COVID-19 and Angiotensin-Converting Enzyme Inhibitor/Angiotensin-Receptor Blocker Therapy
Authors: William G. Kussmaul
Journal: Annals of Internal Medicine (2020)

Editorials15 May 2020COVID-19 and Angiotensin-Converting Enzyme Inhibitor/Angiotensin-Receptor Blocker TherapyFREEWilliam G. Kussmaul III, MDWilliam G. Kussmaul III, MDMedia, Pennsylvania (W.G.K.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/M20-3047 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Coronavirus disease 2019 (COVID-19)–related concerns about angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) seem to have developed approximately as follows:•The epidemic broke out widely in January and February.•Early reports showed that common comorbid conditions, including hypertension, were statistically linked to worse illness severity.•Many hypertensive persons take ACEIs or ARBs.•Previous studies of a related coronavirus, the causal agent of the 2003–2004 severe acute respiratory syndrome epidemic, had shown that the ACE-2 membrane receptor is key to the ability of the virus to infect cells.•Both ACEIs and ARBs may upregulate the ACE-2 receptor.A cogent line of reasoning (1) therefore led to the following question (2): Could these drugs be magnifying the risk for COVID-19 or contributing to its severity?We now have abundant data from Italy, China, the United Kingdom, and the United States to suggest otherwise. These reports are summarized in a systematic review by Mackey and colleagues (3). The authors present data from 3 studies that found, with moderate certainty of evidence, no relationship of ACEI or ARB use with testing positive for the virus or becoming ill from it. On the basis of further data from 14 observational studies encompassing more than 23 000 adults with COVID-19, they found high-certainty evidence that the drugs are not associated with greater illness severity.In addition, common sense tells us that common comorbid conditions, such as hypertension and cardiovascular disease, are likely to be common in any population assessment. And it is a clinical truism that people with any chronic condition are more ill than those without. In the hallway vernacular, “What's common is common” and “The sicker you are, the sicker you are.” Initial fears that hypertension or its therapy uniquely contribute to COVID-19 illness seem now to have been unfounded.As a result of this progression from fear and theory through data and multiple analyses from different continents, we now have reasonable reassurance that drugs that alter the renin–angiotensin system (RAS) do not pose substantial threats as either COVID-19 risk factors or severity multipliers. And although there were reasons that RAS-related drugs might have been harmful, there are other reasons that they could be helpful (4). Furthermore, withdrawing these drugs if they are prescribed for evidence-based indications could harm patients, especially those with heart failure (5).At this time, professional societies and expert editorialists agree: Until further data show otherwise, these drugs should continue to be used for their standard indications (6). One might also add that there are currently insufficient outcomes data to show that they provide specific benefit during COVID-19 illness.Mackey and colleagues' review is one of a new class of “living systematic reviews.” The conclusions reached on the basis of research available as of the publication date can of course change at any time. The analysis in their article will accordingly be updated whenever new data become available. Readers are referred to a recent Annals editorial explaining how these updates may be easily accessed (7).The COVID-19 pandemic has placed the nation and the world under more stress than usual. Stress magnifies things; it can make fears loom larger and spawn hopes that may eventually prove illusory. Such has been the brief saga of COVID-19 and the RAS to this point. In any case, it comes as a welcome relief that we have clarification on at least 1 aspect of this pandemic.References1. Vaduganathan M, Vardeny O, Michel T, et al. Renin-angiotensin-aldosterone system inhibitors in patients with COVID-19. N Engl J Med. 2020;382:1653-9. [PMID: 32227760] doi:10.1056/NEJMsr2005760 CrossrefMedlineGoogle Scholar2. Esler M, Esler D. Can angiotensin receptor-blocking drugs perhaps be harmful in the COVID-19 pandemic? J Hypertens. 2020;38:781-2. [PMID: 32195824] doi:10.1097/HJH.0000000000002450 CrossrefMedlineGoogle Scholar3. Mackey K, King VJ, Gurley S, et al. Risks and impact of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers on SARS-CoV-2 infection in adults. A living systematic review. Ann Intern Med. 2020;173:195-203. doi:10.7326/M20-1515 LinkGoogle Scholar4. Alexandre J, Cracowski JL, Richard V, et al; ‘Drugs, COVID-19' Working Group of the French Society of Pharmacology, Therapeutics. Renin-angiotensin-aldosterone system and COVID-19 infection. Ann Endocrinol (Paris). 2020. [PMID: 32370986] doi:10.1016/j.ando.2020.04.005 CrossrefMedlineGoogle Scholar5. Pflugfelder PW, Baird MG, Tonkon MJ, et al. Clinical consequences of angiotensin-converting enzyme inhibitor withdrawal in chronic heart failure: a double-blind, placebo-controlled study of quinapril. The Quinapril Heart Failure Trial Investigators. J Am Coll Cardiol. 1993;22:1557-63. [PMID: 8227822] CrossrefMedlineGoogle Scholar6. Jarcho JA, Ingelfinger JR, Hamel MB, et al. Inhibitors of the renin-angiotensin-aldosterone system and COVID-19 [Editorial]. N Engl J Med. 2020. [PMID: 32356625] doi:10.1056/NEJMe2012924 CrossrefMedlineGoogle Scholar7. Laine C, Taichman DB, Guallar E, et al. Keeping up with emerging evidence in (almost) real time. Ann Intern Med. 2020. [PMID: 32369539] doi:10.7326/M20-2627 LinkGoogle Scholar Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAuthors: William G. KussmaulIII, MDAffiliations: Media, Pennsylvania (W.G.K.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M20-3047.Corresponding Author: William G. Kussmaul III, MD, 1343 West Baltimore Pike, E-401, Media, PA 19063; e-mail, w.kussmaul@verizon.net.This article was published at Annals.org on 15 May 2020. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoRisks and Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers on SARS-CoV-2 Infection in Adults Katherine Mackey , Valerie J. King , Susan Gurley , Michael Kiefer , Erik Liederbauer , Kathryn Vela , Payten Sonnen , and Devan Kansagara Metrics Cited byPatterns of pharmaceuticals use during the first wave of COVID-19 pandemic in Athens, Greece as revealed by wastewater-based epidemiologyCurrent Understanding of Clinical Manifestations of COVID-19 in Glomerular Disease 4 August 2020Volume 173, Issue 3Page: 237-238KeywordsAngiotensin converting enzyme inhibitorCOVID-19DrugsFearHypertensionObservational studiesReasoningSARS coronavirusSystematic reviewsUpper respiratory tract infections ePublished: 15 May 2020 Issue Published: 4 August 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...