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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

      research-article
      1 , 4 , 10 , 11 , * , 1 , 10 , * , 12 , * , 10 , * , 1 , 10 , * , 1 , 1 , 10 , 1 , 10 , 1 , 10 , 10 , 11 , 10 , 1 , 10 , 1 , 10 , 2 , 5 , 6 , 4 , 10 , 10 , 1 , 10 , 13 , 14 , 15 , 5 , 7 , 16 , 17 , 19 , 20 , 22 , 23 , 24 , 25 , 19 , 20 , 1 , 10 , 8 , 9 , 26 , 21 , 3 , 18 , 5 , , 27 , , 28 , , 1 , 4 , 10 , 11 ,
      Circulation Research
      Lippincott Williams & Wilkins
      angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker, coronavirus, COVID-19, hypertension, inpatients

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          Abstract

          Supplemental Digital Content is available in the text.

          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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          Most cited references23

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          Clinical Characteristics of Coronavirus Disease 2019 in China

          Abstract Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)
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            Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

            Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.
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              Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China

              In December 2019, novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited.
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                Author and article information

                Journal
                Circ Res
                Circ. Res
                RES
                Circulation Research
                Lippincott Williams & Wilkins
                0009-7330
                1524-4571
                05 June 2020
                17 April 2020
                : 126
                : 12
                : 1671-1681
                Affiliations
                [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 ]Eye Center (X.Z.), Renmin Hospital of Wuhan University
                [3 ]Neonatology (B.-H.Z.), Renmin Hospital of Wuhan University
                [4 ]Medical Science Research Center (P.Z., Y.-X.J., H.L.), Zhongnan Hospital of Wuhan University
                [5 ]Hepatobiliary and Pancreatic Surgery (D.G., H.W., Y. Yuan), Zhongnan Hospital of Wuhan University
                [6 ]Cardiology (Y.P.), Zhongnan Hospital of Wuhan University
                [7 ]Gastroenterology (J.L.), Zhongnan Hospital of Wuhan University
                [8 ]Center for Evidence-Based and Translational Medicine (X.W.), Zhongnan Hospital of Wuhan University
                [9 ]Urology (X.W.), Zhongnan Hospital of Wuhan University
                [10 ]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.)
                [11 ]Basic Medical School, Wuhan University (P.Z., L. Lin, H.L.)
                [12 ]Cardiology, The Third Xiangya Hospital, Central South University, Changsha, China (J. Cai)
                [13 ]Anesthesiology, Cardiovascular Research Laboratories, David Geffen School of Medicine, University of California, Los Angeles (Y.W.)
                [14 ]Centre for Clinic Pharmacology, The William Harvey Research Institute, Queen Mary University of London, United Kingdom (Q.X.)
                [15 ]Wuhan Kanghuashuhai Technology Company (R.T.), Wuhan
                [16 ]Urology (P.L.), Wuhan Third Hospital & Tongren Hospital of Wuhan University
                [17 ]Intensive Care Unit (S.F.), Wuhan Third Hospital & Tongren Hospital of Wuhan University
                [18 ]Gastroenterology (X.H.), Wuhan Third Hospital & Tongren Hospital of Wuhan University
                [19 ]Wuhan Ninth Hospital (H.C., M.L.)
                [20 ]Cardiology, The Central Hospital of Wuhan (P.Y., M.C.)
                [21 ]Cardiovascular Surgery, Union Hospital (J.Xia), Tongji Medical College, Huazhong University of Science and Technology
                [22 ]Stomatology, Xiantao First People’s Hospital (B.X.)
                [23 ]General Surgery, Huanggang Central Hospital, Wuhan, China (W.M.)
                [24 ]General Surgery, Ezhou Central Hospital (L. Liu)
                [25 ]Infections Department, Wuhan Seventh Hospital (Y. Yan)
                [26 ]Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, United Kingdom (R.M.T.)
                [27 ]NAFLD Research Center, Division of Gastroenterology and Epidemiology, University of California San Diego, CA (L.R.)
                [28 ]Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ontario, Canada (P.P.L.).
                Author notes
                Correspondence to: Hongliang Li, MD, PhD, Cardiology, Renmin Hospital of Wuhan University, 99 Zhangzhidong Rd, Wuhan 430060, China, Email lihl@ 123456whu.edu.cn
                Peter P. Liu, MD, Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa, Ontario, Canada, Email pliu@ 123456ottawaheart.ca
                Loomba Rohit, MD, MHSc, Division of Gastroenterology and Epidemiology, University of California at San Diego, Email roloomba@ 123456health.ucsd.edu
                Yufeng Yuan, Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Email yuanyf1971@ 123456whu.edu.cn
                Article
                00003
                10.1161/CIRCRESAHA.120.317134
                7265882
                32302265
                a9ad6e0e-c9ba-4fbc-b96f-957dfc1aa089
                © 2020 The Authors.

                Circulation Research is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited.

                This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.

                History
                : 13 April 2020
                : 17 April 2020
                : 17 April 2020
                Categories
                10010
                Original Research
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                angiotensin-converting enzyme inhibitor,angiotensin ii receptor blocker,coronavirus,covid-19,hypertension,inpatients

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