Update Alert 2: Risks and Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers on SARS-CoV-2 Infection in Adults
Authors: Katherine Mackey, Devan Kansagara, Kathryn Vela
Journal: Annals of Internal Medicine (2020)

Letters23 July 2020Update Alert 2: Risks and Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers on SARS-CoV-2 Infection in AdultsFREEKatherine Mackey, MD, MPP, Devan Kansagara, MD, MCR, and Kathryn Vela, MLIS, AHIPKatherine Mackey, MD, MPPVA Portland Health Care System, Portland, Oregon (K.M., D.K., K.V.)Search for more papers by this author, Devan Kansagara, MD, MCRVA Portland Health Care System, Portland, Oregon (K.M., D.K., K.V.)Search for more papers by this author, and Kathryn Vela, MLIS, AHIPVA Portland Health Care System, Portland, Oregon (K.M., D.K., K.V.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L20-0969 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail In this second monthly update of our living review (1), we searched MEDLINE (Ovid) weekly from 9 June to 6 July 2020 using the same search strategy as described in the original review. We did not limit by language. This search update yielded 91 results (de-duplicated). After an independent dual-review process, we identified 3 new meta-analyses, 5 new observational studies, and 1 in-progress trial for inclusion.New EvidenceResults of 3 new meta-analyses (2–4) evaluating the association of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin-receptor blocker (ARB) use with coronavirus disease 2019 (COVID-19) illness severity are consistent with the findings that we reported in the original manuscript. Five new observational studies also examine this association. Four of these studies found that use of ACEIs or ARBs is not associated with more severe COVID-19 illness (5–8). In a retrospective study of 113 patients hospitalized with COVID-19 in Turkey, use of ACEIs/ARBs was associated with higher in-hospital mortality (9). However, a major limitation of the study is that the group of patients taking ACEIs/ARBs were older and more likely to have coronary artery disease than the non–ACEI/ARB group.Overall, inclusion of these 3 new meta-analyses and 5 new observational studies does not change the certainty of evidence rating we reported in the original manuscript for key question 2—high-certainty evidence that ACEI or ARB use is not associated with more severe COVID-19 illness.In-Progress TrialsWe identified 1 randomized controlled trial that is currently in progress in the Netherlands comparing ARB therapy (valsartan) with placebo on intensive care unit admission, mechanical ventilation, and death among hospitalized adults with COVID-19 (10). The estimated study completion date is December 2021.Citation UpdateA study by Yang and colleagues (11) that was included in our original manuscript as a preprint has now been published.References1. 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. [PMID: 32422062]. doi:10.7326/M20-1515 LinkGoogle Scholar2. Flacco ME, Acuti Martellucci C, Bravi F, et al. Treatment with ACE inhibitors or ARBs and risk of severe/lethal COVID-19: a meta-analysis. Heart. 2020. [PMID: 32611676] doi:10.1136/heartjnl-2020-317336 CrossrefMedlineGoogle Scholar3. Grover A, Oberoi M. A systematic review and meta-analysis to evaluate the clinical outcomes in COVID-19 patients on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Eur Heart J Cardiovasc Pharmacother. 2020. [PMID: 32542337] doi:10.1093/ehjcvp/pvaa064 CrossrefMedlineGoogle Scholar4. Pirola CJ, Sookoian S. Estimation of renin-angiotensin-aldosterone-system (RAAS)-inhibitor effect on COVID-19 outcome: a meta-analysis. J Infect. 2020. [PMID: 32474043] doi:10.1016/j.jinf.2020.05.052 CrossrefMedlineGoogle Scholar5. Bravi F, Flacco ME, Carradori T, et al. Predictors of severe or lethal COVID-19, including angiotensin converting enzyme inhibitors and angiotensin II receptor blockers, in a sample of infected Italian citizens. PLoS One. 2020;15:e0235248. [PMID: 32579597] doi:10.1371/journal.pone.0235248 CrossrefMedlineGoogle Scholar6. Choi MH, Ahn H, Ryu HS, et al. Clinical characteristics and disease progression in early-stage COVID-19 patients in South Korea. J Clin Med. 2020;9. [PMID: 32585855] doi:10.3390/jcm9061959 CrossrefMedlineGoogle Scholar7. Felice C, Nardin C, Di Tanna GL, et al. Use of RAAS inhibitors and risk of clinical deterioration in COVID-19: results from an Italian cohort of 133 hypertensives. Am J Hypertens. 2020. [PMID: 32511678] doi:10.1093/ajh/hpaa096 CrossrefMedlineGoogle Scholar8. Fosbøl EL, Butt JH, Østergaard L, et al. Association of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use with COVID-19 diagnosis and mortality. JAMA. 2020. [PMID: 32558877] doi:10.1001/jama.2020.11301 CrossrefMedlineGoogle Scholar9. Selçuk M, Çinar T, Keskin M, et al. Is the use of ACE inb/ARBs associated with higher in-hospital mortality in Covid-19 pneumonia patients? Clin Exp Hypertens. 2020;42:738-742. [PMID: 32569491] doi:10.1080/10641963.2020.1783549 CrossrefMedlineGoogle Scholar10. Gommans DHF, Nas J, Pinto-Sietsma SJ, et al; Event committee. Rationale and design of the PRAETORIAN-COVID trial: a double-blind, placebo-controlled randomized clinical trial with valsartan for prevention of acute respiratory distress syndrome in hospitalized patients with SARS-COV-2 Infection Disease. Am Heart J. 2020;226:60-68. [PMID: 32512291] doi:10.1016/j.ahj.2020.05.010 CrossrefMedlineGoogle Scholar11. Yang G, Tan Z, Zhou L, et al. Effects of angiotensin II receptor blockers and ACE (angiotensin-converting enzyme) inhibitors on virus infection, inflammatory status, and clinical outcomes in patients with COVID-19 and hypertension: a single-center retrospective study. Hypertension. 2020;76:51-58. [PMID: 32348166] doi:10.1161/HYPERTENSIONAHA.120.15143 CrossrefMedlineGoogle Scholar Comments 0 Comments Sign In to Submit A Comment Author, Article, and Disclosure InformationAuthors: Katherine Mackey, MD, MPP; Devan Kansagara, MD, MCR; Kathryn Vela, MLIS, AHIPAffiliations: VA Portland Health Care System, Portland, Oregon (K.M., D.K., K.V.)Disclaimer: The views expressed in this article are those of the authors and do not necessarily represent the views of the U.S. Department of Veterans Affairs or the U.S. government.Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L20-0969.Corresponding Author: Devan Kansagara, MD, MCR, VA Portland Health Care System, 3710 Southwest U.S. Veterans Hospital Road, Mail Code: R&D 71, Portland, OR 97239; e-mail, kansagar@ohsu.edu.This article was published at Annals.org on 23 July 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 Update Alert: Risks and Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers on SARS-CoV-2 Infection in Adults Devan Kansagara , Katherine Mackey , and Kathryn Vela Update Alert 3: Risks and Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers on SARS-CoV-2 Infection in Adults Katherine Mackey , Devan Kansagara , and Kathryn Vela Update Alert 4: Risks and Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers on SARS-CoV-2 Infection in Adults Katherine Mackey , Devan Kansagara , and Kathryn Vela Update Alert 5: Risks and Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers on SARS-CoV-2 Infection in Adults Katherine Mackey , Devan Kansagara , and Kathryn Vela Update Alert 8: Risks and Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers on SARS-CoV-2 Infection in Adults Katherine Mackey , Devan Kansagara , and Kathryn Vela Update Alert 9: Risks and Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers on SARS-CoV-2 Infection in Adults Katherine Mackey , Devan Kansagara , Kathryn Vela Update Alert 10: Risks and Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers on SARS-CoV-2 Infection in Adults Katherine Mackey , Devan Kansagara , Kathryn Vela Metrics Cited by3219 hospitalised patients with COVID-19 in Southeast Michigan: a retrospective case cohort studyManaging COVID-19 post viral Fatigue Syndrome 1 September 2020Volume 173, Issue 5 Page: W87 Keywords Angiotensin converting enzyme inhibitor Angiotensin receptor blocker COVID-19 Health care Intensive care units Mortality Observational studies Retrospective studies Stable coronary artery disease Ventilators ePublished: 23 July 2020 Issue Published: 1 September 2020 PDF downloadLoading ...