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

Letters25 June 2020Update Alert: Risks and Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers on SARS-CoV-2 Infection in AdultsFREEDevan Kansagara, MD, MCR, Katherine Mackey, MD, MPP, and Kathryn Vela, MLIS, AHIPDevan Kansagara, MD, MCRVA Portland Health Care System, Portland, Oregon (D.K., K.M., K.V.), Katherine Mackey, MD, MPPVA Portland Health Care System, Portland, Oregon (D.K., K.M., K.V.), and Kathryn Vela, MLIS, AHIPVA Portland Health Care System, Portland, Oregon (D.K., K.M., K.V.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/L20-0887 SectionsSupplemental MaterialAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail In this first monthly update of our living review (1), we searched MEDLINE (Ovid) weekly from 4 May to 8 June 2020 using the same search strategy described in the original review, and we also identified additional citations from consultation with content experts. Searches yielded 138 results; independent dual review of these records identified 4 new studies (see Supplement Tables 1 and 2) and 2 in-progress trials for inclusion.New EvidenceOne new retrospective cohort study examined the association between angiotensin-converting enzyme inhibitor (ACEI) or angiotensin-receptor blocker (ARB) use and the likelihood of testing positive for COVID-19 (2). This study included all patients who had testing in 1 health system in 2 different states; patients with symptoms were prioritized for testing at the time, so most patients were likely to have been symptomatic. As in the previous review that identified 3 similar studies, neither ACEI nor ARB use was associated with likelihood of testing positive for COVID-19.This study also examined the association between ACEI or ARB use and COVID-19 illness severity. It found use of these medications was associated with a moderate increase in hospitalization and intensive care unit admission risk but not risk for mechanical ventilation (2). We found an additional 3 new studies evaluating the association between ACEI or ARB use and COVID-19 illness severity. Two were small single-center retrospective cohort studies from China that found that ACEI or ARB use was not associated with an increased risk for death or severe COVID-19 illness (3, 4). A nationwide retrospective cohort study from Korea similarly found that these medications were not associated with severity of illness after adjustment for demographic characteristics, comorbid conditions, and hospital type (5).The 2 studies from China included small, highly select patient populations and did not describe in detail how ACEI or ARB exposure was determined. The 2 larger studies were generally methodologically sound, although 1 study cautioned that the number of patients treated with ACEIs or ARBs who had the outcomes of intensive care unit admission or mechanical ventilation was small (2). (See Supplement Table 3 for methodological strengths and weaknesses of the studies.)Of note, 1 international study that examined the association between ACEIs or ARBs and severity of COVID-19 illness has since been retracted by the journal in which it was published (6). We will no longer consider results of this study in determining overall effects or certainty of evidence.Overall, the addition of the new studies and the retraction of 1 prior study does not change the findings or certainty of evidence ratings we reported in the original review.In-Progress TrialsWe identified 2 randomized controlled trials, currently in progress, that will compare the effects of continuing or withdrawing ACEI or ARB treatment on clinical outcomes in patients hospitalized with COVID-19. One is a U.S. study (7) and the other is a Brazilian study (8), and both are expected to be completed by the end of 2020.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. Mehta N, Kalra A, Nowacki AS, et al. Association of use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers with testing positive for coronavirus disease 2019 (COVID-19). JAMA Cardiol. 2020. [PMID: 32369097] doi:10.1001/jamacardio.2020.1855 CrossrefMedlineGoogle Scholar3. Chen Y, Yang D, Cheng B, et al. Clinical characteristics and outcomes of patients with diabetes and COVID-19 in association with glucose-lowering medication. Diabetes Care. 2020;43:1399-1407. [PMID: 32409498] doi:10.2337/dc20-0660 CrossrefMedlineGoogle Scholar4. Huang Z, Cao J, Yao Y, et al. The effect of RAS blockers on the clinical characteristics of COVID-19 patients with hypertension. Ann Transl Med. 2020;8:430. [PMID: 32395474] doi:10.21037/atm.2020.03.229 CrossrefMedlineGoogle Scholar5. Jung SY, Choi JC, You SH, et al. Association of renin-angiotensin-aldosterone system inhibitors with COVID-19-related outcomes in Korea: a nationwide population-based cohort study. Clin Infect Dis. 2020. [PMID: 32442285] doi:10.1093/cid/ciaa624 CrossrefMedlineGoogle Scholar6. Mehra MR, Desai SS, Kuy S, et al. Retraction: cardiovascular disease, drug therapy, and mortality in covid-19. N Engl J Med. DOI: 10.1056/NEJMoa2007621 [Letter]. N Engl J Med. 2020. doi:10.1056/NEJMc2021225 CrossrefGoogle Scholar7. Elimination or Prolongation of ACE Inhibitors and ARB in Coronavirus Disease 2019 (REPLACECOVID). ClinicalTrials.gov: NCT04338009. Updated 24 April 2020. Accessed at https://clinicaltrials.gov/ct2/show/NCT04338009 on 18 June 2020. Google Scholar8. Angiotensin Receptor Blockers and Angiotensin-converting Enzyme Inhibitors and Adverse Outcomes in Patients With COVID19 (BRACE-CORONA). ClinicalTrials.gov: NCT04364893. Updated 28 April 2020. Accessed at https://clinicaltrials.gov/ct2/show/NCT04364893 on 18 June 2020. Google Scholar Comments 0 Comments Sign In to Submit A Comment Author, Article, and Disclosure InformationAuthors: Devan Kansagara, MD, MCR; Katherine Mackey, MD, MPP; Kathryn Vela, MLIS, AHIPAffiliations: VA Portland Health Care System, Portland, Oregon (D.K., K.M., 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: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L20-0887.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 25 June 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 2: 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 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 6: 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 7: 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 byPast, present and future of living systematic review: a bibliometrics analysisA comprehensive guide to the pharmacologic regulation of angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptorMortality, Severity, and Hospital Admission among COVID-19 Patients with ACEI/ARB Use: A Meta-Analysis Stratifying Countries Based on Response to the First Wave of the PandemicObesity, vitamin D deficiency and old age a serious combination with respect to coronavirus disease-2019 severity and outcome 4 August 2020Volume 173, Issue 3 Page: W66 Keywords Angiotensin converting enzyme inhibitor Angiotensin receptor blocker Cohort studies COVID-19 Disclosure Hospitalizations Intensive care units Patients Population statistics Ventilators ePublished: 25 June 2020 Issue Published: 4 August 2020 PDF downloadLoading ...