{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T23:52:42Z","timestamp":1790466762344,"version":"4.1.0"},"reference-count":53,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,5,10]],"date-time":"2020-05-10T00:00:00Z","timestamp":1589068800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005595","name":"University of California","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005595","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:p>\n                    Concerns have been raised regarding the safety of angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in patients with coronavirus disease of 2019 (COVID\u201019), based on the hypothesis that such medications may raise expression of ACE2, the receptor for severe acute respiratory syndrome\u2010coronavirus 2\u00a0(SARS\u2010CoV\u20102). We conducted a literature review of studies (\n                    <jats:italic>n\u00a0<\/jats:italic>\n                    =\u00a012) in experimental animals and human subjects (\n                    <jats:italic>n\u00a0<\/jats:italic>\n                    =\u00a012) and evaluated the evidence regarding the impact of administration of ACEIs and ARBs on ACE2 expression. We prioritized studies that assessed ACE2 protein expression data, measured directly or inferred from ACE2 activity assays. The findings in animals are inconsistent with respect to an increase in ACE2 expression in response to treatment with ACEIs or ARBs. Control\/sham animals show little to no effect in the plurality of studies. Those studies that report increases in ACE2 expression tend to involve acute injury models and\/or higher doses of ACEIs or ARBs than are typically administered to patients. Data from human studies overwhelmingly imply that administration of ACEIs\/ARBs does not increase ACE2 expression. Available evidence, in particular, data from human studies, does not support the hypothesis that ACEI\/ARB use increases ACE2 expression and the risk of complications from COVID\u201019. We conclude that patients being treated with ACEIs and ARBs should continue their use for approved indications.\n                  <\/jats:p>","DOI":"10.1002\/cpt.1863","type":"journal-article","created":{"date-parts":[[2020,4,22]],"date-time":"2020-04-22T15:25:54Z","timestamp":1587569154000},"page":"236-241","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":106,"title":["Risks of ACE Inhibitor and ARB Usage in COVID\u201019: Evaluating the Evidence"],"prefix":"10.1111","volume":"108","author":[{"given":"Krishna","family":"Sriram","sequence":"first","affiliation":[{"name":"Department of Pharmacology University of California San Diego La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A.","family":"Insel","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of California San Diego La Jolla California USA"},{"name":"Department of Medicine University of California San Diego La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,5,10]]},"reference":[{"key":"e_1_2_6_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(20)30116-8"},{"key":"e_1_2_6_2_1","volume-title":"HFSA\/ACC\/AHA Statement Addresses Concerns Re: Using RAAS Antagonists in COVID\u201019","author":"Bozkurt B.","year":"2020"},{"key":"e_1_2_6_3_1","first-page":"m406","article-title":"Rapid response: use of angiotensin receptor blockers such as Telmisartan, Losartsan in nCoV Wuhan Corona Virus infections\u2014novel mode of treatment. Response to the emerging novel coronavirus outbreak","volume":"368","author":"Phadke M.","year":"2020","journal-title":"BMJ"},{"key":"e_1_2_6_4_1","unstructured":"Lewis E.ACE\u2010inhibitors ARBs and COVID\u201019: what GPs need to know. Royal Australian College of General Practitioners (RACGP) Feature March 18 2020 (2020)."},{"key":"e_1_2_6_5_1","article-title":"COVID\u201019 and angiotensin\u2010converting enzyme inhibitors and angiotensin receptor blockers: what is the evidence?","author":"Patel A.B.","journal-title":"JAMA"},{"key":"e_1_2_6_6_1","article-title":"Renin\u2013angiotensin\u2013aldosterone system inhibitors in patients with Covid\u201019","author":"Vaduganathan M.","journal-title":"N. Engl. J. Med."},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41440-020-0433-1"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1260419"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000185629"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2005.00675.x"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.acvd.2013.01.004"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.4103\/0976-0105.177703"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.2987"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0000000000000302"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000237862.94083.45"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2007.041855"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2010.02.009"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2011.063156"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20120162"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2016.2737"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20090318"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0b013e32834f04b6"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1159\/000368486"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajh\/hpu086"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfv025"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.1670"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.02.058"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2179-y"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2005.09.038"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1159\/000318607"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2017.06.005"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30566-3"},{"key":"e_1_2_6_33_1","article-title":"Anti\u2010hypertensive angiotensin II receptor blockers associated to mitigation of disease severity in elderly COVID\u201019 patients","author":"Liu Y.","journal-title":"medRxiv"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.120.317134"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2020.1746200"},{"key":"e_1_2_6_36_1","article-title":"Renin\u2010angiotensin system blockers and the COVID\u201019 pandemic: at present there is no evidence to abandon renin\u2010angiotensin system blockers","author":"Danser A.J.","journal-title":"Hypertension"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.4077\/CJP.2014.BAD268"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jhh.1000991"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1080\/13880209.2016.1190762"},{"key":"e_1_2_6_40_1","unstructured":"Stockbridge N.NDA 204308 Center for drug evaluation and research<https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2013\/204308Orig1s000MedR.pdf> (2013)."},{"key":"e_1_2_6_41_1","first-page":"2162","article-title":"The effect of candesartan on the pharmacokinetics of enalaprilat in nephrotic rats","volume":"16","author":"Bi B.T.","year":"2012","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200241030-00005"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.2133\/dmpk.DMPK-11-RG-089"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.3797\/scipharm.1410-15"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.3109\/03602538409041080"},{"key":"e_1_2_6_46_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2019\/7537618","article-title":"A high throughput HPLC\u2010MS\/MS method for antihypertensive drugs determination in plasma and its application on pharmacokinetic interaction study with Shuxuetong injection in rats","volume":"2019","author":"Wei J.","year":"2019","journal-title":"BioMed Res. Int."},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1797.2011.01467.x"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11255-016-1334-8"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2008.02.088"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0061695"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1177\/1470320316668435"},{"key":"e_1_2_6_52_1","first-page":"1280","article-title":"Angiotensin converting enzyme 2 activity and human atrial fibrillation: increased plasma angiotensin converting enzyme 2 activity is associated with atrial fibrillation and more advanced left atrial structural remodelling","volume":"19","author":"Walters T.E.","year":"2017","journal-title":"Ep. Europace"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0198144"}],"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcpt.1863","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.1863","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpt.1863","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.1863","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T08:37:46Z","timestamp":1699346266000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/cpt.1863"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,10]]},"references-count":53,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,8]]}},"alternative-id":["10.1002\/cpt.1863"],"URL":"https:\/\/doi.org\/10.1002\/cpt.1863","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.03.25.20043927","asserted-by":"object"}]},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,10]]},"assertion":[{"value":"2020-04-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}