{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:39:34Z","timestamp":1787020774450,"version":"build-2736575974"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T00:00:00Z","timestamp":1713398400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T00:00:00Z","timestamp":1713398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Crit Care"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blockers (ARB) medications are widely prescribed. We sought to assess how pre-admission use of these medications might impact the response to angiotensin-II treatment during vasodilatory shock.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In a\n                      <jats:italic>post-hoc<\/jats:italic>\n                      subgroup analysis of the randomized, placebo-controlled, Angiotensin Therapy for High Output Shock (ATHOS-3) trial, we compared patients with chronic angiotensin-converting enzyme inhibitor (ACEi) use, and patients with angiotensin receptor blocker (ARB) use, to patients without exposure to either ACEi or ARB. The primary outcome was mean arterial pressure after 1-h of treatment. Additional clinical outcomes included mean arterial pressure and norepinephrine equivalent dose requirements over time, and study-drug dose over time. Biological outcomes included baseline RAS biomarkers (renin, angiotensin-I, angiotensin-II, and angiotensin-I\/angiotensin-II ratio), and the change in renin from 0 to 3\u00a0h.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We included n\u2009=\u2009321 patients, of whom, 270 were ACEi and ARB-unexposed, 29 were ACEi-exposed and 22 ARB-exposed. In ACEi\/ARB-unexposed patients, angiotensin-treated patients, compared to placebo, had higher hour-1 mean arterial pressure (9.1\u00a0mmHg [95% CI 7.6\u201310.1],\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001), lower norepinephrine equivalent dose over 48-h (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0037), and lower study-drug dose over 48-h (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). ACEi-exposed patients treated with angiotensin-II showed similarly higher hour-1 mean arterial pressure compared to ACEi\/ARB-unexposed (difference in treatment-effect: \u2212\u20092.2\u00a0mmHg [95% CI \u2212\u20097.0\u20132.6], p\n                      <jats:sub>interaction<\/jats:sub>\n                      \u2009=\u20090.38), but a greater reduction in norepinephrine equivalent dose (p\n                      <jats:sub>interaction<\/jats:sub>\n                      \u2009=\u20090.0031) and study-drug dose (p\n                      <jats:sub>interaction<\/jats:sub>\n                      \u2009&lt;\u20090.0001) over 48-h. In contrast, ARB-exposed patients showed an attenuated effect of angiotensin-II on hour-1 mean arterial pressure versus ACEi\/ARB-unexposed (difference in treatment-effect: \u2212\u20096.0\u00a0mmHg [95% CI \u2212\u200911.5 to \u2212\u20090.6], p\n                      <jats:sub>interaction<\/jats:sub>\n                      \u2009=\u20090.0299), norepinephrine equivalent dose (p\n                      <jats:sub>interaction<\/jats:sub>\n                      \u2009&lt;\u20090.0001), and study-drug dose (p\n                      <jats:sub>interaction<\/jats:sub>\n                      \u2009=\u20090.0008). Baseline renin levels and angiotensin-I\/angiotensin-II ratios were highest in ACEi-exposed patients. Finally, angiotensin-II treatment reduced hour-3 renin in ACEi\/ARB-unexposed and ACEi-exposed patients but not in ARB-exposed patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In vasodilatory shock patients, the cardiovascular and biological RAS response to angiotensin-II differed based upon prior exposure to ACEi and ARB medications. ACEi-exposure was associated with increased angiotensin II responsiveness, whereas ARB-exposure was associated with decreased responsiveness. These findings have clinical implications for patient selection and dosage of angiotensin II in vasodilatory shock.<\/jats:p>\n                    <jats:p>\n                      <jats:italic>Trial Registration<\/jats:italic>\n                      ClinicalTrials.Gov Identifier: NCT 02338843 (Registered January 14th 2015).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13054-024-04910-6","type":"journal-article","created":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T13:01:36Z","timestamp":1713445296000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["ACE inhibitors and angiotensin receptor blockers differentially alter the response to angiotensin II treatment in vasodilatory shock"],"prefix":"10.1186","volume":"28","author":[{"given":"Daniel E.","family":"Leisman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damian R.","family":"Handisides","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence W.","family":"Busse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark C.","family":"Chappell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lakhmir S.","family":"Chawla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Filbin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcia B.","family":"Goldberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kealy R.","family":"Ham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashish K.","family":"Khanna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlies","family":"Ostermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael T.","family":"McCurdy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher D.","family":"Adams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony N.","family":"Hodges","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rinaldo","family":"Bellomo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"The ATHOS-3 Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,18]]},"reference":[{"issue":"9","key":"4910_CR1","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1056\/NEJMoa0907118","volume":"362","author":"D De Backer","year":"2010","unstructured":"De Backer D, Biston P, Devriendt J, et al. 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The respective independent institutional review boards reviewed the protocol, informed-consent form, and all other documents before study initiation.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"DEL, LWB, MCC, MRF, MBG, KRH, AKK, MO, MTC, and RB declare no competing interests. DRH, CDA, and TNH are employees of Innoviva Specialty Therapeutics, of which La Jolla Pharmaceutical Company (LJPC) is a subsidiary. LSC declares that he was formerly an employee of LJPC.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"130"}}