Update Alert 4: 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)

Letters22 September 2020Update Alert 4: 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/L20-1177 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail In this fourth monthly update of our living review (1), we searched MEDLINE (Ovid) weekly from 4 August to 31 August 2020 using the same search strategy as described in the original review. We did not limit the search by language. This search update yielded 82 results (de-duplicated), and after an independent dual-review process, we identified 24 new studies meeting our inclusion criteria—19 observational studies, 4 meta-analyses, and 1 systematic review (2–25).Findings from the 19 observational studies are overall consistent with prior evidence that found a lack of association between angiotensin-converting enzyme inhibitor (ACEI) and angiotensin-receptor blocker (ARB) use and more severe coronavirus disease 2019 (COVID-19) (2–20). Several studies suggest that use of ACEIs or ARBs before developing COVID-19 may be associated with improved outcomes (3, 4, 7, 11, 12).Two meta-analyses addressed our first key question about use of ACEIs and ARBs and COVID-19 risk, finding that neither ACEI nor ARB use is significantly associated with the odds of COVID-19 (22, 24). Three meta-analyses addressed our second key question about ACEI and ARB use and COVID-19 disease severity, finding that use of these medications was not associated with the risk for more severe disease (21–23).Overall, inclusion of 24 studies from this search update does not change the certainty of evidence rating we reported in the original manuscript for key questions 1 or 2. Studies have not examined the benefits and harms of initiating ACEIs and ARBs (that is, new users) in COVID-19 treatment; therefore, evidence for key question 3 remains unclear.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. doi:10.7326/M20-1515 LinkGoogle Scholar2. Bae DJ, Tehrani DM, Rabadia SV, et al. Angiotensin converting enzyme inhibitor and angiotensin II receptor blocker use among outpatients diagnosed with COVID-19. Am J Cardiol. 2020;132:150-157. [PMID: 32819683] doi:10.1016/j.amjcard.2020.07.007 CrossrefMedlineGoogle Scholar3. Barochiner J, Martínez R. Use of inhibitors of the renin-angiotensin system in hypertensive patients and COVID-19 severity: a systematic review and meta-analysis. J Clin Pharm Ther. 2020. [PMID: 32767823] doi:10.1111/jcpt.13246 CrossrefMedlineGoogle Scholar4. Chen FF, Zhong M, Liu Y, et al. The characteristics and outcomes of 681 severe cases with COVID-19 in China. J Crit Care. 2020;60:32-37. [PMID: 32736197] doi:10.1016/j.jcrc.2020.07.003 CrossrefMedlineGoogle Scholar5. Dalan R, Ang LW, Tan WYT, et al. The association of hypertension and diabetes pharmacotherapy with COVID-19 severity and immune signatures: an observational study. Eur Heart J Cardiovasc Pharmacother. 2020. [PMID: 32766831] doi:10.1093/ehjcvp/pvaa098 CrossrefMedlineGoogle Scholar6. Gormez S, Ekicibasi E, Degirmencioglu A, et al. Association between renin-angiotensin-aldosterone system inhibitor treatment, neutrophil-lymphocyte ratio, D-dimer and clinical severity of COVID-19 in hospitalized patients: a multicenter, observational study. J Hum Hypertens. 2020. [PMID: 32839534] doi:10.1038/s41371-020-00405-3 CrossrefMedlineGoogle Scholar7. Hippisley-Cox J, Young D, Coupland C, et al. Risk of severe COVID-19 disease with ACE inhibitors and angiotensin receptor blockers: cohort study including 8.3 million people. Heart. 2020;106:1503-1511. [PMID: 32737124] doi:10.1136/heartjnl-2020-317393 CrossrefMedlineGoogle Scholar8. Huang W, Li T, Ling Y, et al. Effects of angiotensin converting enzyme inhibitor/angiotensin receptor blocker on clinical characteristics of coronavirus disease 2019 patients with hypertension. Zhonghua Nei Ke Za Zhi. 2020;59:689-694. [PMID: 32838499] doi:10.3760/cma.j.cn112138-20200229-00155 CrossrefMedlineGoogle Scholar9. Martínez-Del Río J, Piqueras-Flores J, Nieto-Sandoval Martín de la Sierra P, et al. Comparative analysis between the use of renin-angiotensin system antagonists and clinical outcomes of hospitalized patients with COVID-19 respiratory infection. Med Clin (Barc). 2020. [PMID: 32782110] doi:10.1016/j.medcli.2020.07.004 CrossrefMedlineGoogle Scholar10. Matsuzawa Y, Ogawa H, Kimura K, et al. Renin-angiotensin system inhibitors and the severity of coronavirus disease 2019 in Kanagawa, Japan: a retrospective cohort study. Hypertens Res. 2020. [PMID: 32820236] doi:10.1038/s41440-020-00535-8 CrossrefMedlineGoogle Scholar11. Megaly M, Glogoza M. Renin-angiotensin system antagonists are associated with lower mortality in hypertensive patients with COVID-19 [Letter]. Scott Med J. 2020:36933020949219. [PMID: 32807019] doi:10.1177/0036933020949219 CrossrefMedlineGoogle Scholar12. Pan W, Zhang J, Wang M, et al. Clinical features of COVID-19 in patients with essential hypertension and the impacts of renin-angiotensin-aldosterone system inhibitors on the prognosis of COVID-19 patients. Hypertension. 2020;76:732-741. [PMID: 32654555] doi:10.1161/HYPERTENSIONAHA.120.15289 CrossrefMedlineGoogle Scholar13. Raisi-Estabragh Z, McCracken C, Ardissino M, et al. Renin-angiotensin-aldosterone system blockers are not associated with coronavirus disease 2019 (COVID-19) hospitalization: study of 1,439 UK Biobank cases. Front Cardiovasc Med. 2020;7:138. [PMID: 32766285] doi:10.3389/fcvm.2020.00138 CrossrefMedlineGoogle Scholar14. Ran J, Song Y, Zhuang Z, et al. Blood pressure control and adverse outcomes of COVID-19 infection in patients with concomitant hypertension in Wuhan, China. Hypertens Res. 2020. [PMID: 32855527] doi:10.1038/s41440-020-00541-w CrossrefMedlineGoogle Scholar15. Rey JR, Caro-Codón J, Rosillo SO, et al. Heart failure in covid-19 patients: prevalence, incidence and prognostic implications. Eur J Heart Fail. 2020. [PMID: 32833283] doi:10.1002/ejhf.1990 CrossrefMedlineGoogle Scholar16. Shah P, Owens J, Franklin J, et al. Baseline use of angiotensin-converting enzyme inhibitor/AT1 blocker and outcomes in hospitalized coronavirus disease 2019 African-American patients. J Hypertens. 2020. [PMID: 32740406] doi:10.1097/HJH.0000000000002584 CrossrefMedlineGoogle Scholar17. Son M, Seo J, Yang S. Association between renin-angiotensin-aldosterone system inhibitors and COVID-19 infection in South Korea. Hypertension. 2020;76:742-749. [PMID: 32654557] doi:10.1161/HYPERTENSIONAHA.120.15464 CrossrefMedlineGoogle Scholar18. Tan ND, Qiu Y, Xing XB, et al. Associations between angiotensin-converting enzyme inhibitors and angiotensin II receptor blocker use, gastrointestinal symptoms, and mortality among patients with COVID-19. Gastroenterology. 2020;159:1170-1172. [PMID: 32422208] doi:10.1053/j.gastro.2020.05.034 CrossrefMedlineGoogle Scholar19. Trifirò G, Massari M, Da Cas R, et al. ITA-COVID-19: RAAS Inhibitor Group.. Renin-angiotensin-aldosterone system inhibitors and risk of death in patients hospitalised with COVID-19: a retrospective Italian cohort study of 43,000 patients. Drug Saf. 2020. [PMID: 32852721] doi:10.1007/s40264-020-00994-5 CrossrefMedlineGoogle Scholar20. Yuan Y, Liu D, Zeng S, et al. In-hospital use of ACEI/ARB is associated with lower risk of mortality and critic illness in COVID-19 patients with hypertension [Letter]. J Infect. 2020. [PMID: 32800800] doi:10.1016/j.jinf.2020.08.014 CrossrefMedlineGoogle Scholar21. Baral R, White M, Vassiliou VS. Effect of renin-angiotensin-aldosterone system inhibitors in patients with COVID-19: a systematic review and meta-analysis of 28,872 patients. Curr Atheroscler Rep. 2020;22:61. [PMID: 32830286] doi:10.1007/s11883-020-00880-6 CrossrefMedlineGoogle Scholar22. Liu X, Long C, Xiong Q, et al. Association of angiotensin converting enzyme inhibitors and angiotensin II receptor blockers with risk of COVID-19, inflammation level, severity, and death in patients with COVID-19: a rapid systematic review and meta-analysis. Clin Cardiol. 2020. [PMID: 32757246] doi:10.1002/clc.23421 CrossrefMedlineGoogle Scholar23. Salah HM, Calcaterra G, Mehta JL. Renin-angiotensin system blockade and mortality in patients with hypertension and COVID-19 infection. J Cardiovasc Pharmacol Ther. 2020:1074248420947628. [PMID: 32748634] doi:10.1177/1074248420947628 CrossrefMedlineGoogle Scholar24. Usman MS, Siddiqi TJ, Khan MS, et al. A meta-analysis of the relationship between renin-angiotensin-aldosterone system inhibitors and COVID-19 [Letter]. Am J Cardiol. 2020;130:159-161. [PMID: 32624189] doi:10.1016/j.amjcard.2020.05.038 CrossrefMedlineGoogle Scholar25. Singh AK, Gupta R, Misra A. Comorbidities in COVID-19: outcomes in hypertensive cohort and controversies with renin angiotensin system blockers. Diabetes Metab Syndr. 2020;14:283-287. [PMID: 32283499] doi:10.1016/j.dsx.2020.03.016 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=L20-1177.Corresponding Author: Katherine Mackey, MD, MPP, VA Portland Health Care System, 3710 SW US Veterans Hospital Road, Portland, OR 97239; e-mail, Katherine.Mackey@va.gov.This article was published at Annals.org on 22 September 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 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 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 analysisExploring Drugs and Vaccines Associated with Altered Risks and Severity of COVID-19: A UK Biobank Cohort Study of All ATC Level-4 Drug Categories Reveals Repositioning Opportunities 3 November 2020Volume 173, Issue 9 Page: W147-W148 Keywords Angiotensin converting enzyme inhibitor Angiotensin receptor blocker Conflicts of interest COVID-19 Disclosure Health care Observational studies Systematic reviews Veteran care ePublished: 22 September 2020 Issue Published: 3 November 2020 PDF downloadLoading ...