{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T19:04:00Z","timestamp":1790795040988,"version":"4.1.0"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"24","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2016,12,13]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Human or recombinant apolipoprotein A-I (apoA-I) has been shown to increase high-density lipoprotein\u2013mediated cholesterol efflux capacity and to regress atherosclerotic disease in animal and clinical studies. CSL112 is an infusible, plasma-derived apoA-I that has been studied in normal subjects or those with stable coronary artery disease. This study aimed to characterize the safety, tolerability, pharmacokinetics, and pharmacodynamics of CSL112 in patients with a recent acute myocardial infarction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>The AEGIS-I trial (Apo-I Event Reducing in Ischemic Syndromes I) was a multicenter, randomized, double-blind, placebo-controlled, dose-ranging phase 2b trial. Patients with myocardial infarction were stratified by renal function and randomized 1:1:1 to CSL112 (2 g apoA-I per dose) and high-dose CSL112 (6 g apoA-I per dose), or placebo for 4 consecutive weekly infusions. Coprimary safety end points were occurrence of either a hepatic safety event (an increase in alanine transaminase &gt;3 times the upper limit of normal or an increase in total bilirubin &gt;2 times the upper limit of normal) or a renal safety event (an increase in serum creatinine &gt;1.5 times the baseline value or a new requirement for renal replacement therapy).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>A total of 1258 patients were randomized, and 91.2% received all 4 infusions. The difference in incidence rates for an increase in alanine transaminase or total bilirubin between both CSL112 arms and placebo was within the protocol-defined noninferiority margin of 4%. Similarly, the difference in incidence rates for an increase in serum creatinine or a new requirement for renal replacement therapy was within the protocol-defined noninferiority margin of 5%. CSL112 was associated with increases in apoA-I and ex vivo cholesterol efflux similar to that achieved in patients with stable coronary artery disease. In regard to the secondary efficacy end point, the risk for the composite of major adverse cardiovascular events among the groups was similar.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Among patients with acute myocardial infarction, 4 weekly infusions of CSL112 are feasible, well tolerated, and not associated with any significant alterations in liver or kidney function or other safety concern. The ability of CSL112 to acutely enhance cholesterol efflux was confirmed. The potential benefit of CSL112 to reduce major adverse cardiovascular events needs to be assessed in an adequately powered phase 3 trial.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration:<\/jats:title>\n                    <jats:p>\n                      URL:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\">https:\/\/clinicaltrials.gov<\/jats:ext-link>\n                      . Unique identifier: NCT02108262.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.116.025687","type":"journal-article","created":{"date-parts":[[2016,11,16]],"date-time":"2016-11-16T08:20:18Z","timestamp":1479284418000},"page":"1918-1930","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":187,"title":["Safety and Tolerability of CSL112, a Reconstituted, Infusible, Plasma-Derived Apolipoprotein A-I, After Acute Myocardial Infarction"],"prefix":"10.1161","volume":"134","author":[{"given":"C.","family":"Michael Gibson","sequence":"first","affiliation":[{"name":"From PERFUSE Study Group, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical, Harvard Medical School, Boston, MA (C.M.G., S.K., Y.D., M.Y., P.J.); Duke Clinical Research Institute, Cardiovascular Division, Department of Medicine, Duke University Health, Durham, NC (P.T., J.H.A.); INSERM-Unit\u00e9 1148, France Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Bichat, France Universit\u00e9 Paris-Diderot, Sorbonne- Paris Cit\u00e9, France National Heart and Lung Institute, Paris, France (P..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serge","family":"Korjian","sequence":"additional","affiliation":[{"name":"From PERFUSE Study Group, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical, Harvard Medical School, Boston, MA (C.M.G., S.K., Y.D., M.Y., P.J.); Duke Clinical Research Institute, Cardiovascular Division, Department of Medicine, Duke University Health, Durham, NC (P.T., J.H.A.); INSERM-Unit\u00e9 1148, France Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Bichat, France Universit\u00e9 Paris-Diderot, Sorbonne- Paris Cit\u00e9, France National Heart and Lung Institute, Paris, France (P..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierluigi","family":"Tricoci","sequence":"additional","affiliation":[{"name":"From PERFUSE Study Group, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical, Harvard Medical School, Boston, MA (C.M.G., S.K., Y.D., M.Y., P.J.); Duke Clinical Research Institute, Cardiovascular Division, Department of Medicine, Duke University Health, Durham, NC (P.T., J.H.A.); INSERM-Unit\u00e9 1148, France Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Bichat, France Universit\u00e9 Paris-Diderot, Sorbonne- Paris Cit\u00e9, France National Heart and Lung Institute, Paris, France (P..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yazan","family":"Daaboul","sequence":"additional","affiliation":[{"name":"From PERFUSE Study Group, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical, Harvard Medical School, Boston, MA (C.M.G., S.K., Y.D., M.Y., P.J.); Duke Clinical Research Institute, Cardiovascular Division, Department of Medicine, Duke University Health, Durham, NC (P.T., J.H.A.); INSERM-Unit\u00e9 1148, France Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Bichat, France Universit\u00e9 Paris-Diderot, Sorbonne- Paris Cit\u00e9, France National Heart and Lung Institute, Paris, France (P..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Yee","sequence":"additional","affiliation":[{"name":"From PERFUSE Study Group, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical, Harvard Medical School, Boston, MA (C.M.G., S.K., Y.D., M.Y., P.J.); Duke Clinical Research Institute, Cardiovascular Division, Department of Medicine, Duke University Health, Durham, NC (P.T., J.H.A.); INSERM-Unit\u00e9 1148, France Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Bichat, France Universit\u00e9 Paris-Diderot, Sorbonne- Paris Cit\u00e9, France National Heart and Lung Institute, Paris, France (P..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Purva","family":"Jain","sequence":"additional","affiliation":[{"name":"From PERFUSE Study Group, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical, Harvard Medical School, Boston, MA (C.M.G., S.K., Y.D., M.Y., P.J.); Duke Clinical Research Institute, Cardiovascular Division, Department of Medicine, Duke University Health, Durham, NC (P.T., J.H.A.); INSERM-Unit\u00e9 1148, France Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Bichat, France Universit\u00e9 Paris-Diderot, Sorbonne- Paris Cit\u00e9, France National Heart and Lung Institute, Paris, France (P..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John H.","family":"Alexander","sequence":"additional","affiliation":[{"name":"From PERFUSE Study Group, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical, Harvard Medical School, Boston, MA (C.M.G., S.K., Y.D., M.Y., P.J.); Duke Clinical Research Institute, Cardiovascular Division, Department of Medicine, Duke University Health, Durham, NC (P.T., J.H.A.); INSERM-Unit\u00e9 1148, France Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Bichat, France Universit\u00e9 Paris-Diderot, Sorbonne- Paris Cit\u00e9, France National Heart and Lung Institute, Paris, France (P..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. Gabriel","family":"Steg","sequence":"additional","affiliation":[{"name":"From PERFUSE Study Group, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical, Harvard Medical School, Boston, MA (C.M.G., S.K., Y.D., M.Y., P.J.); Duke Clinical Research Institute, Cardiovascular Division, Department of Medicine, Duke University Health, Durham, NC (P.T., J.H.A.); INSERM-Unit\u00e9 1148, France Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Bichat, France Universit\u00e9 Paris-Diderot, Sorbonne- Paris Cit\u00e9, France National Heart and Lung Institute, Paris, France (P..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Michael","family":"Lincoff","sequence":"additional","affiliation":[{"name":"From PERFUSE Study Group, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical, Harvard Medical School, Boston, MA (C.M.G., S.K., Y.D., M.Y., P.J.); Duke Clinical Research Institute, Cardiovascular Division, Department of Medicine, Duke University Health, Durham, NC (P.T., J.H.A.); INSERM-Unit\u00e9 1148, France Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Bichat, France Universit\u00e9 Paris-Diderot, Sorbonne- Paris Cit\u00e9, France National Heart and Lung Institute, Paris, France (P..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.P.","family":"Kastelein","sequence":"additional","affiliation":[{"name":"From PERFUSE Study Group, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical, Harvard Medical School, Boston, MA (C.M.G., S.K., Y.D., M.Y., P.J.); Duke Clinical Research Institute, Cardiovascular Division, Department of Medicine, Duke University Health, Durham, NC (P.T., J.H.A.); INSERM-Unit\u00e9 1148, France Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Bichat, France Universit\u00e9 Paris-Diderot, Sorbonne- Paris Cit\u00e9, France National Heart and Lung Institute, Paris, France (P..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxana","family":"Mehran","sequence":"additional","affiliation":[{"name":"From PERFUSE Study Group, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical, Harvard Medical School, Boston, MA (C.M.G., S.K., Y.D., M.Y., P.J.); Duke Clinical Research Institute, Cardiovascular Division, Department of Medicine, Duke University Health, Durham, NC (P.T., J.H.A.); INSERM-Unit\u00e9 1148, France Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Bichat, France Universit\u00e9 Paris-Diderot, Sorbonne- Paris Cit\u00e9, France National Heart and Lung Institute, Paris, France (P..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise M.","family":"D\u2019Andrea","sequence":"additional","affiliation":[{"name":"From PERFUSE Study Group, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical, Harvard Medical School, Boston, MA (C.M.G., S.K., Y.D., M.Y., P.J.); Duke Clinical Research Institute, Cardiovascular Division, Department of Medicine, Duke University Health, Durham, NC (P.T., J.H.A.); INSERM-Unit\u00e9 1148, France Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Bichat, France Universit\u00e9 Paris-Diderot, Sorbonne- Paris Cit\u00e9, France National Heart and Lung Institute, Paris, France (P..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence I.","family":"Deckelbaum","sequence":"additional","affiliation":[{"name":"From PERFUSE Study Group, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical, Harvard Medical School, Boston, MA (C.M.G., S.K., Y.D., M.Y., P.J.); Duke Clinical Research Institute, Cardiovascular Division, Department of Medicine, Duke University Health, Durham, NC (P.T., J.H.A.); INSERM-Unit\u00e9 1148, France Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Bichat, France Universit\u00e9 Paris-Diderot, Sorbonne- Paris Cit\u00e9, France National Heart and Lung Institute, Paris, France (P..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bela","family":"Merkely","sequence":"additional","affiliation":[{"name":"From PERFUSE Study Group, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical, Harvard Medical School, Boston, MA (C.M.G., S.K., Y.D., M.Y., P.J.); Duke Clinical Research Institute, Cardiovascular Division, Department of Medicine, Duke University Health, Durham, NC (P.T., J.H.A.); INSERM-Unit\u00e9 1148, France Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Bichat, France Universit\u00e9 Paris-Diderot, Sorbonne- Paris Cit\u00e9, France National Heart and Lung Institute, Paris, France (P..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maciej","family":"Zarebinski","sequence":"additional","affiliation":[{"name":"From PERFUSE Study Group, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical, Harvard Medical School, Boston, MA (C.M.G., S.K., Y.D., M.Y., P.J.); Duke Clinical Research Institute, Cardiovascular Division, Department of Medicine, Duke University Health, Durham, NC (P.T., J.H.A.); INSERM-Unit\u00e9 1148, France Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Bichat, France Universit\u00e9 Paris-Diderot, Sorbonne- Paris Cit\u00e9, France National Heart and Lung Institute, Paris, France (P..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ton Oude","family":"Ophuis","sequence":"additional","affiliation":[{"name":"From PERFUSE Study Group, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical, Harvard Medical School, Boston, MA (C.M.G., S.K., Y.D., M.Y., P.J.); Duke Clinical Research Institute, Cardiovascular Division, Department of Medicine, Duke University Health, Durham, NC (P.T., J.H.A.); INSERM-Unit\u00e9 1148, France Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Bichat, France Universit\u00e9 Paris-Diderot, Sorbonne- Paris Cit\u00e9, France National Heart and Lung Institute, Paris, France (P..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Harrington","sequence":"additional","affiliation":[{"name":"From PERFUSE Study Group, Cardiovascular Division, Department of Medicine, Beth Israel Deaconess Medical, Harvard Medical School, Boston, MA (C.M.G., S.K., Y.D., M.Y., P.J.); Duke Clinical Research Institute, Cardiovascular Division, Department of Medicine, Duke University Health, Durham, NC (P.T., J.H.A.); INSERM-Unit\u00e9 1148, France Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Bichat, France Universit\u00e9 Paris-Diderot, Sorbonne- Paris Cit\u00e9, France National Heart and Lung Institute, Paris, France (P..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.38985.646481.55"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1002358"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2011.02.332"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-8703(91)90861-B"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.320.7236.671"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.83.1.356"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-55-1-33"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/hc0302.102575"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyh405"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0195-668X(03)00114-3"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.2006.108167"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.39261.471806.55"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1300955"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0706628"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1107579"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1206797"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehu171"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1409065"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(15)00126-6"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1097\/HCO.0000000000000211"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehu105"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2014.09.001"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.114.303454"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.113.301981"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.194"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.114.303720"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.115.002171"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/jat.3264"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.297.15.jpc70004"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2012.08.001"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2016.06.017"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehp399"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1107579"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.2165\/11631530-000000000-00000"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-1241.2008.01938.x"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)61383-4"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2015.09.013"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.308685"}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCULATIONAHA.116.025687","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T02:53:04Z","timestamp":1715568784000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCULATIONAHA.116.025687"}},"subtitle":["The AEGIS-I Trial (ApoA-I Event Reducing in Ischemic Syndromes I)"],"short-title":[],"issued":{"date-parts":[[2016,12,13]]},"references-count":38,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2016,12,13]]}},"alternative-id":["10.1161\/CIRCULATIONAHA.116.025687"],"URL":"https:\/\/doi.org\/10.1161\/circulationaha.116.025687","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,12,13]]},"assertion":[{"value":"2016-09-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-10-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-11-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}