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      Continued In-Hospital Angiotensin-Converting Enzyme Inhibitor and Angiotensin II Receptor Blocker Use in Hypertensive COVID-19 Patients Is Associated With Positive Clinical Outcome

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          Abstract

          Background

          This study investigated continued and discontinued use of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB) during hospitalization of 614 hypertensive laboratory-confirmed COVID-19 patients.

          Methods

          Demographics, comorbidities, vital signs, laboratory data, and ACEi/ARB usage were analyzed. To account for confounders, patients were substratified by whether they developed hypotension and acute kidney injury (AKI) during the index hospitalization.

          Results

          Mortality (22% vs 17%, P > .05) and intensive care unit (ICU) admission (26% vs 12%, P > .05) rates were not significantly different between non-ACEi/ARB and ACEi/ARB groups. However, patients who continued ACEi/ARBs in the hospital had a markedly lower ICU admission rate (12% vs 26%; P = .001; odds ratio [OR] = 0.347; 95% confidence interval [CI], .187–.643) and mortality rate (6% vs 28%; P = .001; OR = 0.215; 95% CI, .101–.455) compared to patients who discontinued ACEi/ARB. The odds ratio for mortality remained significantly lower after accounting for development of hypotension or AKI.

          Conclusions

          These findings suggest that continued ACEi/ARB use in hypertensive COVID-19 patients yields better clinical outcomes.

          Abstract

          In hypertensive patients with COVID-19, in-hospital continuation of ACE inhibitors or ARBs is associated with lower rates of mortality and intensive care admission in the absence of hypotension or acute kidney injury.

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          Most cited references 14

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          Renin-Angiotensin System Blockers and the COVID-19 Pandemic

          During the spread of the severe acute respiratory syndrome coronavirus-2, some reports of data still emerging and in need of full analysis indicate that certain groups of patients are at risk of COVID-19. This includes patients with hypertension, heart disease, diabetes mellitus, and clearly the elderly. Many of those patients are treated with renin-angiotensin system blockers. Because the ACE2 (angiotensin-converting enzyme 2) protein is the receptor that facilitates coronavirus entry into cells, the notion has been popularized that treatment with renin-angiotensin system blockers might increase the risk of developing a severe and fatal severe acute respiratory syndrome coronavirus-2 infection. The present article discusses this concept. ACE2 in its full-length form is a membrane-bound enzyme, whereas its shorter (soluble) form circulates in blood at very low levels. As a mono-carboxypeptidase, ACE2 contributes to the degradation of several substrates including angiotensins I and II. ACE (angiotensin-converting enzyme) inhibitors do not inhibit ACE2 because ACE and ACE2 are different enzymes. Although angiotensin II type 1 receptor blockers have been shown to upregulate ACE2 in experimental animals, the evidence is not always consistent and differs among the diverse angiotensin II type 1 receptor blockers and differing organs. Moreover, there are no data to support the notion that ACE inhibitor or angiotensin II type 1 receptor blocker administration facilitates coronavirus entry by increasing ACE2 expression in either animals or humans. Indeed, animal data support elevated ACE2 expression as conferring potential protective pulmonary and cardiovascular effects. In summary, based on the currently available evidence, treatment with renin-angiotensin system blockers should not be discontinued because of concerns with coronavirus infection.
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            Long-term ACE-inhibitor therapy in patients with heart failure or left-ventricular dysfunction: a systematic overview of data from individual patients. ACE-Inhibitor Myocardial Infarction Collaborative Group.

            We undertook a prospective systematic overview based on data from individual patients from five long-term randomised trials that assessed inhibitors of angiotensin-converting enzyme (ACE) in patients with left-ventricular dysfunction or heart failure. Three of the trials enrolled patients within a week after acute myocardial infarction. Data were combined by use of the Peto-Yusuf method. Overall 12,763 patients were randomly assigned treatment or placebo and followed up for an average of 35 months. In the three post-infarction trials (n=5,966), mortality was lower with ACE inhibitors than with placebo (702/2995 [23.4%] vs 866/2971 [29.1%]; odds ratio 0.74 [95% CI 0.66-0-83]), as were the rates of readmission for heart failure (355 [11.9%] vs 460 [15.5%]; 0.73 [0.63-0.85]), reinfarction (324 [10.8%] vs 391 [13.2%]; 0.80 [0.69-0.94]), or the composite of these events (1049 [35.0%] vs 1244 [41.9%]; 0.75 [0.67-0.83]; all p
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              Long-term ACE-inhibitor therapy in patients with heart failure or left-ventricular dysfunction: a systematic overview of data from individual patients

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                Author and article information

                Journal
                J Infect Dis
                J. Infect. Dis
                jid
                The Journal of Infectious Diseases
                Oxford University Press (US )
                0022-1899
                1537-6613
                23 July 2020
                Affiliations
                [1 ] Department of Radiology, Renaissance School of Medicine, Stony Brook University , New York, New York, USA
                [2 ] Department of Medicine, Renaissance School of Medicine, Stony Brook University , New York, New York, USA
                [3 ] Department of Emergency Medicine, Renaissance School of Medicine, Stony Brook University , New York, New York, USA
                Author notes
                Correspondence: Tim Duong, PhD, Radiology, Renaissance School of Medicine, Stony Brook University, New York, NY 11794 ( tim.duong@ 123456stonybrook.edu ).

                K. W. L. and K. W. C contributed equally.

                Article
                jiaa447
                10.1093/infdis/jiaa447
                7454718
                32702098
                © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

                This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model ( https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

                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.

                Page count
                Pages: 9
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                AcademicSubjects/MED00860
                AcademicSubjects/MED00290
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