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Cited by 1,133COVID-19 Clinical Research StudiesRenin-Angiotensin System StudiesCOVID-19 and healthcare impacts

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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

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Zhang, Peng, Zhu, Lihua, Cai, Jingjing, Lei, Fang, Qin, Juan-Juan, Xie, Jing, Liu, Ye-Mao, Zhao, Yan-Ci, Huang, Xuewei, Lin, Lijin, Xia, Meng, Chen, Ming-Ming, Cheng, Xu, Zhang, Xiao, Guo, Deliang, Peng, Yuanyuan, Ji, Yan-Xiao, Chen, Jing, She, Zhi-Gang, Wang, Yibin, Xu, Qingbo, Tan, Renfu, Wang, Haitao, Lin, Jun, Luo, Pengcheng, Fu, Shouzhi, Cai, Hongbin, Ye, Ping, Xiao, Bing, Mao, Weiming, Liu, Liming, Yan, Youqin, Liu, Mingyu, Chen, Manhua, Zhang, Xiao-Jing, Wang, Xinghuan, Touyz, Rhian M., Xia, Jiahong, Zhang, Bing-Hong, Huang, Xiaodong, Yuan, Yufeng, Loomba, Rohit, Liu, Peter P., Li, Hongliang·2020·Circulation Research
DOI 10.1161/circresaha.120.317134PMC PMC7265882
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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.

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Figure 1. The flowchart showing the strategy of participant enrollment. a, 1128 participants with a history of hypertension enrolled in the hypertension cohort. b, 2302 participants without a history of hypertension enrolled in the nonhypertension cohort. c, 188 patients with hypertension who taking ACEI (angiotensin-converting enzyme inhibitor) or ARB (angiotensin II receptor blocker) during hospitalization were enrolled in the ACEI/ARB cohort. Patients discontinued treatment of hypertension due to inability to take medications or hypotension were not excluded from the cohort. d, 940 patients with hypertension who never taking ACEI and ARB during hospitalization were enrolled in the non-ACEI/ARB cohort. e, Propensity score-matched age, gender, cough, dyspnea, comorbidities (diabetes mellitus, coronary heart disease, and chronic renal disease), chest computerized tomography (CT)-diagnosed lung lesions, and incidence of increased CRP (C-reactive protein) and creatine. Hospital site as a random effect in the mixed-effect Cox model. f, 557 patients with antihypertension drug who never taking ACEI and ARB during hospitalization were enrolled in the secondary non-ACEI/ARB cohort. SARS-COV-2 indicates severe acute respiratory syndrome coronavirus 2.
Figure 1. The flowchart showing the strategy of participant enrollment. a, 1128 participants with a history of hypertension enrolled in the hypertension cohort. b, 2302 participants without a history of hypertension enrolled in the nonhypertension cohort. c, 188 patients with hypertension who taking ACEI (angiotensin-converting enzyme inhibitor) or ARB (angiotensin II receptor blocker) during hospitalization were enrolled in the ACEI/ARB cohort. Patients discontinued treatment of hypertension due to inability to take medications or hypotension were not excluded from the cohort. d, 940 patients with hypertension who never taking ACEI and ARB during hospitalization were enrolled in the non-ACEI/ARB cohort. e, Propensity score-matched age, gender, cough, dyspnea, comorbidities (diabetes mellitus, coronary heart disease, and chronic renal disease), chest computerized tomography (CT)-diagnosed lung lesions, and incidence of increased CRP (C-reactive protein) and creatine. Hospital site as a random effect in the mixed-effect Cox model. f, 557 patients with antihypertension drug who never taking ACEI and ARB during hospitalization were enrolled in the secondary non-ACEI/ARB cohort. SARS-COV-2 indicates severe acute respiratory syndrome coronavirus 2.CC BY · PubMed Central
Figure 2. Kaplan-Meier curves for cumulative probability of Coronavirus disease 2019 (COVID-19) mortality during 28-day follow-up duration in ACEI (angiotensin-converting enzyme inhibitor)/ARB (angiotensin II receptor blocker) or non-ACEI/ARB cohort among 1128 patients with hypertension. The unmatched model and the median (interquartile range [IQR]) observation time was 28 (20–28) in ACEI/ARB cohort and 28 (19–28) in non-ACEI/ARB cohort (A). Propensity-score matched model and the median (IQR) observation time was 28 (20.5–28) in ACEI/ARB cohort and 28 (18–28) in non-ACEI/ARB cohort (B). The blips indicate censoring. HR indicates hazard ratio.
Figure 2. Kaplan-Meier curves for cumulative probability of Coronavirus disease 2019 (COVID-19) mortality during 28-day follow-up duration in ACEI (angiotensin-converting enzyme inhibitor)/ARB (angiotensin II receptor blocker) or non-ACEI/ARB cohort among 1128 patients with hypertension. The unmatched model and the median (interquartile range [IQR]) observation time was 28 (20–28) in ACEI/ARB cohort and 28 (19–28) in non-ACEI/ARB cohort (A). Propensity-score matched model and the median (IQR) observation time was 28 (20.5–28) in ACEI/ARB cohort and 28 (18–28) in non-ACEI/ARB cohort (B). The blips indicate censoring. HR indicates hazard ratio.CC BY · PubMed Central

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Authors
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., Wang, Y., Xu, Q., Tan, R., Wang, H., Lin, J., Luo, P., Fu, S., Cai, H., Ye, P., Xiao, B., Mao, W., Liu, L., Yan, Y., Liu, M., Chen, M., Zhang, X.-J., Wang, X., Touyz, R. M., Xia, J., Zhang, B.-H., Huang, X., Yuan, Y., Loomba, R., Liu, P. P., & Li, H.
Affiliations
  • Wuhan University (CN)
  • Central South University (CN)
  • Renmin Hospital of Wuhan University (CN)
  • 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
  • Zhongnan Hospital of Wuhan University (CN)
  • University of California, Los Angeles (US)
  • Queen Mary University of London (GB)
  • Wuhan Kanghuashuhai Technology Company (R.T.), Wuhan
  • Wuhan Ninth Hospital (H.C., M.L.)
  • Central Hospital of Wuhan (CN)
  • Stomatology, Xiantao First People’s Hospital (B.X.)
  • Huanggang Central Hospital (CN)
  • Ezhou Central Hospital (CN)
  • Wuhan No. 7 Hospital (CN)
  • University of Glasgow (GB)
  • Huazhong University of Science and Technology (CN)
  • Neonatology (B.-H.Z.), Renmin Hospital of Wuhan University
  • University of California San Diego (US)
  • Ottawa Heart Institute (CA)
Corresponding author
  • Zhang, Peng
  • Zhu, Lihua
  • Cai, Jingjing
  • Lei, Fang
  • Qin, Juan-Juan
ORCID
Venue
Circulation Research
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2020-06-05
Volume
126
Issue
12
Pages
1671-1681
ISSN
  • 0009-7330 (ISSN-L)
  • 1524-4571
DOI
10.1161/circresaha.120.317134
PMC
PMC7265882
OpenAlex
W3016572296
Cited by
1,133
References
32
Citations by year
2026: 6 · 2025: 16 · 2024: 47 · 2023: 81 · 2022: 120 · 2021: 324 · 2020: 537
FWCI
34.87
Type
journal article
Language
en
Update notices
correction (2020-08-27)
Open access
Licence
cc-by
Locations
  • Circulation Research (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders
  • National Key R&D program of China (2016YFF0101504, 2020YFC0845500)
  • National Science Foundation of China (81630011; 81970364;81970070;81970011;81870171; 81700356)
  • Major Research Plan of the National Natural Science Foundation of China (91639304)
  • Hubei Science and Technology Support Project (2019BFC582; 2018BEC473; 2017BEC001)
  • Medical flight plan of Wuhan University
Topics
  • Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
  • Health Sciences › Medicine › Oncology › COVID-19 and healthcare impacts
Keywords
COVID-19 pandemic, hypertension, ACE inhibitors, angiotensin receptor blockers, all-cause mortality, antihypertensive drugs, hospitalized patients, SARS-CoV-2, 2020 outbreak, propensity score matching
MeSH terms
COVID-19, Aged, Angiotensin-Converting Enzyme Inhibitors, Female, Humans, Hypertension, Inpatients, Male, Middle Aged, Pneumonia, Viral, Hospital Mortality, Coronavirus Infections, Angiotensin Receptor Antagonists, Pandemics

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