{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T17:09:10Z","timestamp":1775149750803,"version":"3.50.1"},"reference-count":17,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T00:00:00Z","timestamp":1722297600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Cardiology"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>The COVID\u201019 pandemic disrupted clinical research. CLEAR\u00a0Outcomes investigated the effect of bempedoic acid (BA) versus placebo in 13\u2009970 patients with statin intolerance and high cardiovascular (CV) risk. BA reduced the risk of the primary endpoint (composite of CV death, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization) by 13%. CLEAR\u00a0Outcomes began before\u00a0and continued for 2.7 years after\u00a0the start of the pandemic.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The impact of the COVID\u201019 pandemic on patient disposition, adverse events, and major adverse CV events (MACE) in CLEAR\u00a0Outcomes was assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Rates of severe infection, hospitalization, or first MACE associated with a positive COVID\u201019 test were low and balanced between treatment groups. Rates of all\u2010cause death, non\u2010CV death, and undetermined death increased in the pandemic period compared with the pre\u2010pandemic period, while rates of CV death with a known etiology remained stable. A sensitivity analysis excluding undetermined deaths occurring after the onset of the pandemic from the CV death designation yielded hazard ratios of 0.84 (95% CI, 0.76\u20130.93) for the primary endpoint and 0.94 (95% CI, 0.76\u20131.16) for the secondary endpoint of CV death, compared with 0.87 (95% CI, 0.79\u20130.96) and 1.04 (95% CI, 0.88\u20131.24), respectively, in the original analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The CLEAR Outcomes trial continued uninterrupted throughout the COVID\u201019 pandemic. Certain trial endpoints may have been impacted by the pandemic. Specifically, the classification of undetermined deaths as CV deaths may have attenuated the effect of BA on key efficacy endpoints.<\/jats:p><\/jats:sec>","DOI":"10.1002\/clc.24328","type":"journal-article","created":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T09:49:38Z","timestamp":1722332978000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Impact of the COVID\u201019 Pandemic on Conduct and Results of CLEAR Outcomes Trial"],"prefix":"10.1002","volume":"47","author":[{"given":"Abhayjit","family":"Singh","sequence":"first","affiliation":[{"name":"Section of Preventive Cardiology and Rehabilitation, Department of Cardiovascular Medicine Cleveland Clinic Foundation  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3262-792X","authenticated-orcid":false,"given":"Luke J.","family":"Laffin","sequence":"additional","affiliation":[{"name":"Section of Preventive Cardiology and Rehabilitation, Department of Cardiovascular Medicine Cleveland Clinic Foundation  Cleveland Ohio USA"},{"name":"Cleveland Clinic Coordinating Center for Clinical Research (C5Research)  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashish","family":"Sarraju","sequence":"additional","affiliation":[{"name":"Section of Preventive Cardiology and Rehabilitation, Department of Cardiovascular Medicine Cleveland Clinic Foundation  Cleveland Ohio USA"},{"name":"Cleveland Clinic Coordinating Center for Clinical Research (C5Research)  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Michael Lincoff","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Coordinating Center for Clinical Research (C5Research)  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9668-4368","authenticated-orcid":false,"given":"Stephen J.","family":"Nicholls","sequence":"additional","affiliation":[{"name":"Victorian Heart Institute Monash University  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"LeAnne","family":"Bloedon","sequence":"additional","affiliation":[{"name":"Esperion Therapeutics\u00a0Inc. Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William J.","family":"Sasiela","sequence":"additional","affiliation":[{"name":"Esperion Therapeutics\u00a0Inc. Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na","family":"Li","sequence":"additional","affiliation":[{"name":"Esperion Therapeutics\u00a0Inc. Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula","family":"Robinson","sequence":"additional","affiliation":[{"name":"Esperion Therapeutics\u00a0Inc. Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie","family":"Kelly","sequence":"additional","affiliation":[{"name":"Esperion Therapeutics\u00a0Inc. Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denise","family":"Mason","sequence":"additional","affiliation":[{"name":"Cleveland Clinic Coordinating Center for Clinical Research (C5Research)  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven E.","family":"Nissen","sequence":"additional","affiliation":[{"name":"Section of Preventive Cardiology and Rehabilitation, Department of Cardiovascular Medicine Cleveland Clinic Foundation  Cleveland Ohio USA"},{"name":"Cleveland Clinic Coordinating Center for Clinical Research (C5Research)  Cleveland Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,7,30]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/d41573-020-00150-9"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2215024"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)02796-3"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13063-021-05219-3"},{"key":"e_1_2_9_6_1","volume-title":"Conduct of Clinical Trials of Medical Products During the COVID\u201019 Public Health Emergency: Guidance for Industry, Investigators, and Institutional Review Boards U.S. Department of Health and Human Services","author":"Food and Drug Administration,\u00a0","year":"2021"},{"key":"e_1_2_9_7_1","volume-title":"COVID\u201019 Guidance: Research and Development","author":"European Medicines Agency,\u00a0","year":"2020"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2020.07.051"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13063-023-07277-1"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1410489"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1615664"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1801174"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.037202"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n1437"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05522-2"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-21844-7"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2021.06.911"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.033502"}],"container-title":["Clinical Cardiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/clc.24328","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T03:48:08Z","timestamp":1724816888000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/clc.24328"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,30]]},"references-count":17,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2024,8]]}},"alternative-id":["10.1002\/clc.24328"],"URL":"https:\/\/doi.org\/10.1002\/clc.24328","archive":["Portico"],"relation":{},"ISSN":["0160-9289","1932-8737"],"issn-type":[{"value":"0160-9289","type":"print"},{"value":"1932-8737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,30]]},"assertion":[{"value":"2024-05-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e24328"}}