Update Alert 6: 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)

Letters1 December 2020Update Alert 6: 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, Devan Kansagara, MD, MCRVA Portland Health Care System, Portland, Oregon, and Kathryn Vela, MLIS, AHIPVA Portland Health Care System, Portland, OregonAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L20-1355 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail An update is available for this article.We searched MEDLINE (Ovid) weekly from 29 September to 26 October 2020 using the same search strategy as described in the original review (1). We did not limit the search by language. This search update yielded 64 results (de-duplicated), and after an independent dual-review process, we identified 15 new studies meeting our inclusion criteria—12 observational studies and 3 systematic reviews with meta-analyses.New EvidenceFindings from 1 new observational study found no evidence of an association with angiotensin-converting enzyme inhibitor (ACEI) or angiotensin-receptor blocker (ARB) use and risk for coronavirus disease 2019 (COVID-19) (2). Findings from an additional 11 new observational studies did not demonstrate an association between use of ACEIs or ARBs and worse outcomes in COVID-19 (3–13). These findings are supported by 3 new systematic reviews with meta-analyses (14–16).Overall, inclusion of 15 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 or 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. [PMID: 32422062] doi:10.7326/M20-1515 LinkGoogle Scholar2. Dublin S, Walker R, Floyd JS, et al. Renin-angiotensin-aldosterone system inhibitors and COVID-19 infection or hospitalization: a cohort study. Am J Hypertens. 2020. [PMID: 33048112] doi:10.1093/ajh/hpaa168 CrossrefGoogle Scholar3. Braude P, Carter B, Short R, et al. The influence of ACE inhibitors and ARBs on hospital length of stay and survival in people with COVID-19. Int J Cardiol Heart Vasc. 2020;31:100660. [PMID: 33083516] doi:10.1016/j.ijcha.2020.100660 MedlineGoogle Scholar4. 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RAAS inhibitors are not associated with mortality in COVID-19 patients: findings from an observational multicenter study in Italy and a meta-analysis of 19 studies. Vascul Pharmacol. 2020;135:106805. [PMID: 32992048] doi:10.1016/j.vph.2020.106805 CrossrefMedlineGoogle Scholar8. Georges JL, Cochet H, Roger G, et al. Association of hypertension and antihypertensive agents and the severity of COVID-19 pneumonia: a monocentric French prospective study. Ann Cardiol Angeiol (Paris). 2020;69:247-254. [PMID: 33039120] doi:10.1016/j.ancard.2020.09.030 CrossrefMedlineGoogle Scholar9. Feng Z, Li J, Yao S, et al. Clinical factors associated with progression and prolonged viral shedding in COVID-19 patients: a multicenter study. Aging Dis. 2020;11:1069-1081. [PMID: 33014523] doi:10.14336/AD.2020.0630 CrossrefMedlineGoogle Scholar10. Hu J, Zhang X, Zhang X, et al. COVID-19 is more severe in patients with hypertension; ACEI/ARB treatment does not influence clinical severity and outcome [Letter]. J Infect. 2020. [PMID: 32474032] doi:10.1016/j.jinf.2020.05.056 CrossrefGoogle Scholar11. Palazzuoli A, Mancone M, De Ferrari, et al. Antecedent administration of angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists and survival after hospitalization for COVID-19 syndrome. J Am Heart Assoc. 2020;9:e017364. [PMID: 33023356] doi:10.1161/JAHA.120.017364 CrossrefMedlineGoogle Scholar12. Rodilla E, Saura A, Jiménez I, et al. Association of hypertension with all-cause mortality among hospitalized patients with COVID-19. J Clin Med. 2020;9. [PMID: 32998337] doi:10.3390/jcm9103136 CrossrefMedlineGoogle Scholar13. Yahyavi A, Hemmati N, Derakhshan P, et al. Angiotensin enzyme inhibitors and angiotensin receptor blockers as protective factors in COVID-19 mortality: a retrospective cohort study. Intern Emerg Med. 2020. [PMID: 33085063] doi:10.1007/s11739-020-02523-9 CrossrefMedlineGoogle Scholar14. Kurdi A, Abutheraa N, Akil L, et al. A systematic review and meta-analysis of the use of renin-angiotensin system drugs and COVID-19 clinical outcomes: what is the evidence so far. Pharmacol Res Perspect. 2020;8:e00666. [PMID: 33084232] doi:10.1002/prp2.666 CrossrefMedlineGoogle Scholar15. Wang Y, Chen B, Li Y, et al. The use of renin-angiotensin-aldosterone system (RAAS) inhibitors is associated with a lower risk of mortality in hypertensive COVID-19 patients: a systematic review and meta-analysis. J Med Virol. 2020. [PMID: 33095513] doi:10.1002/jmv.26625 CrossrefGoogle Scholar16. Xu J, Teng Y, Shang L, et al. The effect of prior ACEI/ARB treatment on COVID-19 susceptibility and outcome: a systematic review and meta-analysis. Clin Infect Dis. 2020. [PMID: 33079200] doi:10.1093/cid/ciaa1592 Google Scholar Comments0 CommentsSign 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, OregonDisclaimer: 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=L20-1355.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 1 December 2020. 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