{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T02:30:16Z","timestamp":1777343416063,"version":"3.51.4"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"24","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2021,12,21]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Use of angiotensin\u2010converting enzyme inhibitors and angiotensin receptor blockers (ACEi\/ARB) is thought to affect COVID\u201019 through modulating levels of angiotensin\u2010converting enzyme 2, the cell entry receptor for SARS\u2010CoV2. We sought to assess the association between ACEi\/ARB, biomarkers of inflammation, and outcomes in patients hospitalized for COVID\u201019.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">We leveraged the ISIC (International Study of Inflammation in COVID\u201019), identified patients admitted for symptomatic COVID\u201019 between February 1, 2020 and June 1, 2021 for COVID\u201019, and examined the association between in\u2010hospital ACEi\/ARB use and all\u2010cause death, need for ventilation, and need for dialysis. We estimated the causal effect of ACEi\/ARB on the composite outcomes using marginal structural models accounting for serial blood pressure and serum creatinine measures. Of 2044 patients in ISIC, 1686 patients met inclusion criteria, of whom 398 (23.6%) patients who were previously on ACEi\/ARB received at least 1 dose during their hospitalization for COVID\u201019. There were 215 deaths, 407 patients requiring mechanical ventilation, and 124 patients who required dialysis during their hospitalization. Prior ACEi\/ARB use was associated with lower levels of soluble urokinase plasminogen activator receptor and C\u2010reactive protein. In multivariable analysis, in\u2010hospital ACEi\/ARB use was associated with a lower risk of the composite outcome of in\u2010hospital death, mechanical ventilation, or dialysis (adjusted hazard ratio 0.49, 95% CI [0.36\u20130.65]).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">In patients hospitalized for COVID\u201019, ACEi\/ARB use was associated with lower levels of inflammation and lower risk of in\u2010hospital outcomes. Clinical trials will define the role of ACEi\/ARB in the treatment of COVID\u201019.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Registration<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              ; Unique identifier: NCT04818866.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.121.023535","type":"journal-article","created":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T11:47:50Z","timestamp":1639136870000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":27,"title":["Angiotensin\u2010Converting Enzyme Inhibitors, Angiotensin II Receptor Blockers, and Outcomes in Patients Hospitalized for COVID\u201019"],"prefix":"10.1161","volume":"10","author":[{"given":"Michael","family":"Pan","sequence":"first","affiliation":[{"name":"Department of Internal Medicine University of Michigan Ann Arbor MI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexi","family":"Vasbinder","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Michigan Ann Arbor MI"},{"name":"Division of Cardiology Department of Internal Medicine University of Michigan Ann Arbor MI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Anderson","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Internal Medicine University of Michigan Ann Arbor MI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toniemarie","family":"Catalan","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Internal Medicine University of Michigan Ann Arbor MI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Husam R.","family":"Shadid","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Michigan Ann Arbor MI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9801-3517","authenticated-orcid":false,"given":"Hanna","family":"Berlin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Michigan Ann Arbor MI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kishan","family":"Padalia","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Michigan Ann Arbor MI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"O\u2019Hayer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Michigan Ann Arbor MI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chelsea","family":"Meloche","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Michigan Ann Arbor MI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1506-5099","authenticated-orcid":false,"given":"Tariq U.","family":"Azam","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Internal Medicine University of Michigan Ann Arbor MI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ibrahim","family":"Khaleel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Michigan Ann Arbor MI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8581-1990","authenticated-orcid":false,"given":"Erinleigh","family":"Michaud","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University of Michigan Ann Arbor MI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9677-3010","authenticated-orcid":false,"given":"Pennelope","family":"Blakely","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Internal Medicine University of Michigan Ann Arbor MI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abbas","family":"Bitar","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Internal Medicine University of Michigan Ann Arbor MI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5568-8517","authenticated-orcid":false,"given":"Yiyuan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics School of Public Health University of Michigan Ann Arbor MI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lili","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Biostatistics School of Public Health University of Michigan Ann Arbor MI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rodica","family":"Pop\u2010Busui","sequence":"additional","affiliation":[{"name":"Division of Metabolism, Endocrinology and Diabetes Department of Internal Medicine University of Michigan Ann Arbor MI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sven H.","family":"Loosen","sequence":"additional","affiliation":[{"name":"Clinic for Gastroenterology, Hepatology and Infectious Diseases Medical Faculty University Hospital D\u00fcsseldorf D\u00fcsseldorf Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7634-4665","authenticated-orcid":false,"given":"Athanasios","family":"Chalkias","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology School of Health Sciences Faculty of Medicine University of Thessaly Larisa Greece"},{"name":"Outcomes Research Consortium Cleveland OH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Tacke","sequence":"additional","affiliation":[{"name":"Department of Hepatology &amp; Gastroenterology Campus Charit\u00e9 Mitte\/Campus Virchow\u2010KlinikumCharit\u00e9 University Medicine Berlin Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4713-3911","authenticated-orcid":false,"given":"Evangelos J.","family":"Giamarellos\u2010Bourboulis","sequence":"additional","affiliation":[{"name":"4th Department of Internal Medicine National and Kapodistrian University of Athens Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jochen","family":"Reiser","sequence":"additional","affiliation":[{"name":"Department of Medicine Rush University Medical Center Chicago IL"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4630-4275","authenticated-orcid":false,"given":"Jesper","family":"Eugen\u2010Olsen","sequence":"additional","affiliation":[{"name":"Department of Clinical Research Copenhagen University Hospital Amager and Hvidovre Hvidovre Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0180-349X","authenticated-orcid":false,"given":"Salim S.","family":"Hayek","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Internal Medicine University of Michigan Ann Arbor MI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"the ISIC Group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","unstructured":"WHO COVID\u201019 Dashboard. World Health Organization; 2020. Available at: https\/\/covid19.who.int\/. Accessed June 30 2021."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2001017"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30251-8"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1267"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00127-20"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature00786"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.87.5.e1"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.116.06591"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.107.102152"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.34.1.118"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1999.0543"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2006.01.059"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1570"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00498.2016"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03712"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-014-1889-6"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000124667.34652.1a"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.104.510461"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.120.317134"},{"key":"e_1_3_2_21_2","doi-asserted-by":"crossref","unstructured":"Yang G Tan Z Zhou L Yang M Peng L Liu J Cai J Yang R Han J Huang Y et al. Angiotensin II receptor blockers and angiotensin\u2010converting enzyme inhibitors usage is associated with improved inflammatory status and clinical outcomes in COVID\u201019 patients with hypertension [Internet]. 2020. doi: 10.1101\/2020.03.31.20038935","DOI":"10.1101\/2020.03.31.20038935"},{"key":"e_1_3_2_22_2","article-title":"Treatment with ACE\u2010inhibitors is associated with less severe disease with SARS\u2010Covid\u201019 infection in a multi\u2010site UK acute Hospital Trust","author":"Bean D","year":"2020","unstructured":"Bean D, Kraljevic Z, Searle T, Bendayan R, Pickles A, Folarin A, Roguski L, Noor K, Shek A, O\u2019gallagher K, et al. Treatment with ACE\u2010inhibitors is associated with less severe disease with SARS\u2010Covid\u201019 infection in a multi\u2010site UK acute Hospital Trust. medRxiv. 2020:2020.04.07.20056788.","journal-title":"medRxiv"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.11301"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2006923"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2008975"},{"key":"e_1_3_2_26_2","article-title":"Association of angiotensin\u2010converting enzyme inhibitors and angiotensin receptor blockers with the risk of hospitalization and death in hypertensive patients with coronavirus disease\u201019","author":"Khera R","year":"2020","unstructured":"Khera R, Clark C, Lu Y, Guo Y, Ren S, Truax B, Spatz ES, Murugiah K, Lin Z, Omer SB, et al. Association of angiotensin\u2010converting enzyme inhibitors and angiotensin receptor blockers with the risk of hospitalization and death in hypertensive patients with coronavirus disease\u201019. medRxiv Prepr Serv Heal Sci. 2020:2020.05.17.20104943.","journal-title":"medRxiv Prepr Serv Heal Sci"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cct.2021.106330"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaa447"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2020.1624"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(20)30558-0"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.25864"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.3594"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001648-200009000-00011"},{"key":"e_1_3_2_34_2","unstructured":"American Heart Association (AHA) Heart Failure Society of America (HFSA) and American College of Cardiology (ACC) Patients taking ACE\u2010I and ARBs who contract COVID\u201019 should continue treatment unless otherwise advised by their physician. 2020. Available at: https:\/\/newsroom.heart.org\/news\/patients\u2010taking\u2010ace\u2010i\u2010and\u2010arbs\u2010who\u2010contract\u2010covid\u201019\u2010should\u2010continue\u2010treatment\u2010unless\u2010otherwise\u2010advised\u2010by\u2010their\u2010physician. Accessed May 5 2021."},{"key":"e_1_3_2_35_2","unstructured":"International Society of Hypertension A statement from the International Society of Hypertension on COVID\u201019. 2020. 22. Available at: https:\/\/ish\u2010world.com\/a\u2010statement\u2010from\u2010the\u2010international\u2010society\u2010of\u2010hypertension\u2010on\u2010covid\u201019\/. Accessed May 5 2021."},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.02.052"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000140265.21608.8E"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.10.050"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.121.023535","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T11:18:37Z","timestamp":1715599117000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.121.023535"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,21]]},"references-count":37,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2021,12,21]]}},"alternative-id":["10.1161\/JAHA.121.023535"],"URL":"https:\/\/doi.org\/10.1161\/jaha.121.023535","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,21]]},"assertion":[{"value":"2021-08-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-12-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e023535"}}