{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T11:55:38Z","timestamp":1783338938287,"version":"3.54.6"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T00:00:00Z","timestamp":1620777600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T00:00:00Z","timestamp":1620777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["#COV20\/00027"],"award-info":[{"award-number":["#COV20\/00027"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006302","name":"Universidad de Alcal\u00e1","doi-asserted-by":"publisher","award":["#COVID-19 UAH 2019\/00003\/016\/001\/028"],"award-info":[{"award-number":["#COVID-19 UAH 2019\/00003\/016\/001\/028"]}],"id":[{"id":"10.13039\/501100006302","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fundaci\u00f3n para la Investigaci\u00f3n Biom\u00e9dica del Hospital Universitario Principe de Asturias"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Med"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>In the first wave of the COVID-19 pandemic, the hypothesis that angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) increased the risk and\/or severity of the disease was widely spread. Consequently, in many hospitals, these drugs were discontinued as a \u201cprecautionary measure\u201d. We aimed to assess whether the in-hospital discontinuation of ARBs or ACEIs, in real-life conditions, was associated with a reduced risk of death as compared to their continuation and also to compare head-to-head the continuation of ARBs with the continuation of ACEIs.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Adult patients with a PCR-confirmed diagnosis of COVID-19 requiring admission during March 2020 were consecutively selected from 7 hospitals in Madrid, Spain. Among them, we identified outpatient users of ACEIs\/ARBs and divided them in two cohorts depending on treatment discontinuation\/continuation at admission. Then, they were followed-up until discharge or in-hospital death. An intention-to-treat survival analysis was carried out and hazard ratios (HRs), and their 95%CIs were computed through a Cox regression model adjusted for propensity scores of discontinuation and controlled by potential mediators.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Out of 625 ACEI\/ARB users, 340 (54.4%) discontinued treatment. The in-hospital mortality rates were 27.6% and 27.7% in discontinuation and continuation cohorts, respectively (HR=1.01; 95%CI 0.70\u20131.46). No difference in mortality was observed between ARB and ACEI discontinuation (28.6% vs. 27.1%, respectively), while a significantly lower mortality rate was found among patients who continued with ARBs (20.8%, <jats:italic>N<\/jats:italic>=125) as compared to those who continued with ACEIs (33.1%, <jats:italic>N<\/jats:italic>=136; <jats:italic>p<\/jats:italic>=0.03). The head-to-head comparison (ARB vs. ACEI continuation) yielded an adjusted HR of 0.52 (95%CI 0.29\u20130.93), being especially notorious among males (HR=0.34; 95%CI 0.12\u20130.93), subjects older than 74 years (HR=0.46; 95%CI 0.25\u20130.85), and patients with obesity (HR=0.22; 95%CI 0.05\u20130.94), diabetes (HR=0.36; 95%CI 0.13\u20130.97), and heart failure (HR=0.12; 95%CI 0.03\u20130.97).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The discontinuation of ACEIs\/ARBs at admission did not improve the in-hospital survival. On the contrary, the continuation with ARBs was associated with a trend to a reduced mortality as compared to their discontinuation and to a significantly lower mortality risk as compared to the continuation with ACEIs, particularly in high-risk patients.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12916-021-01992-9","type":"journal-article","created":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T15:05:44Z","timestamp":1620831944000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Impact of in-hospital discontinuation with angiotensin receptor blockers or converting enzyme inhibitors on mortality of COVID-19 patients: a retrospective cohort study"],"prefix":"10.1186","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9119-8646","authenticated-orcid":false,"given":"Francisco J.","family":"de Abajo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Rodr\u00edguez-Miguel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Rodr\u00edguez-Mart\u00edn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Lerma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Garc\u00eda-Lled\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of MED-ACE2-COVID19 Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. J.","family":"de Abajo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Rodr\u00edguez-Miguel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Rodr\u00edguez-Mart\u00edn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Lerma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Garc\u00eda-Lled\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Barreira-Hern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Rodr\u00edguez-Puyol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O.","family":"Laosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Pedraza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Rodr\u00edguez-Ma\u00f1as","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Aguilar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"de Pablo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. A.","family":"G\u00e1lvez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Garc\u00eda-Luque","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Puerro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. M.","family":"Aparicio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Garc\u00eda-Rosado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Guti\u00e9rrez-Ortega","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Laredo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Gonz\u00e1lez-Rojano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"P\u00e9rez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Ascaso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Elvira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Mej\u00eda-Abril","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Zubiaur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Santos-Molina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Pintos-S\u00e1nchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Navares-G\u00f3mez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Abad-Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. A.","family":"Centeno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Sancho-Lopez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Payares-Herrera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Diago-Sempere","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,12]]},"reference":[{"key":"1992_CR1","unstructured":"O\u00b4Mara G. Could ACE inhibitors and particularly ARBs increase susceptibility to COVID-19 infection? BMJ. 2020;368 Available in https:\/\/www.bmj.com\/content\/368\/bmj.m406\/rr-13."},{"key":"1992_CR2","first-page":"m810","volume":"368","author":"R Sommerstein","year":"2020","unstructured":"Sommerstein R. Preventing a COVID-19 pandemic: ACE inhibitors as potential risk factor for fatal Covid-19. BMJ. 2020;368:m810. https:\/\/www.bmj.com\/content\/368\/bmj.m810\/rr-2.","journal-title":"BMJ"},{"issue":"4","key":"1992_CR3","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(20)30116-8","volume":"8","author":"L Fang","year":"2020","unstructured":"Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir Med. 2020;8(4):e21. https:\/\/doi.org\/10.1016\/S2213-2600(20)30116-8.","journal-title":"Lancet Respir Med"},{"issue":"25","key":"1992_CR4","doi-asserted-by":"publisher","first-page":"2431","DOI":"10.1056\/NEJMoa2006923","volume":"382","author":"G Mancia","year":"2020","unstructured":"Mancia G, Rea F, Ludegnani M, Apolone G, Corrao G. Renin-angiotensin-aldosterone system blockers and the risk of Covid-19. N Engl J Med. 2020;382(25):2431\u201340. https:\/\/doi.org\/10.1056\/NEJMoa2006923.","journal-title":"N Engl J Med"},{"issue":"25","key":"1992_CR5","doi-asserted-by":"publisher","first-page":"2441","DOI":"10.1056\/NEJMoa2008975","volume":"382","author":"H Reynolds","year":"2020","unstructured":"Reynolds H, Adhikari S, Pulgarin C, Troxel AB, Iturrate E, Johnson SB, et al. Renin-angiotensin-aldosterone system inhibitors and risk of COVID-19. N Engl J Med. 2020;382(25):2441\u20138. https:\/\/doi.org\/10.1056\/NEJMoa2008975.","journal-title":"N Engl J Med"},{"issue":"10238","key":"1992_CR6","doi-asserted-by":"publisher","first-page":"1705","DOI":"10.1016\/S0140-6736(20)31030-8","volume":"395","author":"FJ De Abajo","year":"2020","unstructured":"De Abajo FJ, Rodr\u00edguez-Martin S, Lerma V, Mej\u00eda-Abril G, Aguilar M, Garc\u00eda-Luque A, et al. Use of renin-angiotensin-aldosterone system inhibitors and risk of COVID-19 causing hospital admission: a case-population study. Lancet. 2020;395(10238):1705\u201314. https:\/\/doi.org\/10.1016\/S0140-6736(20)31030-8.","journal-title":"Lancet"},{"issue":"19","key":"1992_CR7","doi-asserted-by":"publisher","first-page":"1519","DOI":"10.1136\/heartjnl-2020-317336","volume":"106","author":"ME Flacco","year":"2020","unstructured":"Flacco ME, Martellucci CA, Bravi F, Parruti G, Cappadona R, Mascitelli A, et al. Treatment with ACE inhibitors or ARBs and risk of severe\/lethal COVID-19: a meta-analysis. Heart. 2020;106(19):1519\u201324. https:\/\/doi.org\/10.1136\/heartjnl-2020-317336.","journal-title":"Heart"},{"issue":"20","key":"1992_CR8","doi-asserted-by":"publisher","first-page":"30353","DOI":"10.1016\/j.jjcc.2020.10.015","volume":"S0914-5087","author":"L Ren","year":"2020","unstructured":"Ren L, Yu S, Xu W, Oveton JL, Chiamvimonvat N, Thai PN. Lack of association of antihypertensive drugs with the risk and severity of COVID-19: a meta-analysis. J Cardiol. 2020;S0914-5087(20):30353\u20131. https:\/\/doi.org\/10.1016\/j.jjcc.2020.10.015.","journal-title":"J Cardiol"},{"issue":"6","key":"1992_CR9","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1093\/ehjcvp\/pvaa056","volume":"6","author":"F Cannata","year":"2020","unstructured":"Cannata F, Chiarito M, Reimers B, Azzolini E, Ferrante G, My I, et al. Continuation versus discontinuation of ACE inhibitors or angiotensin II receptor blockers in COVID-19: effects on blood pressure control and mortality. Eur Heart J Cardiovasc Pharmacother. 2020;6(6):412\u20134. https:\/\/doi.org\/10.1093\/ehjcvp\/pvaa056.","journal-title":"Eur Heart J Cardiovasc Pharmacother"},{"issue":"8","key":"1992_CR10","doi-asserted-by":"publisher","first-page":"1256","DOI":"10.1093\/infdis\/jiaa447","volume":"222","author":"KW Lam","year":"2020","unstructured":"Lam KW, Chow KW, Vo J, Hou W, Li H, Richman PS, et al. Continued in-hospital angiotensin converting enzyme inhibitor and angiotensin II receptor blocker use in hypertensive COVID-19 patients is associated with positive clinical outcome. J Infect Dis. 2020;222(8):1256\u201364. https:\/\/doi.org\/10.1093\/infdis\/jiaa447.","journal-title":"J Infect Dis"},{"issue":"12","key":"1992_CR11","doi-asserted-by":"publisher","first-page":"1671","DOI":"10.1161\/CIRCRESAHA.120.317134","volume":"126","author":"P Zhang","year":"2020","unstructured":"Zhang P, Zhu L, Cai J, Lei F, Qin JJ, Xie J, et al. Association of inpatient use of angiotensin converting enzyme inhibitors and angiotensin ii receptor blockers with mortality among patients with hypertension hospitalised with COVID-19. Circ Res. 2020;126(12):1671\u201381. https:\/\/doi.org\/10.1161\/CIRCRESAHA.120.317134.","journal-title":"Circ Res"},{"key":"1992_CR12","doi-asserted-by":"publisher","first-page":"801","DOI":"10.34067\/kid.0003792020","volume":"1","author":"I Chaudhri","year":"2020","unstructured":"Chaudhri I, Koraishy FM, Bolotova O, Yoo J, Marcos LA, Taub E, et al. Outcomes associated with the use of renin-angiotensin-aldosterone system blockade in hospitalised patients with SARS-CoV-2 infection. Kidney 360. 2020;1:801\u20139. https:\/\/doi.org\/10.34067\/kid.0003792020.","journal-title":"Kidney 360"},{"issue":"17","key":"1992_CR13","doi-asserted-by":"publisher","first-page":"1653","DOI":"10.1056\/NEJMsr2005760","volume":"382","author":"M Vaduganathan","year":"2020","unstructured":"Vaduganathan M, Vardeny O, Michel T, McMurray JJV, Pfeffer MA, Solomon SD. Renin-angiotensin-aldosterone system inhibitors in patients with COVID-19. N Engl J Med. 2020;382(17):1653\u20139. https:\/\/doi.org\/10.1056\/NEJMsr2005760.","journal-title":"N Engl J Med"},{"issue":"21","key":"1992_CR14","doi-asserted-by":"publisher","first-page":"4825","DOI":"10.1111\/bph.15082","volume":"177","author":"K Sriram","year":"2020","unstructured":"Sriram K, Insel PA. A hypothesis for pathobiology and treatment of COVID-19: the centrality of ACE1\/ACE2 imbalance. Br J Pharmacol. 2020;177(21):4825\u201344. https:\/\/doi.org\/10.1111\/bph.15082.","journal-title":"Br J Pharmacol"},{"key":"1992_CR15","doi-asserted-by":"publisher","first-page":"102907","DOI":"10.1016\/j.ebiom.2020.102907","volume":"58","author":"M Chung","year":"2020","unstructured":"Chung M, Karnik S, Saef J, Bergman C, Barnard J, Lederman MM, et al. SARS-CoV-2 and ACE2: the biology and clinical data settling the ARB and ACEI controversy. EBioMedicine. 2020;58:102907. https:\/\/doi.org\/10.1016\/j.ebiom.2020.102907.","journal-title":"EBioMedicine"},{"issue":"12","key":"1992_CR16","doi-asserted-by":"publisher","first-page":"e140","DOI":"10.1161\/CIRCRESAHA.120.317205","volume":"126","author":"JB Cohen","year":"2020","unstructured":"Cohen JB, Hanff TC, South AM, Sparks MA, Hiremath S, Bress AP, et al. Response by Cohen et al to letter regarding article, \u201cassociation of inpatient use of angiotensin-converting enzyme inhibitors and angiotensin ii receptor blockers with mortality among patients with hypertension hospitalised with COVID-19\u201d. Circ Res. 2020;126(12):e140\u20131. https:\/\/doi.org\/10.1161\/CIRCRESAHA.120.317205.","journal-title":"Circ Res"},{"issue":"2","key":"1992_CR17","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1097\/HJH.0000000000002658","volume":"39","author":"A Lahens","year":"2020","unstructured":"Lahens A, Mullaert J, Gressens S, Gault N, Flamant M, Deconinck L, et al. Association between renin-angiotensin-aldosterone system blockers and outcome in coronavirus disease 2019: analysing in-hopsital exposure generates a biased seemingly protective effect of treatment. J Hypertens. 2020;39(2):367\u201375. https:\/\/doi.org\/10.1097\/HJH.0000000000002658.","journal-title":"J Hypertens"},{"issue":"3","key":"1992_CR18","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1001\/jama.2020.25864","volume":"325","author":"RD Lopes","year":"2021","unstructured":"Lopes RD, Macedo AVS, de Barros E, Silva PGM, Moll-Bernardes RJ, Dos Santos TM, et al. Effect of discontinuing vs continuing angiotensin-converting enzyme inhibitors and angiotensin ii receptor blockers on days alive and out of the hospital in patients admitted with COVID-19: a randomised clinical trial. JAMA. 2021;325(3):254\u201364. 33464336. https:\/\/doi.org\/10.1001\/jama.2020.25864.","journal-title":"JAMA"},{"key":"1992_CR19","doi-asserted-by":"publisher","unstructured":"Cohen JB, Handff TC, William P, Sweitzer N, Rosado-Santander NR, Medina C, et al. Continuation versus discontinuation of renin-angiotensin system inhibitors in patients admitted to hospital with COVID-19: a prospective, randomised, open-label trial. Lancet Respir Med. 2021; https:\/\/doi.org\/10.1016\/S2213-2600(20)30558-0.","DOI":"10.1016\/S2213-2600(20)30558-0"},{"issue":"13","key":"1992_CR20","doi-asserted-by":"publisher","first-page":"1474","DOI":"10.1016\/j.jacc.2018.01.058","volume":"71","author":"FH Messerli","year":"2018","unstructured":"Messerli FH, Bangalore S, Bavishi C, Rimoldi SF. Angiontensin-converting enzyme inhibitors in hypertension \u2013 to use or not use? J Am Coll Cardiol. 2018;71(13):1474\u201382. https:\/\/doi.org\/10.1016\/j.jacc.2018.01.058.","journal-title":"J Am Coll Cardiol"},{"issue":"25","key":"1992_CR21","doi-asserted-by":"publisher","first-page":"3038","DOI":"10.1002\/sim.3697","volume":"28","author":"PS Austin","year":"2009","unstructured":"Austin PS. Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples. Stat Med. 2009;28(25):3038\u2013107. https:\/\/doi.org\/10.1002\/sim.3697.","journal-title":"Stat Med"},{"issue":"3","key":"1992_CR22","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1080\/00273171.2011.568786","volume":"46","author":"PS Austin","year":"2011","unstructured":"Austin PS. An introduction to propensity score methods for reducing the effects of confounding in observational studies. Multivariate Behav Res. 2011;46(3):399\u2013424. https:\/\/doi.org\/10.1080\/00273171.2011.568786.","journal-title":"Multivariate Behav Res"},{"key":"1992_CR23","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1007\/978-1-4614-1353-0_6","volume-title":"Survival analysis, in regression methods in biostatistics","author":"E Vittinghof","year":"2012","unstructured":"Vittinghof E, Gludden DV, Shiboski SC, McCulloch CE. Survival Analysis. In: Survival analysis, in regression methods in biostatistics. 2nd ed. New York: Springer; 2012. p. 203\u201359.","edition":"2"},{"key":"1992_CR24","first-page":"183","volume-title":"Modern Epidemiology","author":"MM Glymour","year":"2008","unstructured":"Glymour MM, Greenland S. Causal diagrams. In: Rothman K, Greeland S, Lash TL, editors. Modern Epidemiology. 3rd ed. Philadelphia: Wolters Kuwer\/Lippincott Williams & Wilkins; 2008. p. 183\u2013209.","edition":"3"},{"issue":"5","key":"1992_CR25","doi-asserted-by":"publisher","first-page":"1511","DOI":"10.1093\/ije\/dyt127","volume":"42","author":"L Richiardi","year":"2013","unstructured":"Richiardi L, Bellocco R, Zugna D. Mediation analysis in epidemiology: methods, interpretation and bias. Int J Epidemiol. 2013;42(5):1511\u20139. https:\/\/doi.org\/10.1093\/ije\/dyt127.","journal-title":"Int J Epidemiol"},{"issue":"7382","key":"1992_CR26","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1136\/bmj.326.7382.219","volume":"326","author":"DG Altman","year":"2003","unstructured":"Altman DG, Bland JM. Interaction revisited: the difference between two estimates. BMJ. 2003;326(7382):219. https:\/\/doi.org\/10.1136\/bmj.326.7382.219.","journal-title":"BMJ"},{"issue":"7","key":"1992_CR27","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1001\/jamacardio.2020.1624","volume":"5","author":"J Li","year":"2020","unstructured":"Li J, Wang X, Chen J, Zhang H, Deng A. Association of renin-angiotensin system inhibitors with severity or risk of death in patients with hypertension hospitalised for coronavirus disease 2019 (COVID-19) infection in Wuhan, China. JAMA Cardiol. 2020;5(7):825\u201330. https:\/\/doi.org\/10.1001\/jamacardio.2020.1624.","journal-title":"JAMA Cardiol"},{"key":"1992_CR28","doi-asserted-by":"publisher","first-page":"106805","DOI":"10.1016\/j.vph.2020.106805","volume":"135","author":"COVID-19 RISk and Treatments (CORIST) Collaboration","year":"2020","unstructured":"COVID-19 RISk and Treatments (CORIST) Collaboration. 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. https:\/\/doi.org\/10.1016\/j.vph.2020.106805.","journal-title":"Vascul Pharmacol"},{"key":"1992_CR29","doi-asserted-by":"publisher","first-page":"e926651","DOI":"10.12659\/MSM.926651","volume":"26","author":"Z Wang","year":"2020","unstructured":"Wang Z, Zhang D, Wang S, Jin Y, Huan J, Wu Y, et al. A retrospective study from 2 centers in China on the effects of continued use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in patients with hypertension and COVID-19. Med Sci Monit. 2020;26:e926651. https:\/\/doi.org\/10.12659\/MSM.926651.","journal-title":"Med Sci Monit"},{"issue":"10","key":"1992_CR30","doi-asserted-by":"publisher","first-page":"3136","DOI":"10.3390\/jcm9103136","volume":"9","author":"E Rodilla","year":"2020","unstructured":"Rodilla E, Saura A, Jim\u00e9nez I, Mendiz\u00e1bal A, Pineda-Cantero A, Lorenzo-Hern\u00e1ndez E, et al. Association of hypertension with all-cause mortality among hospitalised patients with COVID-19. J Clin Med. 2020;9(10):3136. https:\/\/doi.org\/10.3390\/jcm9103136.","journal-title":"J Clin Med"},{"issue":"12","key":"1992_CR31","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.1093\/ajh\/hpaa149","volume":"33","author":"A Soleimani","year":"2020","unstructured":"Soleimani A, Kazemian S, Karbalai Saleh S, Aminorroaya A, Shajari Z, Hadadi A, et al. Effects of angiotensin receptor blockers (ARBs) on in-hospital outcomes of patients with hypertension and confirmed or clinically suspected COVID-19. Am J Hypertens. 2020;33(12):1102\u201311. https:\/\/doi.org\/10.1093\/ajh\/hpaa149.","journal-title":"Am J Hypertens"},{"issue":"11","key":"1992_CR32","doi-asserted-by":"publisher","first-page":"1974","DOI":"10.1111\/jch.14038","volume":"22","author":"R Chen","year":"2020","unstructured":"Chen R, Yang J, Gao X, Ding X, Yang Y, Shen Y, et al. Influence of blood pressure control and application of renin-angiotensin-aldosterone system inhibitors on the outcomes in COVID-19 patients with hypertension. J Clin Hypertens (Greenwich). 2020;22(11):1974\u201383. https:\/\/doi.org\/10.1111\/jch.14038.","journal-title":"J Clin Hypertens (Greenwich)"},{"issue":"2","key":"1992_CR33","doi-asserted-by":"publisher","first-page":"e15","DOI":"10.1161\/HYPERTENSIONAHA.120.15622","volume":"76","author":"F Zhou","year":"2020","unstructured":"Zhou F, Liu YM, Xie J, Li H, Lei F, Yang H, et al. Comparative impacts of ACE (angiotensin-converting enzyme) inhibitors versus angiotensin II receptor blockers on the risk of COVID-19 mortality. Hypertension. 2020;76(2):e15\u20137. https:\/\/doi.org\/10.1161\/HYPERTENSIONAHA.120.15622.","journal-title":"Hypertension"},{"issue":"1","key":"1992_CR34","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1080\/22221751.2020.1746200","volume":"9","author":"J Meng","year":"2020","unstructured":"Meng J, Xiao G, Zhang J, He X, Ou M, Bi J, et al. Renin-angiotensin system inhibitors improve the clinical outcomes of COVID-19 patients with hypertension. Emerg Microbes Infect. 2020;9(1):757\u201360. https:\/\/doi.org\/10.1080\/22221751.2020.1746200.","journal-title":"Emerg Microbes Infect"},{"key":"1992_CR35","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.59177","volume":"9","author":"MR Garvin","year":"2020","unstructured":"Garvin MR, Alvarez C, Miller JI, Prates ET, Walker AM, Amos BK, et al. A mechanistic model and therapeutic interventions for COVID-19 involving a RAS-mediated bradykinin storm. Elife. 2020;9:e59177. https:\/\/doi.org\/10.7554\/eLife.59177.","journal-title":"Elife"},{"key":"1992_CR36","doi-asserted-by":"publisher","unstructured":"van de Veerdonk F, Netea MG, van Deuren M, van der Meer JW, de Mast Q, Bruggemann RJ, et al. Kinins and cytokines in COVID-19: a comprehensive pathophysiological approach. Preprints. 2020:2020040023. https:\/\/doi.org\/10.20944\/preprints202004.0023.v1.","DOI":"10.20944\/preprints202004.0023.v1"}],"container-title":["BMC Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12916-021-01992-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12916-021-01992-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12916-021-01992-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,2]],"date-time":"2021-06-02T04:07:48Z","timestamp":1622606868000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcmedicine.biomedcentral.com\/articles\/10.1186\/s12916-021-01992-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,12]]},"references-count":36,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["1992"],"URL":"https:\/\/doi.org\/10.1186\/s12916-021-01992-9","relation":{},"ISSN":["1741-7015"],"issn-type":[{"value":"1741-7015","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,12]]},"assertion":[{"value":"31 January 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 April 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 May 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The present study was an extension of a previous study approved by the Ethics Research Committee of the University Hospital \u201cPr\u00edncipe de Asturias\u201d on March 18, 2020 (#SRAA-COVID19), including a waiver for the informed consent []. The Ethics Research Committee was informed of this extension, and no additional ethical assessment was required. Data extracted were fully anonymised and no attempt was made to interview patients or relatives. The study complied with the provisions of the European and Spanish legislation: Order SAS\/3470\/2009, December 16 and Regulation (EU) 2016\/679 of the European Parliament and of the Council of 27 April 2016.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"118"}}