{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T22:14:02Z","timestamp":1791670442252,"version":"4.3.4"},"reference-count":23,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,1,12]],"date-time":"2022-01-12T00:00:00Z","timestamp":1641945600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008322","name":"CSL Behring","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Cardiology"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Despite low\u2010density lipoprotein cholesterol\u2010lowering therapies and other standard\u2010of\u2010care therapy, there remains a substantial residual atherosclerotic risk among patients with an acute coronary syndrome (ACS). This study aims to estimate the risk of early and late recurrent major adverse cardiovascular events (MACE) and address its implications on trial design.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A literature search was performed to collect phase III interventional trials on high\u2010risk ACS patients. Pooled event rates at 90 and 360\u2009days were estimated by fitting random\u2010effects models using the DerSimonian\u2013Laird method. Under the assumption of a total sample size of 10,000 and 1:1 allocation at a one\u2010sided alpha of 0.025 using the log\u2010rank test, the relationship between power and relative risk reduction (RRR) or absolute risk reduction (ARR) was explored for early versus late MACE endpoint.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Seven trials representing 82,727 recent ACS patients were analyzed. The pooled rates of recurrent MACE were 4.1% and 8.3% at 90 and 360\u2009days. Approximately 49% of events occurred within the first 90\u2009days. Based on the estimated risks at 90 and 360\u2009days, to attain 90% statistical power, a lower magnitude of RRR is required for late MACE than early MACE (22% vs. 30%), whereas a lower magnitude of ARR is required for early MACE than late MACE (1.2% vs. 1.8%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The initial 90\u2010day window after ACS represents a vulnerable period for recurrent events. From a trial design perspective, determining a clinically important benefit by RRR versus ARR may influence the decision between early and late MACE as the study endpoint.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/clc.23773","type":"journal-article","created":{"date-parts":[[2022,1,12]],"date-time":"2022-01-12T06:49:47Z","timestamp":1641970187000},"page":"299-307","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Early and late recurrent cardiovascular events among high\u2010risk patients with an acute coronary syndrome: Meta\u2010analysis of phase III studies and implications on trial design"],"prefix":"10.1002","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8371-1689","authenticated-orcid":false,"given":"Gerald","family":"Chi","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane J.","family":"Lee","sequence":"additional","affiliation":[{"name":"Baim Institute for Clinical Research Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed H. A.","family":"Kazmi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Fitzgerald","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahar","family":"Memar Montazerin","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arzu","family":"Kalayci","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serge","family":"Korjian","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Heise","sequence":"additional","affiliation":[{"name":"CSL Behring King of Prussia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence I.","family":"Deckelbaum","sequence":"additional","affiliation":[{"name":"CSL Behring King of Prussia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Libby","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Brigham and Women's Hospital Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak L.","family":"Bhatt","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Brigham and Women's Hospital Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Michael","family":"Gibson","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,1,12]]},"reference":[{"issue":"25","key":"e_1_2_10_2_1","first-page":"e1082","article-title":"2018 AHA\/ACC\/AACVPR\/AAPA\/ABC\/ACPM\/ADA\/AGS\/APhA\/ASPC\/NLA\/PCNA guideline on the management of blood cholesterol: A report of the American College of Cardiology\/American Heart Association Task Force on Clinical Practice Guidelines","volume":"139","author":"Grundy SM","year":"2019","journal-title":"Circulation"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11883-011-0219-7"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.181940"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chb.2015.09.008"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.d5928"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0706482"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0904327"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1112277"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1205512"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1305889"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.3321"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.11061"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61368-4"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2007.10.038"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.117.007402"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-153-12-201012210-00006"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(19)30003-8"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/eht571"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60312-2"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.299.21.2524"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-1342"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-0450"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2017.2922"}],"container-title":["Clinical Cardiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/clc.23773","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/clc.23773","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/clc.23773","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,27]],"date-time":"2023-08-27T03:03:15Z","timestamp":1693105395000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/clc.23773"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,12]]},"references-count":23,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,3]]}},"alternative-id":["10.1002\/clc.23773"],"URL":"https:\/\/doi.org\/10.1002\/clc.23773","archive":["Portico"],"relation":{},"ISSN":["0160-9289","1932-8737"],"issn-type":[{"value":"0160-9289","type":"print"},{"value":"1932-8737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,12]]},"assertion":[{"value":"2021-09-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-12-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}