{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T03:14:26Z","timestamp":1793502866127,"version":"4.5.0"},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"19","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2025,10,7]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Calcific aortic valve stenosis (CAVS) can lead to cardiac adverse outcomes; however, currently, no effective pharmacological interventions are available to prevent or delay disease progression. Emerging evidence has identified significant associations between CAVS and key biomarkers, including Lp(a) (lipoprotein [a]), low\u2010density lipoprotein cholesterol, and PCSK9 (proprotein convertase subtilisin\/kexin type 9). However, robust evidence from randomized controlled trials is still lacking to substantiate these associations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">The EPISODE (Effect of PCSK9 Inhibitors on Calcific Aortic Valve Stenosis) trial is a prospective, evaluator\u2010blinded, randomized controlled trial designed to assess the therapeutic efficacy of PCSK9 inhibitors in patients with CAVS. A total of 160 patients with mild\u2010to\u2010moderate or asymptomatic severe CAVS will be randomly assigned to receive either statin monotherapy or a combination of statins and PCSK9 inhibitors. Participants will undergo follow\u2010up assessments at 3\u2010month intervals for 24\u2009months, including transthoracic ultrasonic cardiogram, computed tomography, and quality\u2010of\u2010life evaluations using the EuroQol\u20105 Dimension\u20103 Level questionnaire. The primary end point is the annualized change in peak aortic jet velocity, whereas secondary end points encompass changes in aortic valve area, calcification score, incidence of heart valve surgery, and quality of life. Safety end points include all\u2010cause mortality and cardiovascular events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">The trial aims to evaluate the efficacy of PCSK9 inhibitors in modulating disease progression, reducing adverse cardiovascular events, and improving clinical outcomes in patients with CAVS. The anticipated findings are expected to provide critical insights for developing novel therapeutic strategies for early intervention in CAVS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Registration<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      URL:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      ; Unique Identifier: NCT04968509.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.042112","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T11:15:22Z","timestamp":1758280522000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":12,"title":["Rationale and Design of the EPISODE Trial: A Randomized Controlled Trial on the Effect of PCSK9 Inhibitors in Calcific Aortic Valve Stenosis"],"prefix":"10.1161","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-4787-1543","authenticated-orcid":false,"given":"Yang","family":"Zheng","sequence":"first","affiliation":[{"name":"Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuxuan","family":"Li","sequence":"additional","affiliation":[{"name":"Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxiu","family":"Yang","sequence":"additional","affiliation":[{"name":"Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5338-651X","authenticated-orcid":false,"given":"Jingyao","family":"Yang","sequence":"additional","affiliation":[{"name":"Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3412-2335","authenticated-orcid":false,"given":"Zaiqiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4806-6458","authenticated-orcid":false,"given":"Xiaoteng","family":"Ma","sequence":"additional","affiliation":[{"name":"Capital Medical University","place":["Beijing, China"]},{"name":"Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7516-7038","authenticated-orcid":false,"given":"Zhijian","family":"Wang","sequence":"additional","affiliation":[{"name":"Capital Medical University","place":["Beijing, China"]},{"name":"Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.6"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12872-021-02154-8"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.02.057"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.006767"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/eci.13527"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa043876"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0804602"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.900027"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2020.11.018"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2020.06.009"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2020.06.001"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pcad.2020.06.002"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2020.05.004"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1109034"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2019.01.070"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2015.07.020"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2018.3798"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2020.0728"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.09.063"},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12265-021-10138-4"},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2016-1206"},{"key":"e_1_3_1_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.037184"},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2020.06.004"},{"key":"e_1_3_1_25_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1615664"},{"key":"e_1_3_1_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2006.07.072"},{"key":"e_1_3_1_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2022.02.005"},{"key":"e_1_3_1_28_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000001254"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.125.042112","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T09:33:46Z","timestamp":1759916026000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.125.042112"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,7]]},"references-count":27,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2025,10,7]]}},"alternative-id":["10.1161\/JAHA.125.042112"],"URL":"https:\/\/doi.org\/10.1161\/jaha.125.042112","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,7]]},"assertion":[{"value":"2025-03-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e042112"}}