Research, 126(12), 1671-1681. https://doi.org/10.1161/CIRCRESAHA.120.317134
Zhang P, et al. Association of Inpatient Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Mortality Among Patients With Hypertension Hospitalized With COVID-19. Circ Res. 2020 06 5;126(12):1671-1681. PubMed PMID: 32302265.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of Inpatient Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Mortality Among Patients With Hypertension Hospitalized With COVID-19. AU - Zhang,Peng, AU - Zhu,Lihua, AU - Cai,Jingjing, AU - Lei,Fang, AU - Qin,Juan-Juan, AU - Xie,Jing, AU - Liu,Ye-Mao, AU - Zhao,Yan-Ci, AU - Huang,Xuewei, AU - Lin,Lijin, AU - Xia,Meng, AU - Chen,Ming-Ming, AU - Cheng,Xu, AU - Zhang,Xiao, AU - Guo,Deliang, AU - Peng,Yuanyuan, AU - Ji,Yan-Xiao, AU - Chen,Jing, AU - She,Zhi-Gang, AU - Wang,Yibin, AU - Xu,Qingbo, AU - Tan,Renfu, AU - Wang,Haitao, AU - Lin,Jun, AU - Luo,Pengcheng, AU - Fu,Shouzhi, AU - Cai,Hongbin, AU - Ye,Ping, AU - Xiao,Bing, AU - Mao,Weiming, AU - Liu,Liming, AU - Yan,Youqin, AU - Liu,Mingyu, AU - Chen,Manhua, AU - Zhang,Xiao-Jing, AU - Wang,Xinghuan, AU - Touyz,Rhian M, AU - Xia,Jiahong, AU - Zhang,Bing-Hong, AU - Huang,Xiaodong, AU - Yuan,Yufeng, AU - Rohit,Loomba, AU - Liu,Peter P, AU - Li,Hongliang, Y1 - 2020/04/17/ PY - 2020/4/18/pubmed PY - 2020/6/19/medline PY - 2020/4/18/entrez KW - COVID-19 KW - angiotensin II receptor blocker KW - angiotensin-converting enzyme inhibitor KW - coronavirus KW - hypertension KW - inpatients SP - 1671 EP - 1681 JF - Circulation research JO - Circ. Res. VL - 126 IS - 12 N2 - RATIONALE: Use of ACEIs (angiotensin-converting enzyme inhibitors) and ARBs (angiotensin II receptor blockers) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in patients with hypertension. OBJECTIVE: To determine the association between in-hospital use of ACEI/ARB and all-cause mortality in patients with hypertension and hospitalized due to COVID-19. METHODS AND RESULTS: This retrospective, multi-center study included 1128 adult patients with hypertension diagnosed with COVID-19, including 188 taking ACEI/ARB (ACEI/ARB group; median age 64 [interquartile range, 55-68] years; 53.2% men) and 940 without using ACEI/ARB (non-ACEI/ARB group; median age 64 [interquartile range 57-69]; 53.5% men), who were admitted to 9 hospitals in Hubei Province, China from December 31, 2019 to February 20, 2020. In mixed-effect Cox model treating site as a random effect, after adjusting for age, gender, comorbidities, and in-hospital medications, the detected risk for all-cause mortality was lower in the ACEI/ARB group versus the non-ACEI/ARB group (adjusted hazard ratio, 0.42 [95% CI, 0.19-0.92]; P=0.03). In a propensity score-matched analysis followed by adjusting imbalanced variables in mixed-effect Cox model, the results consistently demonstrated lower risk of COVID-19 mortality in patients who received ACEI/ARB versus those who did not receive ACEI/ARB (adjusted hazard ratio, 0.37 [95% CI, 0.15-0.89]; P=0.03). Further subgroup propensity score-matched analysis indicated that, compared with use of other antihypertensive drugs, ACEI/ARB was also associated with decreased mortality (adjusted hazard ratio, 0.30 [95% CI, 0.12-0.70]; P=0.01) in patients with COVID-19 and coexisting hypertension. CONCLUSIONS: Among hospitalized patients with COVID-19 and coexisting hypertension, inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB nonusers. While study interpretation needs to consider the potential for residual confounders, it is unlikely that in-hospital use of ACEI/ARB was associated with an increased mortality risk. SN - 1524-4571 UR - https://www.unboundmedicine.com/medline/citation/32302265/full_citation L2 - http://www.ahajournals.org/doi/full/10.1161/CIRCRESAHA.120.317134?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -