Association of Inpatient Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Mortality Among Patients With Hypertension Hospitalized With COVID-19

Author:

Zhang Peng1234,Zhu Lihua13,Cai Jingjing5,Lei Fang3,Qin Juan-Juan13,Xie Jing1,Liu Ye-Mao13,Zhao Yan-Ci13,Huang Xuewei13,Lin Lijin34,Xia Meng3,Chen Ming-Ming13,Cheng Xu13,Zhang Xiao6,Guo Deliang7,Peng Yuanyuan8,Ji Yan-Xiao23,Chen Jing3,She Zhi-Gang13,Wang Yibin9,Xu Qingbo10,Tan Renfu11,Wang Haitao7,Lin Jun12,Luo Pengcheng13,Fu Shouzhi14,Cai Hongbin15,Ye Ping16,Xiao Bing17,Mao Weiming18,Liu Liming19,Yan Youqin20,Liu Mingyu15,Chen Manhua16,Zhang Xiao-Jing13,Wang Xinghuan2122,Touyz Rhian M.23,Xia Jiahong24,Zhang Bing-Hong25,Huang Xiaodong26,Yuan Yufeng7,Loomba Rohit27,Liu Peter P.28,Li Hongliang1234ORCID

Affiliation:

1. 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

2. Medical Science Research Center (P.Z., Y.-X.J., H.L.), Zhongnan Hospital of Wuhan University

3. 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.)

4. Basic Medical School, Wuhan University (P.Z., L. Lin, H.L.)

5. Cardiology, The Third Xiangya Hospital, Central South University, Changsha, China (J. Cai)

6. Eye Center (X.Z.), Renmin Hospital of Wuhan University

7. Hepatobiliary and Pancreatic Surgery (D.G., H.W., Y. Yuan), Zhongnan Hospital of Wuhan University

8. Cardiology (Y.P.), Zhongnan Hospital of Wuhan University

9. Anesthesiology, Cardiovascular Research Laboratories, David Geffen School of Medicine, University of California, Los Angeles (Y.W.)

10. Centre for Clinic Pharmacology, The William Harvey Research Institute, Queen Mary University of London, United Kingdom (Q.X.)

11. Wuhan Kanghuashuhai Technology Company (R.T.), Wuhan

12. Gastroenterology (J.L.), Zhongnan Hospital of Wuhan University

13. Urology (P.L.), Wuhan Third Hospital & Tongren Hospital of Wuhan University

14. Intensive Care Unit (S.F.), Wuhan Third Hospital & Tongren Hospital of Wuhan University

15. Wuhan Ninth Hospital (H.C., M.L.)

16. Cardiology, The Central Hospital of Wuhan (P.Y., M.C.)

17. Stomatology, Xiantao First People’s Hospital (B.X.)

18. General Surgery, Huanggang Central Hospital, Wuhan, China (W.M.)

19. General Surgery, Ezhou Central Hospital (L. Liu)

20. Infections Department, Wuhan Seventh Hospital (Y. Yan)

21. Center for Evidence-Based and Translational Medicine (X.W.), Zhongnan Hospital of Wuhan University

22. Urology (X.W.), Zhongnan Hospital of Wuhan University

23. Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, United Kingdom (R.M.T.)

24. Cardiovascular Surgery, Union Hospital (J.Xia), Tongji Medical College, Huazhong University of Science and Technology

25. Neonatology (B.-H.Z.), Renmin Hospital of Wuhan University

26. Gastroenterology (X.H.), Wuhan Third Hospital & Tongren Hospital of Wuhan University

27. NAFLD Research Center, Division of Gastroenterology and Epidemiology, University of California San Diego, CA (R.L.)

28. Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ontario, Canada (P.P.L.).

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.

Funder

National Key R&D program of China

National Science Foundation of China

Major Research Plan of the National Natural Science Foundation of China

Hubei Science and Technology Support Project

Medical flight plan of Wuhan University

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Cardiology and Cardiovascular Medicine,Physiology

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